ORCID Profile
0000-0003-3619-7901
Current Organisation
University of South Australia
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Bioprocessing, Bioproduction and Bioproducts | Medicinal and Biomolecular Chemistry | Analytical Biochemistry | Biologically Active Molecules
Nutraceuticals and Functional foods | Service Industries Standards and Calibrations |
Publisher: Equinox Publishing
Date: 03-08-2015
Abstract: As universities in Australia are faced with a growth in ersity and intensity of religion and spirituality on c us, this article explores the work of chaplains and its reception by students on a multi-c us suburban university. It finds that the religious work of these professionals is not the primary emphasis in the university context what is of greater significance to students and the university institution is the broader pastoral and welfare-support role of chaplains. We discuss these findings in relation to post-secularism theory and the scaling down of state-provided welfare in public institutions such as universities.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.EJPS.2018.03.018
Abstract: A novel hybrid microparticulate system composed of poly(lactic-co-glycolic) acid (PLGA) nanoparticles and submicron medium-chain triglyceride (MCT) droplets was fabricated to overcome the pH-dependent solubility and precipitation challenges associated with a model poorly water-soluble weak base, cinnarizine (CIN). Molecular CIN was confined within both the lipid and polymer phase of PLGA-lipid hybrid (PLH) and PLGA-lipid-mannitol hybrid (PLMH) particles, which offered significant biopharmaceutical advantages in comparison to the unformulated drug, submicron MCT droplets and PLGA nanoparticles. This was highlighted by a substantial reduction in the pH-induced precipitation during in vitro gastrointestinal two-step dissolution studies. A >2.5-fold solubilisation enhancement was observed for the composite particles during simulated intestinal conditions, compared to pure CIN. Furthermore, the drug solubilisation capacity during in vitro intestinal digesting conditions was ~2-2.5 times greater for PLMH particles compared to the precursor emulsion droplets and PLGA nanoparticles. The observations from this study indicate that a synergy exists between the degradation products of PLGA nanoparticles and lipid droplets, whereby the dual-phase release and dissolution mechanism of the hybrid particles aids in prolonging pH-provoked precipitation. Subsequently, the ability for PLGA polymers and oligomers to act as polymeric precipitation inhibitors has been highlighted for the first time.
Publisher: American Chemical Society (ACS)
Date: 13-03-2021
Publisher: Inference: International Review of Science
Date: 03-2019
Abstract: In a postindustrial world dominated by science, institutional religion is in decline. Yet social actors are more and more interested in practicing their spirituality by themselves for themselves.
Publisher: British Association for the Study of Religions (BASR)
Date: 16-09-2014
Publisher: Elsevier BV
Date: 05-2023
Publisher: American Chemical Society (ACS)
Date: 22-09-2020
Publisher: MDPI AG
Date: 24-04-2020
DOI: 10.3390/NANO10040815
Abstract: An urgent demand exists for the development of novel delivery systems that efficiently transport antibacterial agents across cellular membranes for the eradication of intracellular pathogens. In this study, the clinically relevant poorly water-soluble antibiotic, rif icin, was confined within mesoporous silica nanoparticles (MSN) to investigate their ability to serve as an efficacious nanocarrier system against small colony variants of Staphylococcus aureus (SCV S. aureus) hosted within Caco-2 cells. The surface chemistry and particle size of MSN were varied through modifications during synthesis, where 40 nm particles with high silanol group densities promoted enhanced cellular uptake. Extensive biophysical analysis was performed, using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy, to elucidate the mechanism of MSN adsorption onto semi-native supported lipid bilayers (snSLB) and, thus, uncover potential cellular uptake mechanisms of MSN into Caco-2 cells. Such studies revealed that MSN with reduced silanol group densities were prone to greater particle aggregation on snSLB, which was expected to restrict endocytosis. MSN adsorption and uptake into Caco-2 cells correlated well with antibacterial efficacy against SCV S. aureus, with 40 nm hydrophilic particles triggering a ~2.5-log greater reduction in colony forming units, compared to the pure rif icin. Thus, this study provides evidence for the potential to design silica nanocarrier systems with controlled surface chemistries that can be used to re-sensitise intracellular bacteria to antibiotics by delivering them to the site of infection.
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA16028J
Abstract: Combining 1 H NMR and sSAXS to discriminate the speciation and structure evolution of lipolysis products for submicron lipid droplets and lipid loaded in porous silica particles.
Publisher: MDPI AG
Date: 06-11-2019
DOI: 10.3390/PHARMACEUTICS11110581
Abstract: Delta inulin, also known as microparticulate inulin (MPI), was modified by covalently attaching doxorubicin to its nanostructured surface for use as a targeted drug delivery vehicle. MPI is readily endocytosed by monocytes, macrophages, and dendritic cells and in this study, we sought to utilize this property to develop a system to target anti-cancer drugs to lymphoid organs. We investigated, therefore, whether MPI could be used as a vehicle to deliver doxorubicin selectively, thereby reducing the toxicity of this antibiotic anthracycline drug. Doxorubicin was covalently attached to the surface of MPI using an acid–labile linkage to enable pH-controlled release. The MPI-doxorubicin conjugate was characterized using FTIR and SEM, confirming covalent attachment and indicating doxorubicin coupling had no obvious impact on the physical nanostructure, integrity, and cellular uptake of the MPI particles. To simulate the stability of the MPI-doxorubicin in vivo, it was stored in artificial lysosomal fluid (ALF, pH 4.5). Although the MPI-doxorubicin particles were still visible after 165 days in ALF, 53% of glycosidic bonds in the inulin particles were hydrolyzed within 12 days in ALF, reflected by the release of free glucose into solution. By contrast, the fructosidic bonds were much more stable. Drug release studies of the MPI-doxorubicin in vitro, demonstrated a successful pH-dependent controlled release effect. Confocal laser scanning microscopy studies and flow cytometric analysis confirmed that when incubated with live cells, MPI-doxorubicin was efficiently internalized by immune cells. An assay of cell metabolic activity demonstrated that the MPI carrier alone had no toxic effects on RAW 264.7 murine monocyte/macrophage-like cells, but exhibited anti-cancer effects against HCT116 human colon cancer cells. MPI-doxorubicin had a greater anti-cancer cell effect than free doxorubicin, particularly when at lower concentrations, suggesting a drug-sparing effect. This study establishes that MPI can be successfully modified with doxorubicin for chemotherapeutic drug delivery.
Publisher: Equinox Publishing
Date: 22-11-2017
DOI: 10.1558/JASR.33846
Publisher: Wiley
Date: 17-11-2017
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.IJPHARM.2021.121382
Abstract: Cromoglycate is a mast cell stabiliser typically administered via inhalation or intranasally for the treatment of allergy-based respiratory issues. Oral dosing of cromoglycate remains challenging due to its high solubility but low permeability across epithelial membranes in the gastrointestinal tract: effective formulation strategies are clearly needed. Here, we investigate and preclinically develop chitosan-cromoglycate complexes and associated nano/microparticle formulations with muco-adhesive and permeation enhancing capabilities to overcome the biopharmaceutical challenges for oral dosing.The synthesized complexes were optimized with respect to chitosan grade, particle size, and drug loading and demonstrated up to a 9.3-fold enhancement in permeability across a Caco-2 monolayer for chitosan-cromoglycate particles, compared to the pure drug. This increased intestinal permeability led to improved pharmacokinetic performance of cromoglycate, e.g. up to 1.82-fold increase in relative oral bioavailability when dosed to Sprague-Dawley rats in a fasted state. These findings confirm the potential for chitosan particles to serve as an effective oral delivery vehicle for cromoglycate, with additional formulation optimization presenting the opportunity to reduce dosing frequency for treatment of allergy-based respiratory ailments.
Publisher: BRILL
Date: 28-03-2012
Publisher: Informa UK Limited
Date: 07-07-2023
Publisher: SAGE Publications
Date: 06-07-2011
Abstract: Census data from 2006 identified 133,800 Australians as being of ‘inadequately described religion’. This aggregated category conceals the exponential growth of innovative late-modern religious faiths. For ex le, leaked 2001 Census data suggests that some 71,000 Australians identified Jediism, as appropriated from the Star Wars films, as their faith. For most respondents to the Census this was no doubt an ironic late-modern play with the Census process as a response to an internet-based meme. However, evidence does suggest that a significant minority of respondents take the religion seriously. Such innovative faiths have raised the ire of some traditional religious practitioners who have responded with expressions of fear and anxiety. From a sociological perspective, this article examines the growth in innovative faiths and the backlash against them, and reports the results of a survey of university staff and students on the topic.
Publisher: Informa UK Limited
Date: 02-07-2020
Publisher: Springer International Publishing
Date: 14-10-2014
Publisher: Springer International Publishing
Date: 14-10-2014
Publisher: SAGE Publications
Date: 02-06-2015
Abstract: This article discusses the sociological understanding of popular religion by first exploring the theories of Gramsci. It then critiques this approach by arguing that the social construction of popular religion in contrast to institutionalized religion is not as clear cut in our late modern, multi-faith and global world as it was in the early modern period. Indeed, through consumer culture, some institutionalized religions are now reaching for the popular. Through the use of new Internet methodologies (e.g. Ngram Viewer), the article explores the various understandings of the words popular religion, mysticism and spirituality. It discovers that the usage of these words has evolved over time and reflects wider socio-cultural changes. The article then argues that spirituality (technical or unchurched) can be sociologically understood as an outcome of two processes that intertwine within late modernity that is the gentrification of popular religion and the democratization of mysticism.
Publisher: Springer Science and Business Media LLC
Date: 11-01-2023
DOI: 10.1007/S13346-022-01287-3
Abstract: Intracellular bacteria serve as a problematic source of infection due to their ability to evade biological immune responses and the inability for conventional antibiotics to efficiently penetrate cellular membranes. Subsequently, new treatment approaches are urgently required to effectively eradicate intracellular pathogens residing within immune cells (e.g. macrophages). In this study, the poorly soluble and poorly permeable antibiotic, rif icin, was re-purposed via micro-encapsulation within inulin-lipid hybrid (ILH) particles for the treatment of macrophages infected with small colony variants of Staphylococcus aureus (SCV S. aureus ). Rif icin-encapsulated ILH (Rif-ILH) microparticles were synthesized by spray drying a lipid nano-emulsion, with inulin dissolved throughout the aqueous phase and rif icin pre-loaded within the lipid phase. Rif-ILH were strategically designed and engineered with pH-responsive properties to promote lysosomal drug release upon cellular internalization, while preventing premature rif icin release in plasma-simulating media. The pH-responsiveness of Rif-ILH was controlled by the acid-mediated hydrolysis of the inulin coating, where exposure to acidic media simulating the lysosomal environment of macrophages triggered hydrolysis of the oligofructose chain and the subsequent diffusion of rif icin from Rif-ILH. This pH-provoked release mechanism, as well as the ability for ILH microparticles to be more readily internalized by macrophages, was found to be influential in triggering a 2.9-fold increase in intracellular rif icin concentration within infected macrophages, compared to the pure drug. The subsequent increase in exposure of intracellular pathogens to rif icin leads to a ~ 2-log improvement in antibacterial activity for Rif-ILH, at a rif icin dose of 2.5 µg/mL. Thus, the reduction in viability of intracellular SCV S. aureus , in the absence of cellular toxicity, is indicative of ILH microparticles serving as a unique approach for the safe and efficacious delivery of antibiotics to phagocytic cells for the treatment of intracellular infections. Graphical Abstract
Publisher: International Association of Physical Chemists (IAPC)
Date: 17-07-2020
DOI: 10.5599/ADMET.830
Abstract: class="ADMETabstracttext" Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.
Publisher: American Chemical Society (ACS)
Date: 28-07-2015
Abstract: Biodegradable and bioactive hybrid particles composed of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and medium-chain triglycerides were prepared by spray drying lipid-in-water emulsions stabilized by PLGA nanoparticles, to form PLGA-lipid hybrid (PLH) microparticles approximately 5 μm in mean diameter. The nanoparticle stabilizer was varied and mannitol was also incorporated during the preparation to investigate the effect of stabilizer charge and cryoprotectant content on the particle microstructure. An in vitro lipolysis model was used to demonstrate the particles' bioactivity by manipulating the digestion kinetics of encapsulated lipid by pancreatic lipase in simulated gastrointestinal fluid. Lipid digestion kinetics were enhanced in PLH and PLGA-lipid-mannitol hybrid (PLMH) microparticles for both stabilizers, compared to a coarse emulsion, in biorelevant media. An optimal digestion rate was observed for the negatively charged PLMH system, evidenced by a 2-fold increase in the pseudo-first-order rate constant compared to a coarse emulsion. Improved microparticle redispersion, probed by dual dye confocal fluorescence microscopy, increased the available surface area of lipid for lipase adsorption, enhancing digestion kinetics. Thereby, lipase action was controlled in hybrid microparticles by altering the surface charge and carbohydrate content. Our results demonstrate that bioactive microparticles composed of versatile and biodegradable polymeric particles and oil droplets have great potential for use in smart food and nutrient delivery, as well as safer and more efficacious oral delivery of drugs and drug combinations.
Publisher: American Chemical Society (ACS)
Date: 05-11-2020
Abstract: Porous colloids have been shown to exert unique bioactivities for mediating lipid (fat) metabolism and thereby offer significant potential as anti-obesity therapies. In this study, we compare the capacity for two classes of colloids, that is, smectite clays (Laponite XLG, LAP montmorillonite, MMT) and mesoporous silica (SBA-15 ordered silica MPS), to impede intestinal lipid hydrolysis and provoke lipid and carbohydrate excretion through adsorption within their particle matrices. A two-stage
Publisher: American Chemical Society (ACS)
Date: 27-07-2020
Publisher: Palgrave Macmillan US
Date: 2017
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Chemical Society (ACS)
Date: 04-03-2014
DOI: 10.1021/LA500094B
Abstract: The rate and extent of lipolysis, the breakdown of fat into molecules that can be absorbed into the bloodstream, depend on the interfacial composition and structure of lipid (fat) particles. A novel method for controlling the interfacial properties is to load the lipid into porous colloidal particles. We report on the role of pore nanostructure and surface coverage in controlling the digestion kinetics of medium-chain and long-chain triglycerides loaded into porous silica powders of different particle size, porosity, and hydrophobicity/hydrophilicity. An in vitro lipolysis model was used to measure digestion kinetics of lipid by pancreatic lipase, a digestive enzyme. The rate and extent of lipid digestion were significantly enhanced when a partial monolayer of lipid was loaded in porous hydrophilic silica particles compared to a submicrometer lipid-in-water emulsion or a coarse emulsion. The inhibitory effect of digestion products was clearly evident for digestion from a submicrometer emulsion and coarse emulsion. This effect was minimal, however, in the two silica-lipid systems. Lipase action was inhibited for lipid loaded in the hydrophobic silica and considered due to the orientation of lipase adsorption on the methylated silica surface. Thus, hydrophilic silica promotes enhanced digestion kinetics, whereas hydrophobic silica exerts an inhibitory effect on hydrolysis. Evaluation of digestion kinetics enabled the mechanism for enhanced rate of lipolysis in silica-lipid systems to be derived and detailed. These investigations provide valuable insights for the optimization of smart food microparticles and lipid-based drug delivery systems based on lipid excipients and porous nanoparticles.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JPHOTOBIOL.2022.112474
Abstract: Antimicrobial photodynamic therapy (aPDT) has emerged as an innovative strategy to combat antibiotic resistant microbes yet aPDT efficacies against biofilms are sub-optimal due to inability of photosenstizers to reach microbes embedded in biofilm matrix. To overcome this challenge, liquid crystal lipid nanoparticles (LCNP) were employed in this study as a smart, biocompatible and triggerable delivery system for the new photosensitizer gallium protoporphyrin (GaPP), due to their capabilities in promoting efficient antimicrobial delivery to biofilms. The relationship between GaPP loading of LCNP, reactive oxygen species (ROS) production and the in vitro antibacterial activity against two antibiotic resistant Staphylococcus aureus strains was established. LCNP substantially improved the antibacterial activity of GaPP, completely eradicating S. aureus and MRSA planktonic cultures, using a GaPP concentration of 0.8 μM and light dose 1.9 J/cm
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.CIS.2016.10.003
Abstract: This review describes the development of novel lipid-based biomaterials that modulate fat digestion for the enhanced uptake of encapsulated lipophilic bioactive compounds (e.g. drugs and vitamins). Specific focus is directed towards analysing how key material characteristics affect the biological function of digestive lipases and manipulate lipolytic digestion. The mechanism of lipase action is a complex, interfacial process, whereby hydrolysis can be controlled by the ability for lipase to access and adsorb to the lipid-in-water interface. However, significant conjecture exists within the literature regarding parameters that influence the activities of digestive lipases. Important findings from recent investigations that strategically examined the interplay between the interfacial composition of the lipid microenvironment and lipolysis kinetics in simulated biophysical environments are presented. The correlation between lipolysis and the rate of solubilisation and absorption of lipophilic compounds in the gastrointestinal tract (GIT) is detailed. Greater insights into the mechanism of lipase action have provided a new approach for designing colloidal carriers that orally deliver poorly soluble compounds, directly impacting the pharmaceutical and food industries.
Publisher: Equinox Publishing
Date: 03-11-2014
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.EJPS.2019.05.001
Abstract: Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.
Publisher: American Chemical Society (ACS)
Date: 21-11-2016
Abstract: Biocompatible lipid hybrid particles composed of montmorillonite and medium chain triglycerides were engineered for the first time by spray drying oil-in-water emulsions stabilized by montmorillonite platelets to form montmorillonite-lipid hybrid (MLH) microparticles containing up to 75% w/w lipid. In vitro lipolysis studies under simulated intestinal conditions indicated that the specific porous nanoarchitecture and surface chemistry of MLH particles significantly increased the rate (>10-fold) and extent of lipase-mediated digestion compared to that of coarse and homogenized submicrometer triglyceride emulsions. Proton nuclear magnetic resonance studies verified the rapid and enhanced production of fatty acids for MLH particles these are electrostatically repelled by the negatively charged montmorillonite platelet faces and avoid the "interfacial poisoning" caused by incomplete digestion that retards lipid droplet digestion. MLH particles are a novel biomaterial and encapsulation system that optimize lipase enzyme efficiency and have excellent potential as a smart delivery system for lipophilic biomolecules owing to their exceptional physicochemical and biologically active properties. These particles can be readily fabricated with varying lipid loads and thus may be tailored to optimize the solubilization of specific bioactive molecules requiring reformulation.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ADDR.2018.11.006
Abstract: Self-emulsifying drug delivery systems (SEDDS) offer potential for overcoming the inherent slow dissolution and poor oral absorption of hydrophobic drugs by retaining them in a solubilised state during gastrointestinal transit. However, the promising biopharmaceutical benefits of liquid lipid formulations has not translated into widespread commercial success, due to their susceptibility to long term storage and in vivo precipitation issues. One strategy that has emerged to overcome such limitations, is to combine the solubilisation and dissolution enhancing properties of lipids with the stabilising effects of solid carrier materials. The development of intelligent hybrid drug formulations has presented new opportunities to harness the potential of emulsified lipids in optimising oral bioavailability for lipophilic therapeutics. Specific emphasis of this review is placed on the impact of solidification approaches and excipients on the biopharmaceutical performance of self-emulsifying lipids, with findings highlighting the key design considerations that should be implemented when developing hybrid lipid-based formulations.
Publisher: BRILL
Date: 2015
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JCIS.2018.08.015
Abstract: Solid-state lipid formulations, whereby liquid lipids are encapsulated in inorganic particle matrices, have attracted significant interest for drug/nutrient delivery in recent years. We hypothesized that the surface chemistry of the inorganic material used to encapsulate lipids impacts the lipase-mediated digestion and partitioning of lipolytic species between the solubilized aqueous and insoluble pellet phases. Medium chain triglycerides were spray dried with silica nanoparticles, montmorillonite or laponite platelets to form inorganic-lipid hybrid particles. In vitro lipolysis studies were conducted under gastric (pH 1.6) and intestinal (pH 7.5) conditions, and the speciation and partitioning of lipolytic products between the aqueous and pellet phases was characterized using solution-state proton nuclear magnetic resonance and fourier transform infrared spectroscopy. Under gastric conditions, greater than 80% of all lipid species remained adsorbed within each lipolysis pellet after 60 min. Approximately 40%, 50-60% and 80-90% of all lipid species were adsorbed from solution by silica-, montmorillonite- and laponite-based particle matrices during intestinal lipolysis. Monoglycerides were preferentially adsorbed by silica, whereas triglycerides and fatty acids were adsorbed by montmorillonite and laponite. Adsorption of lipolytic products from solution is expected to impact significantly on drug/nutrient solubilization and absorption in vivo. To the best of our knowledge, this is the first report characterizing the speciation and phase behavior of lipolytic products released from solid-state lipid formulations during in vitro lipolysis studies.
Publisher: Elsevier
Date: 2021
Publisher: MDPI AG
Date: 14-01-2023
DOI: 10.3390/PHARMACEUTICS15010284
Abstract: Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations achieves higher drug loading and potentially improves solubilisation and bioavailability. However, for the weak base blonanserin, silica solidified supersaturated lipid-based formulations have demonstrated reduced in vitro solubilisation compared to their liquid-state counterparts. Therefore, this study aimed to understand the influence of supersaturated drug load on blonanserin solubilisation from liquid and silica solidified supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis. Stable liquid super-SNEDDS with varying drug loads (90–300% of the equilibrium solubility) were solidified by imbibition into porous silica microparticles (1:1 lipid: silica ratio). In vitro lipolysis revealed greater blonanserin solubilisation from liquid super-SNEDDS compared to solid at equivalent drug saturation levels, owing to strong silica-BLON/lipid interactions, evidenced by a significant decrease in blonanserin solubilisation upon addition of silica to a digesting liquid super-SNEDDS. An increase in solid super-SNEDDS drug loading led to increased solubilisation, owing to the increased drug:silica and drug:lipid ratios. Solidifying SNEDDS with silica enables the fabrication of powdered formulations with higher blonanserin loading and greater stability than liquid super-SNEDDS, however at the expense of drug solubilisation. These competing parameters need careful consideration in designing optimal super-SNEDDS for pre-clinical and clinical application.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2015
Publisher: MDPI AG
Date: 06-10-2022
DOI: 10.3390/PHARMACEUTICS14102124
Abstract: The looming antimicrobial resistance pandemic has encouraged the investigation of antimicrobial photodynamic therapy (aPDT) as a promising technology to combat recalcitrant bacterial infections caused by antibiotic resistant strains. Here, we report on the optimization and effective application of gallium protoporphyrin liquid crystalline lipid nanoparticles (GaPP-LCNP) as a photosensitizer for aPDT against the Gram-negative bacteria P. aeruginosa in both planktonic and biofilm modes of growth. LCNP significantly enhanced the performance of GaPP as photosensitizer by two-fold, which was correlated with higher antibacterial activity, reducing the viability of planktonic P. aeruginosa by 7 log10 using 0.8 µM GaPP-LCNP and a light dose of 17 J.cm−2. Importantly, GaPP-LCNP also reduced the viability of biofilms by 6 log10 at relatively low light dose of 34.2 J.cm−2 using only 3 µM GaPP-LCNP. The high antibiofilm activity of GaPP-LCNP at low GaPP-LCNP dose indicated the high efficiency and safety profile of GaPP-LCNP as a promising platform for photodynamic inactivation of recalcitrant infections.
Publisher: BRILL
Date: 2012
Publisher: American Chemical Society (ACS)
Date: 17-08-2021
Publisher: Springer International Publishing
Date: 14-10-2014
Publisher: SAGE Publications
Date: 13-04-2018
Abstract: This article focuses on the marginal extremities – the limits – of Shari’a practices in Australia, through the ex le of a criminal case in which four Sydney-based Muslim men whipped a Muslim convert to punish him for his excessive consumption of drugs and alcohol. The men claimed they acted in line with the doctrines of Shari’a practice to ‘purify’ or absolve the victim of his sins. While the case was tried before a magistrate in a lower court, it is argued in this article that its social and political significance was wider, reaching into contemporary debates around multiculturalism and immigration from non-western, non-liberal and mainly Muslim nations. Mainstream media and political narratives viewed the whipping as an ex le of the moral dangers of accommodating Shari’a norms, eliding the differences between peaceable Shari’a and its violent extremities, while situating the case at the limits of multicultural accommodation. This article interrogates the objectionable margins of some cultural practices through this limit case. At the same time it questions the limits or limitations of a multiculturalism that homogeneously views the practices of entire ethnic or religious groups as violent and incommensurable with dominant norms, while using these understandings as a justification for marginalising these groups.
Publisher: Informa UK Limited
Date: 09-2011
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.ADDR.2021.113948
Abstract: Bacteria have developed a wealth of strategies to avoid and resist the action of antibiotics, one of which involves pathogens invading and forming reservoirs within host cells. Due to the poor cell membrane permeability, stability and retention of conventional antibiotics, this renders current treatments largely ineffective, since achieving a therapeutically relevant antibiotic concentration at the site of intracellular infection is not possible. To overcome such challenges, current antibiotics are 'repurposed' via reformulation using micro- or nano-carrier systems that effectively encapsulate and deliver therapeutics across cellular membranes of infected cells. Bioinspired materials that imitate the uptake of biological particulates and release antibiotics in response to natural stimuli are recently explored to improve the targeting and specificity of this 'nanoantibiotic' approach. In this review, the mechanisms of internalization and survival of intracellular bacteria are elucidated, effectively accentuating the current treatment challenges for intracellular infections and the implications for repurposing conventional antibiotics. Key case studies of nanoantibiotics that have drawn inspiration from natural biological particles and cellular uptake pathways to effectively eradicate intracellular pathogens are detailed, clearly highlighting the rational for harnessing bioinspired drug delivery strategies.
Publisher: MDPI AG
Date: 21-07-2020
DOI: 10.3390/PHARMACEUTICS12070687
Abstract: The unique nanostructured matrix obtained by silica-lipid hybrids (SLHs) is well known to improve the dissolution, absorption, and bioavailability of poorly water-soluble drugs (PWSDs). The aim of this study was to investigate the impact of: (i) drug load: 3–22.7% w/w, (ii) lipid type: medium-chain triglyceride (Captex 300) and mono and diester of caprylic acid (Capmul PG8), and (iii) silica nanostructure: spray dried fumed silica (FS) and mesoporous silica (MPS), on the in vitro dissolution, solubilization, and solid-state stability of the model drug fenofibrate (FEN). Greater FEN crystallinity was detected at higher drug loads and within the MPS formulations. Furthermore, an increased rate and extent of dissolution was achieved by FS formulations when compared to crystalline FEN (5–10-fold), a commercial product APO-fenofibrate (2.4–4-fold) and corresponding MPS formulations (2–4-fold). Precipitation of FEN during in vitro lipolysis restricted data interpretation, however a synergistic effect between MPS and Captex 300 in enhancing FEN aqueous solubilization was attained. It was concluded that a balance between in vitro performance and drug loading is key, and the optimum drug load was determined to be between 7–16% w/w, which corresponds to (200–400% equilibrium solubility in lipid Seq). This study provides valuable insight into the impact of key characteristics of SLHs, in constructing optimized solid-state lipid-based formulations for the oral delivery of PWSDs.
Publisher: SAGE Publications
Date: 12-2017
Abstract: ‘Post-secularism’ is a term that has emerged in various disciplines, including sociology, to reflect religion’s move back into the public sphere and the need to take into account the voice of religious actors in any contemporary analysis of society. This article argues that post-secularism is, in fact, a specific type of secularism that deals with the neoliberal management of religion in the public sphere. To unpack this argument, the article will first explore what is meant by post-secularism, and then, via a case study of Shari’a in Australia, it will move to the theory of multiple modernities in order to underline the relativeness of such a term. It will then be proposed that what is meant by post-secularism is, in fact, a type of secularism (perhaps ‘late’ rather than ‘post’) in neoliberal societies.
Publisher: Elsevier BV
Date: 2021
Publisher: Informa UK Limited
Date: 02-01-2017
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.COLSURFB.2016.02.059
Abstract: Bio-active materials consisting of lipase encapsulated within porous silica particles were engineered to control the adsorption kinetics and molecular orientation of lipase, which play critical roles in the digestion kinetics of triglycerides. The adsorption kinetics of Candida antartica lipase A (CalA) was monitored using quartz crystal microbalance with dissipation (QCM-D) and controlled by altering the hydrophobicity of a silica binding support. The extent of adsorption was 2-fold greater when CalA was adsorbed onto hydrophobic silica compared to hydrophilic silica. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) fragmentation patterns, in conjunction with multivariate statistics, demonstrated enhanced exposure of the lipase's catalytic domain, specifically the histidine group responsible for activity, when CalA was adsorbed on hydrophilic silica. Consequently, lipid digestion kinetics were enhanced when CalA was loaded in hydrophilic porous silica particles, i.e., a 2-fold increase in the pseudo-first-order rate constant for digestion when compared to free lipase. In contrast, digestion kinetics were inhibited when CalA was hosted in hydrophobic porous silica, i.e., a 5-fold decrease in pseudo-first-order rate constant for digestion when compared to free lipase. These findings provide valuable insights into the mechanism of lipase action which can be exploited to develop smarter food and drug delivery systems consisting of porous lipid-based materials.
Publisher: Springer Science and Business Media LLC
Date: 15-12-2023
Publisher: American Chemical Society (ACS)
Date: 03-06-2020
Abstract: Strategies to improve the uptake of particulate delivery systems to macrophages are required for the advancement of therapeutic solutions to a range of disease states, including human immunodeficiency virus (HIV), tuberculosis, and cystic fibrosis. In this study, poly(lactic-
Publisher: SAGE Publications
Date: 22-09-2016
Abstract: Discussing the social construction of the phenomenon of exorcism, this article illustrates how it is located in contemporary culture and specifically in the religious field. Following the study done by Michel de Certeau on the mass possession of the Ursulines’ convent of Loudun (France) in the 17th century, the authors differentiate between the ‘possessed’ and the ‘possessionists’, that is between those who are possessed by the devil and those who are convinced of the reality of possession. Although the authors cannot claim that there has been a growth of possessed people, they make the claim that there has been an increase of ‘possessionists’ through the over-policing of the devil: the more the over-policing of the devil is practiced, the more people are likely to become ‘possessionist’ and believe in the increase of the presence of the devil.
Publisher: Springer Science and Business Media LLC
Date: 11-09-2021
DOI: 10.1007/S13346-020-00853-X
Abstract: Simvastatin (SIM) is a commonly used cholesterol-lowering drug that can reduce the risk of major cardiovascular events. However, due to its poor intrinsic water solubility, the drug is poorly absorbed from the gastrointestinal tract and exhibits a low oral bioavailability of approximately 5%. The aim of this study was to fabricate and optimize SIM encapsulated silica-lipid hybrids (SLH) as a solid-state lipid-based formulation to enhance absorption and bioavailability during a human in vivo pharmacokinetic study. SLH formulations were formulated by spray drying a submicron emulsion with either Aerosil® 300 fumed silica nanoparticles (SLH-A) or Syloid® 244 amorphous micronized silica (SLH-B). A cross-over, double-blinded study design was implemented to evaluate the performance of SLH formulations compared with a commercially available formulation in 12 healthy male participants after oral administration under fasting conditions. SLH formulations enhanced the bioavailability of SIM up to 1.6-fold and more importantly the active simvastatin acid (SIMA), 3.5-fold when compared with an equivalent dose of commercial formulation. The results demonstrate that the porous nanostructure of SLH impact systemic SIM and SIMA concentrations and may serve as a novel approach to enhance the bioavailability of specifically the parent or metabolite. No significant difference was observed in exposure when SLH formulations were administered at 10 mg in comparison with 20 mg of the commercial formulation, suggesting the potential for dose reduction. The study indicated that SLH formulations were safe and well-tolerated when administered to healthy males, confirming the commercial potential of SLH to enhance the bioavailability of poorly water-soluble drugs. Graphical abstract.
Publisher: Palgrave Macmillan US
Date: 2017
Publisher: Wiley
Date: 09-2012
DOI: 10.1111/ISSJ.12021
Publisher: Informa UK Limited
Date: 28-07-2016
Publisher: American Chemical Society (ACS)
Date: 18-07-2023
Publisher: CRC Press
Date: 11-08-2021
Publisher: Informa UK Limited
Date: 11-12-2018
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.VACCINE.2017.06.045
Abstract: Insoluble, nanostructured delta inulin particles enhance the immunogenicity of co-administered protein antigens and consequently are used as a vaccine adjuvant (Advax™). To better understand their immunomodulatory properties, the in vitro hydrolysis and in vivo distribution of delta inulin particles were investigated. Delta inulin particle hydrolysis under bio-relevant acidic conditions resulted in no observable change to the bulk morphology using SEM, and HPLC results showed that only 6.1% of the inulin was hydrolysed over 21days. However, 65% of the terminal glucose groups were released, showing that acid hydrolysis relatively rapidly releases surface bound chemistries. This was used to explain in vivo biodistribution results in which delta inulin particles surface-labelled with fluorescein-5-thiosemicabizide were administered to mice using intramuscular (I.M.) or subcutaneous (S.C.) routes. Comparison analysis of the fluorescence of soluble inulin in the supernatants of homogenised tissues maintained at room temperature or heated to 100°C to solubilise particulate inulin was used to distinguish between fluorescent probe on soluble inulin and probe bound to inulin within particles. Following both I.M. and S.C. injection delta inulin exhibited a depot behaviour with local injection site residence for several weeks. Over this time, as injection site inulin reduced, there was measurable transport of intact delta inulin particles by macrophages to secondary lymphoid organs and the liver. Ultimately, the injected delta inulin became solubilised resulting in its detection in the plasma and in the urine. Thus injected delta inulin particles are initially taken up by macrophages at the site of injection, trafficked to secondary lymphoid tissue and the liver, and hydrolysed resulting in their becoming soluble and diffusing into the blood stream, from whence they are glomerularly filtered and excreted into the urine. These results provide important insights into the biodistribution of I.M. or S.C. injected delta inulin particles when used as vaccine adjuvants and their method of excretion.
Publisher: American Chemical Society (ACS)
Date: 16-11-2023
Publisher: SAGE Publications
Date: 11-07-2013
Abstract: Debates about Shari’a law and legal pluralism have come to the fore of political discourse in many western multicultural societies including Australia. The mass media, in particular newspapers, have been active in reporting on Shari’a related news items and in doing so, have made a significant contribution to shaping political debate across western nations from governmental to grassroots levels. Understanding how newspapers report on Shari’a will provide important insights into how political discourse about Islam, western Muslims and Shari’a is formed. Utilizing the ex le of newspapers in Sydney, Australia, this article draws upon methodologies used to analyse the negative portrayals of new religious movements in the press. The article aims to analyse the way that Shari’a has been reported in key newspapers in Sydney over the last five years. It explores a variety of issues influencing the reporting of Shari’a including reporting of Shari’a at the local and international levels, the ision between ‘good’ Shari’a (Islamic finance) and ‘bad’ Shari’a (family and criminal law) and differences between newspapers and media owners.
Publisher: BRILL
Date: 2012
Publisher: Anthem Press
Date: 15-12-2011
Publisher: Equinox Publishing
Date: 24-01-2020
DOI: 10.1558/JASR.39972
Publisher: MDPI AG
Date: 18-01-2022
DOI: 10.3390/PHARMACEUTICS14020221
Abstract: Liposomes are widely used as carriers for anticancer drugs due to their ability to prolong the retention of encapsulated drugs in blood plasma while directing their distribution increasingly into tumor tissue. We report on the development of stealth liposomal formulations for the common chemotherapy drug 5-fluorouracil, where pharmacokinetic studies were undertaken using a microdialysis probe to specifically quantify drug accumulation in tumor, which was contrasted to drug exposure to healthy tissue. Greater accumulation of the drug into the tumor than into healthy subcutaneous tissue was observed for neutral and cationic liposomal 5-fluorouracil polymer complexes in comparison to the conventional delivery by an injected solution. Increased drug accumulation in tumor also correlated to reduced tumor growth. This research has generated new mechanistic insight into liposomal-specific delivery to tumors with potential to improve the efficacy and reduce the toxicity of chemotherapy.
Publisher: Anthem Press
Date: 15-12-2011
Publisher: MDPI AG
Date: 30-11-2022
DOI: 10.3390/PHARMACEUTICS14122659
Abstract: High-throughput permeation models are essential in drug development for timely screening of new drug and formulation candidates. Nevertheless, many current permeability assays fail to account for the presence of the gastrointestinal mucus layer. In this study, an optimised high-throughput mucus permeation model was developed employing a highly biorelevant mucus mimic. While mucus permeation is primarily conducted in a simple mucin solution, the complex chemistry, nanostructure and rheology of mucus is more accurately modelled by a synthetic biosimilar mucus (BSM) employing additional protein, lipid and rheology-modifying polymer components. Utilising BSM, equivalent permeation of various molecular weight fluorescein isothiocyanate-dextrans were observed, compared with native porcine jejunal mucus, confirming replication of the natural mucus permeation barrier. Furthermore, utilising synthetic BSM facilitated the analysis of free protein permeation which could not be quantified in native mucus due to concurrent proteolytic degradation. Additionally, BSM could differentiate between the permeation of poly (lactic-co-glycolic) acid nanoparticles (PLGA-NP) with varying surface chemistries (cationic, anionic and PEGylated), PEG coating density and size, which could not be achieved by a 5% mucin solution. This work confirms the importance of utilising highly biorelevant mucus mimics in permeation studies, and further development will provide an optimal method for high-throughput mucus permeation analysis.
Publisher: Anthem Press
Date: 15-12-2011
Publisher: Springer Science and Business Media LLC
Date: 28-08-2013
Publisher: Springer International Publishing
Date: 2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6RA08934H
Abstract: Surface immobilised lipases are important bioactive materials that have a wide range of applications in the biotechnology, chemical and pharmaceutical industries.
Publisher: SAGE Publications
Date: 02-02-2017
Abstract: This study takes the documented growth in the ministry of exorcism within the Catholic Church as a significant challenge to some accounts of secularization. After clarifying how, according to Catholic doctrine, the devil can operate in people’s lives, this study offers a sociological interpretation of exorcism. This interpretation is illustrated and tested by a sociological analysis of data collected, over a period of 10 years, by a well-established Catholic priest in Italy who himself was well trained and well grounded in philosophical analysis. This sociological case study offers fresh insights into the contemporary social significance of exorcism and provides challenges for future research. In the analysis of the data, it was discovered that only 5% of the initial consultations lead to a ritual of exorcism and that a rapprochement with rituals of deliverance is found for the large majority of the cases.
Publisher: Informa UK Limited
Date: 30-07-2020
Publisher: Informa UK Limited
Date: 18-04-2019
DOI: 10.1080/17425247.2019.1605353
Abstract: A promising approach that has recently emerged to overcome the complex biobarriers and interrelated challenges associated with oral drug absorption is to combine the benefits of polymeric and lipid-based nanocarriers within one hybrid system. This multifaceted formulation strategy has given rise to a plethora of polymer-lipid hybrid (PLH) systems with varying nanostructures and biological activities, all of which have demonstrated the ability to improve the biopharmaceutical performance of a wide range of challenging therapeutics. The multitude of polymers that can be combined with lipids to exert a synergistic effect for oral drug delivery have been identified, reviewed and critically evaluated. Specific focus is attributed to preclinical studies performed within the past 5 years that have elucidated the role and mechanism of the polymer phase in altering the oral absorption of encapsulated therapeutics. The potential of PLH systems has been clearly identified however, improved understanding of the structure-activity relationship between PLH systems and oral absorption is fundamental for translating this promising delivery approach into a clinically relevant formulation. Advancing research within this field to identify optimal polymer, lipid combinations and engineering conditions for specific therapeutics are therefore encouraged.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.XPHS.2018.09.016
Abstract: Solution proton nuclear magnetic resonance analysis was used in conjunction with in vitro lipolysis to elucidate the time-dependent speciation and release of lipolytic products during the digestion of lipid-loaded inorganic particles, allowing correlations to be made between the phase partitioning of lipolytic products and an encapsulated poorly soluble drug. Silicon dioxide, montmorillonite, and laponite were used to encapsulate medium chain triglycerides into solid-state lipid-based formulations (LBFs), and coumarin 102 was selected as a model poorly soluble compound. The specific inorganic carrier material used to encapsulate medium chain triglycerides significantly impacted the release and partitioning of the solubilizing lipolytic products, that is, diglycerides, monoglycerides, and fatty acids. A strong linear correlation was obtained between drug solubilization and fatty acid release to the aqueous phase (R
Publisher: Springer Science and Business Media LLC
Date: 28-08-2012
DOI: 10.1007/S11095-018-2552-9
Abstract: To explore the feasibility of spray dried smectite clay particles fabricated from montmorillonite or laponite materials for adsorbing dietary lipids and reducing rodent weight gain in vivo. Spray dried montmorillonite (SD-MMT) and spray dried laponite (SD-LAP) particles were prepared via spray drying. Particle morphology, surface area and redispersion/aggregation properties in aqueous media were characterized. The ability of SD-MMT and SD-LAP particles to inhibit lipid digestion kinetics and adsorb lipid species from solution was assessed during in vitro lipolysis using proton nuclear magnetic resonance analysis. SD-MMT and SD-LAP particles were dosed to rodents fed a high-fat diet and their effect on body weight gain was evaluated. Both SD-MMT and SD-LAP particles adsorbed significant quantities of medium chain triglycerides and lipolytic products from solution during in vitro lipolysis. At a concentration of 50% w/w relative to lipid content, SD-MMT and SD-LAP particles adsorbed 42% and 94% of all lipid species, respectively. SD-MMT and SD-LAP particles also reduced the extent of rodent weight gain relative to the negative control treatment group and performed similarly to orlistat via an alternate mechanism of action. Spray dried smectite clay particles (SD-MMT and SD-LAP) with significant adsorptive capacities for dietary lipids and digestion products were successfully fabricated. These particles may be developed as novel anti-obesity treatments with fewer adverse effects than currently marketed treatment options.
Publisher: American Chemical Society (ACS)
Date: 03-03-2022
DOI: 10.1021/ACS.MOLPHARMACEUT.1C00781
Abstract: SBA-15 mesoporous silica (MPS) has been widely used in oral drug delivery however, it has not been utilized for solidifying lipid-based formulations, and the impact of their characteristic intrawall microporosity remains largely unexplored. Here, we derive the impact of the MPS microporosity on the
Publisher: Oxford University Press
Date: 26-04-2019
DOI: 10.1093/ACREFORE/9780199340378.013.217
Abstract: Various social and cultural changes from modernity to late modernity have been key to the appearance and development of new spiritualities in Western society. The often-contested term of “new spiritualities” is often liked with other no less contested ones such as “mysticism,” “popular religion,” “the New Age,” and “new religious” movements. Further, if the expression new spiritualities or alternative spiritualities took off outside of institutionalized religions in the Western world, this term is now re-used by these institutions within their specific theology. As new spiritualities are becoming mainstream in the first quarter of the 21st century, they are having a low-key impact on post-secularism (i.e., a specific type of secularism characteristic of late modern societies).
Publisher: Anthem Press
Date: 15-12-2011
Publisher: Elsevier
Date: 2020
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer International Publishing
Date: 2015
Publisher: MDPI AG
Date: 04-07-2023
DOI: 10.3390/PHARMACEUTICS15071886
Abstract: Paclitaxel (PTX) and 5-fluorouracil (5-FU) are clinically relevant chemotherapeutics, but both suffer a range of biopharmaceutical challenges (e.g., either low solubility or permeability and limited controlled release from nanocarriers), which reduces their effectiveness in new medicines. Anticancer drugs have several major limitations, which include non-specificity, wide biological distribution, a short half-life, and systemic toxicity. Here, we investigate the potential of liposome-micelle-hybrid (LMH) carriers (i.e., drug-loaded micelles encapsulated within drug-loaded liposomes) to enhance the co-formulation and delivery of PTX and 5-FU, facilitating new delivery opportunities with enhanced chemotherapeutic performance. We focus on the combination of liposomes and micelles for co-delivery of PTX and 5_FU to investigate increased drug loading, improved solubility, and transport ermeability to enhance chemotherapeutic potential. Furthermore, combination chemotherapy (i.e., containing two or more drugs in a single formulation) may offer improved pharmacological performance. Compared with in idual liposome and micelle formulations, the optimized PTX-5FU-LMH carriers demonstrated increased drug loading and solubility, temperature-sensitive release, enhanced permeability in a Caco-2 cell monolayer model, and cancer cell eradication. LMH has significant potential for cancer drug delivery and as a next-generation chemotherapeutic.
Publisher: BRILL
Date: 2012
Publisher: Springer Singapore
Date: 2018
Publisher: American Chemical Society (ACS)
Date: 11-09-2015
DOI: 10.1021/ACS.LANGMUIR.5B02476
Abstract: Quartz crystal microbalance with dissipation (QCM-D) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to provide insights into the relationship between lipid adsorption kinetics and molecular behavior in porous silica particles of varying hydrophobicities on lipase activity. Lipase (an interfacial enzyme that cleaves ester bonds to break down lipids to fatty acids and monoglycerides) activity was controlled by loading triglycerides at different surface coverages in hydrophilic and hydrophobic porous silica particles. The rate of lipid adsorption increased 2-fold for the hydrophobic surface compared to the hydrophilic surface. However, for submonolayer lipid coverage, the hydrophilic surface enhanced lipase activity 4-fold, whereas the hydrophobic surface inhibited lipase activity 16-fold, compared to lipid droplets in water. A difference in lipid orientation for low surface coverage, evidenced by ToF-SIMS, indicated that lipid adsorbs to hydrophilic silica in a conformation promoting hydrolysis. Multilayer coverage on hydrophobic and hydrophilic surfaces was indistinguishable with ToF-SIMS analysis. Increased lipid adsorption for both substrates facilitated digestion kinetics comparable to a conventional emulsion. Improved understanding of the interfacial adsorption and orientation of lipid and its digestibility in porous silica has implications in improving the uptake of pharmaceuticals and nutrients from lipid-based delivery systems.
Publisher: Philosophy Documentation Center
Date: 2011
DOI: 10.5840/ASRR2011227
Publisher: Informa UK Limited
Date: 30-06-2016
Publisher: Informa UK Limited
Date: 30-06-2016
Publisher: American Chemical Society (ACS)
Date: 04-02-2020
Publisher: American Chemical Society (ACS)
Date: 04-10-2017
DOI: 10.1021/ACS.MOLPHARMACEUT.7B00676
Abstract: Three state-of-the-art drug delivery vehicles engineered by nanostructuring lipid colloids within solid particle matrices were fabricated for the oral delivery of the poorly water-soluble, weak base, cinnarizine (CIN). The lipid and solid phase of each formulation was varied to systematically analyze the impact of key material characteristics, such as nanostructure and surface chemistry, on the in vitro and in vivo fate of CIN. The three systems formulated were: silica-stabilized lipid cubosomes (SSLC), silica-solid lipid hybrid (SSLH), and polymer-lipid hybrid (PLH) particles. Significant biopharmaceutical advantages were presented for CIN when solubilized in the polymer (poly(lactic-co-glycolic) acid PLGA) and lipid phase of PLH particles compared to the lipid phases of SSLC and SSLH particles. In vitro dissolution in simulated intestinal conditions highlighted reduced precipitation of CIN when administered within PLH particles, given by a 4-5-fold improvement in the extent of CIN dissolution compared to the other delivery vehicles. Furthermore, CIN solubilization was enhanced 1.5-fold and 6-fold under simulated fasted state lipid digestion conditions when formulated with PLH particles compared to SSLH and SSLC particles, respectively. In vivo pharmacokinetics correlated well with in vitro solubilization data, whereby oral CIN bioavailability in rats, when encapsulated in the corresponding formulations, increased from SSLC < SSLH < PLH. The pharmacokinetic data obtained throughout this study indicated a synergistic effect between PLGA nanoparticles and lipid droplets in preventing CIN precipitation and thus, enhancing oral absorption. This synergy can be harnessed to efficiently deliver challenging poorly water-soluble, weak bases through oral administration.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2018
Publisher: Elsevier BV
Date: 06-2020
Publisher: Informa UK Limited
Date: 18-06-2023
Publisher: Elsevier BV
Date: 11-2023
Publisher: Springer Science and Business Media LLC
Date: 31-03-2020
Publisher: MDPI AG
Date: 17-01-2023
DOI: 10.3390/PHARMACEUTICS15020305
Abstract: Cutaneous chronic wounds impose a silent pandemic that affects the lives of millions worldwide. The delayed healing process is usually complicated by opportunistic bacteria that infect wounds. Staphylococcus aureus is one of the most prevalent bacteria in infected cutaneous wounds, with the ability to form antibiotic-resistant biofilms. Recently, we have demonstrated the potential of gallium protoporphyrin lipid liquid crystalline nanoparticles (GaPP-LCNP) as a photosensitizer against S. aureus biofilms in vitro. Herein, we investigate the potential of GaPP-LCNP using a pre-clinical model of infected cutaneous wounds. GaPP-LCNP showed superior antibacterial activity compared to unformulated GaPP, reducing biofilm bacterial viability by 5.5 log10 compared to 2.5 log10 in an ex vivo model, and reducing bacterial viability by 1 log10 in vivo, while unformulated GaPP failed to reduce bacterial burden. Furthermore, GaPP-LCNP significantly promoted wound healing through reduction in the bacterial burden and improved early collagen deposition. These findings pave the way for future pre-clinical investigation and treatment optimizations to translate GaPP-LCNP towards clinical application.
Publisher: Wiley
Date: 25-11-2020
Abstract: There is an urgent demand for analytic approaches that enable precise and representative quantification of the transport of biologically active compounds across cellular membranes. In this study, we established a new means to monitor membrane permeation kinetics, using total internal reflection fluorescence microscopy confined to a ≈500 nm thick mesoporous silica substrate, positioned underneath a planar supported cell membrane mimic. This way, we demonstrate spatiotemporally resolved membrane permeation kinetics of a small‐molecule model drug, felodipine, while simultaneously controlling the integrity of, and monitoring the drug binding to, the cell membrane mimic. By contrasting the permeation behaviour of pure felodipine with felodipine coupled to the permeability enhancer caprylate (C8), we provide evidence for C8‐facilitated transport across lipid membranes, thus validating the potential for this approach to successfully quantify carrier system‐induced changes to cellular membrane permeation.
Publisher: MDPI AG
Date: 29-08-2022
DOI: 10.3390/PHARMACEUTICS14091813
Abstract: The potential for porous silica to serve as an effective anti-obesity agent has received growing attention in recent years. However, neither the exact pharmacological mechanism nor the fundamental physicochemical properties of porous silica that drive its weight-lowering effect are well understood. Subsequently, in this study, an advanced in vitro digestion model capable of monitoring lipid and carbohydrate digestion was employed to elucidate the effect of porous silica supplementation on digestive enzyme activities. A suite of porous silica s les with contrasting physicochemical properties was investigated, where it was established that the inhibitory action of porous silica on digestive enzyme functionality was strongly dependent on porous nanostructure, particle size and morphology, and surface chemistry. Insights derived from this study validate the capacity of porous silica to impede the digestive processes mediated by pancreatic lipase and α-amylase within the gastrointestinal tract, while the subtle interplay between porous nanostructure and enzyme inhibition indicates that the anti-obesity effect can be optimized through strategic particle design.
Publisher: American Chemical Society (ACS)
Date: 11-08-2021
Location: Australia
Start Date: 02-2022
End Date: 02-2027
Amount: $4,997,903.00
Funder: Australian Research Council
View Funded Activity