ORCID Profile
0000-0002-0194-7058
Current Organisation
The Chinese University of Hong Kong
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Publisher: Springer Science and Business Media LLC
Date: 03-09-2015
DOI: 10.1007/S11095-015-1786-Z
Abstract: To investigate the applicability of Bipolar Charge Analyzer (BOLAR), a new commercial instrument developed by Dekati Ltd., in simultaneously characterizing the bipolar electrostatic charge profile and measuring the size distribution of commercial metered dose inhalers (MDIs). Intal Forte(®) (sodium cromoglycate), Tilade(®) (nedocromil sodium), Ventolin(®) (salbutamol sulphate), and QVAR(®) (beclomethasone dipropionate) were used as model MDIs in this study. Three in idual actuations of each MDI were introduced into the BOLAR at an air flow rate of 60 l/min. Charge and mass profiles for each actuation were determined. The BOLAR was found to have better performance in collecting valid charge data (≥80%) than valid mass data (≥50%). In all tested products, both positively and negatively charged particles were found in five defined size fractions between zero and 11.6 μm, with the charge magnitude decreased with increasing particle size. The net charge profiles obtained from the BOLAR qualitatively agreed with the results reported previously. In all suspension type MDIs, negligible masses were detected in the smallest size fraction (<0.95 μm), for which the charge was most likely caused by the propellant and excipients. QVAR was the only solution MDI tested and the charge and mass profiles were significantly different from the suspension-type MDIs. Its mass profile was found to follow closely with the charge profile. Positively and negatively charged MDI particles of different size fractions and their corresponding charge-to-mass profiles were successfully characterized by the BOLAR.
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.IJPHARM.2018.04.063
Abstract: Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows reproducible mixing in miliseconds on the nanoliter scale. Here we investigated the feasibility of a microfluidic flow focusing setup built from commercially available fittings to encapsulate phages into liposomes. Two types of Pseudomonas phages, PEV2 (Podovirus, ∼65 nm) and PEV40 (Myovirus, ∼220 nm), were used as model phages. A mixture of soy phosphatidylcholine and cholesterol at a ratio of 4:1 dissolved in absolute ethanol with a total solid content of 17.5 mg/mL was injected through the center inlet channel of a cross mixer. Phage suspensions were injected into the cross mixer from the two side channels intersecting with the center channel. The total flow rate (TFR) varied 160-320 µL/min and the organic/aqueous flow rate ratio (FRR) varied 1:3-2:3. The size of liposomes and the encapsulation efficiency both increased with increasing FRR and slightly decreased with increasing TFR. Due to the different size of the two studied phages, the size of liposomes encapsulating PEV2 were smaller (135-218 nm) than those encapsulating the Myovirus PEV40 (261-448 nm). Highest encapsulation efficiency of PEV2 (59%) and PEV40 (50%) was achieved at a TFR of 160 µL/ml and a FRR of 2:3. Generally, the encapsulation efficiency was slightly higher than that obtained from the conventional thin film hydration followed by extrusion method. In summary, the proposed microfluidic technique was capable of encapsulating phages of different size into liposomes with reasonable encapsulation efficiency and minimal titer reduction.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 14-03-2016
DOI: 10.1007/S11095-016-1887-3
Abstract: Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations. Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 μm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose. SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.
Publisher: Mary Ann Liebert Inc
Date: 12-2015
Abstract: Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol. The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT. Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction. A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.
Publisher: Frontiers Media SA
Date: 03-07-2020
Publisher: Springer Science and Business Media LLC
Date: 02-2023
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.IJPHARM.2017.07.033
Abstract: The aim of this study was to investigate the ability of L-leucine (LL) in preventing moisture-induced deterioration in the in vitro aerosolization performance of spray-dried (SD) salbutamol sulfate (SS). Increasing mass fraction of LL (5-80%) were co-spray dried with SS, and the physicochemical properties of the powders were characterized by laser diffraction, X-ray powder diffraction (XRD) and dynamic vapour sorption (DVS). Furthermore, the surface morphology and chemistry of fine particles was analyzed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The in vitro aerosolization performance of powders stored at different relative humidity (RH) was evaluated by a next generation impactor (NGI). The SD SS powders were moderately hygroscopic and amorphous, of which the uptake of moisture upon storage caused a drop in the aerosolization performance. The results showed that 40% (w/w) LL was sufficient to eliminate the effect of moisture on the aerosolization performance at 60% RH. The formulation containing 40% (w/w) LL also maximized the aerosolization performance of SD SS powders (stored in desiccator) with the emitted fraction being 90.0±1.8%, and the fine particle fraction based on the recovered dose (FPF
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JPHOTOBIOL.2020.111776
Abstract: Due to the emergence of antibiotic resistance, antimicrobial photodynamic therapy (aPDT) has recently been demonstrated as a promising alternative to antibiotics to treat wound infections caused by multidrug-resistant (MDR) pathogens. This study aimed to evaluate the bacterial killing efficiency of aPDT mediated by methylene blue (MB) loaded thermosensitive hydrogels against methicillin-resistant Staphylococcus aureus (MRSA). Box-Behnken Design method was employed to investigate the impacts of the polymer compositions, Poloxamer 407, Poloxamer 188 and Carbopol 934P, on the gelation temperature (T
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 02-2022
DOI: 10.1302/2046-3758.112.BJR-2021-0299.R1
Abstract: With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Staphylococcus aureus at 4 × 10 4 colony-forming units (CFU)/ml was inoculated. Rats were euthanized at four and eight weeks post-surgery. Radiography, micro-CT, haematoxylin-eosin, mechanical testing, immunohistochemistry (IHC), gram staining, agar plating, crystal violet staining, and scanning electron microscopy were performed. Agar plating analysis revealed a higher bacterial load in bone (p = 0.002), and gram staining showed higher cortical bone colonization (p = 0.039) in OVX-Inf compared to Sham-Inf. OVX-Inf showed significantly increased callus area (p = 0.013), but decreased high-density bone volume (p = 0.023) compared to Sham-Inf. IHC staining showed a significantly increased expression of TNF-α in OVX-Inf compared to OVX (p = 0.049). Significantly reduced bacterial load on bone (p = 0.001), enhanced ultimate load (p = 0.001), and energy to failure were observed in Sham-Inf-A compared to Sham-Inf (p = 0.028), but not in OVX-Inf-A compared to OVX-Inf. In osteoporotic bone with FRI, infection was more severe with more bone lysis and higher bacterial load, and fracture-healing was further delayed. Systemic antibiotics significantly reduced bacterial load and enhanced callus quality and strength in normal bone with FRI, but not in osteoporotic bone. Cite this article: Bone Joint Res 2022 (2):49–60.
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.EJPS.2019.104988
Abstract: Piperine, an alkaloid from black pepper, has demonstrated beneficial effects in central nervous system, especially in epilepsy control. However, its therapeutic application remains limited due to the low aqueous solubility of piperine. Thus, the present study aimed to formulate piperine into a more solubilized form to enhance its oral bioavailability and facilitate its development as a potential anti-epileptic treatment. The nanoprecipitation method was applied to prepare piperine nanoparticles, which were then examined under transmission electron microscopy. A spherical nanosized particle was obtained with small particle size (average particle size 130.20 ± 1.57 nm), narrow size distribution (polydispersity index 0.195 ± 0.002) and efficient entrapment (entrapment efficiency 92.2 ± 2.5%). Compared with the unformulated piperine, nanosized piperine had a much faster dissolution rate with 3 times higher accumulated drug release after 24 h. After oral administration at 3.5 mg/kg in rats, the nanosized piperine formulations could improve its oral bioavailability by 2.7-fold with 16 times higher concentrations in brain at 10 h postdosing. Moreover, the piperine nanoparticles exhibited effective protection against pentylenetetrazol-induced seizures in both zebrafish and mice. In summary, the present study provided a simple formulation strategy for oral administration of piperine to overcome its limitation in water solubility. The developed formulations could effectively enhance oral bioavailability of piperine with promising anti-epileptic effect, which could be applied as a potential therapy in epilepsy control.
Publisher: Springer Science and Business Media LLC
Date: 09-01-2017
DOI: 10.1208/S12248-016-0039-3
Abstract: This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9-27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the mannitol content and CsA loading. The initial dissolution rates of the present formulations were almost double than that of the spray-dried counterpart, with 90% of the drug dissolved in 10 min. Overall, the CsA NPs were successfully incorporated into the porous mannitol which demonstrated good aerosol performance and enhanced dissolution profiles. These spray-freeze-drying (SFD) powders were stable after 2-year storage under desiccation at 20 ± 3°C.
Publisher: MDPI AG
Date: 28-07-2021
DOI: 10.3390/PHARMACEUTICS13081162
Abstract: The feasibility of using respirable bacteriophage (phage) powder to treat lung infections has been demonstrated in animal models and clinical studies. This work investigated the influence of formulation compositions and excipient concentrations on the aerosol performance and storage stability of phage powder. An anti-Acinetobacter baumannii phage vB_AbaM-IME-AB406 was incorporated into dry powders consisting of trehalose, mannitol and L-leucine for the first time. The phage stability upon the spray-drying process, room temperature storage and powder dispersion under different humidity conditions were assessed. In general, powders prepared with higher mannitol content (40% of the total solids) showed a lower degree of particle merging and no sense of stickiness during s le handling. These formulations also provided better storage stability of phage with no further titer loss after 1 month and log titer loss in 6 months at high excipient concentration. Mannitol improved the dispersibility of phage powders, but the in vitro lung dose dropped sharply after exposure to high-humidity condition (65% RH) for formulations with 20% mannitol. While previously collected knowledge on phage powder preparation could be largely extended to formulate A. baumannii phage into inhalable dry powders, the environmental humidity may have great impacts on the stability and dispersion of phage therefore, specific attention is required when optimizing phage powder formulations for global distribution.
Publisher: Springer Science and Business Media LLC
Date: 23-07-2015
Publisher: Elsevier BV
Date: 02-2012
Publisher: Elsevier BV
Date: 02-2012
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.EJPS.2016.03.024
Abstract: Inhaled delivery of drugs incorporated into poly (lactic-co-glycolic acid) (PLGA) microparticles allows a sustained lung concentration and encourages phagocytosis by alveolar macrophages that harboring Mycobacterium tuberculosis. However, limited data are available on the effects of physicochemical properties of PLGA, including the monomer ratio (lactide:glycide) and molecular weight (MW) on the aerosol performance, macrophage uptake, and toxicity profile. The present study aims to address this knowledge gap, using PLGAs with monomer ratios of 50:50, 75:25 and 85:15, MW ranged 24 - 240kDa and an anti-tuberculosis (TB) drug, rifapentine. The PLGA-rifapentine powders were produced through a solution spray drying technique. The particles were spherical with a smooth surface and a volume median diameter around 2μm (span ~2). When the powders were dispersed using an Osmohaler(®) at 100L/min for 2.4s, the fine particle fraction (FPFtotal, wt.% particles in aerosol <5μm relative to the total recovered drug mass) was ranged between 52 and 57%, with no significant difference between the formulations. This result suggests that the monomer ratio and MW are not crucial parameters for the aerosol performance of PLGA. The phagocytosis analysis was performed using Thp-1 monocyte-derived macrophages. The highest rate of uptake was observed in PLGA 85:15 followed by 75:25 and 50:50 with about 90%, 80% and 70%, respectively phagocytosis over 4h of exposure. Furthermore, the cytotoxicity analysis on Thp-1 and human lung adenocarcinoma epithelial cells demonstrated that PLGA concentration up to 1.5mg/mL, regardless of the monomer composition and MW, were non-toxic. In conclusion, the monomer ratio and MW are not crucial in determining the aerosol performance and cytotoxicity profile of PLGA however, the particles with high lactide composition have a superior tendency for macrophage uptake.
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
Publisher: Springer Science and Business Media LLC
Date: 24-04-2019
DOI: 10.1208/S12248-019-0326-X
Abstract: Challenges of ophthalmic drug delivery arise from not only the limited solubility of hydrophobic therapeutics, but also the restricted permeability and fast clearance of drugs due to the complex anatomy and physiology of the eyes. Biodegradable thermosensitive polymer, poly(dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) is a desirable ophthalmic drug delivery system because it can be formulated into injectable solution which forms gel in situ to provide prolonged drug release. In this study, excellent biocompatibility of blank PLGA-PEG-PLGA (1800-1500-1800) thermogel was demonstrated with insignificant difference from saline noted in rat eye enucleation test, in vivo inflammation test upon topical instillation, and subconjunctival injection. After subconjunctival injection, thermogel formulations loaded with hydrophilic (rhodamine B) or hydrophobic (coumarin 6) fluorescent dyes were retained up to 4 weeks in eye tissues and significantly higher level was detected than rhodamine B solution or coumarin 6 suspension in weeks 3 and 4. Moreover, in vivo whole body imaging showed that dye-loaded (sulfo-cyanine 7 NHS ester, Cy7 or cyanine 7.5 alkyne, Cy7.5) thermogels had longer retention at the injection site and retarded release to other body parts than dye solutions. Generally, the release rate of hydrophobic dyes (coumarin 6 and Cy7.5) was much slower than that of the hydrophilic dyes (rhodamine B and Cy7) from the thermogel. In summary, the thermogel was safe for ophthalmic drug delivery and could deliver both hydrophobic and hydrophilic compounds for sustained drug release into eye tissues with single subconjunctival injection for better patient compliance and reduced risks on repeated injection.
Publisher: Elsevier BV
Date: 06-2012
Publisher: Springer Science and Business Media LLC
Date: 23-06-2017
DOI: 10.1007/S11095-017-2213-4
Abstract: To compare titer reduction and delivery rate of active anti-tuberculosis bacteriophage (phage) D29 with three inhalation devices. Phage D29 lysate was lified to a titer of 11.8 ± 0.3 log Respective titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log Delivering active phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing phage D29 under the tested conditions, due to substantial titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1NR00032B
Abstract: A self-assembled nanomedicine combining Ber and Dox with high drug loading was developed, which could translocate Dox from the nucleus to mitochondria and finally inhibit tumor proliferation and metastasis simultaneously via mitochondrial pathways.
Publisher: Frontiers Media SA
Date: 14-02-2020
Publisher: Elsevier BV
Date: 11-2023
Publisher: Wiley
Date: 2023
DOI: 10.1002/HPJA.692
Publisher: Future Medicine Ltd
Date: 02-2019
Abstract: In the development of cancer chemotherapy, besides the discovery of new anticancer drugs, a variety of nanocarrier systems for the delivery of previously developed and new chemotherapeutic drugs have currently been explored. Liposome is one of the most studied nanocarrier systems because of its biodegradability, simple preparation method, high efficacy and low toxicity. To make the best use of this vehicle, a number of multifunctionalized liposomal formulations have been investigated. The objective of this review is to summarize the current development of novel active targeting liposomal formulations, and to give insight into the challenges and future direction of the field. The recent studies in active targeting liposomes suggest the great potential of precise targeted anticancer drug delivery in cancer therapeutics.
Publisher: Informa UK Limited
Date: 28-03-2014
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.IJPHARM.2018.11.026
Abstract: It was previously demonstrated that the loss of infectivity of a myovirus PEV44 after jet nebulization was closely related to a change in bacteriophage (phage) structure. In this follow-up study, we further examined the impact of jet nebulization on tailed phages, which constitute 96% of all known phages, from three different families, Podoviridae (PEV2), Myoviridae (PEV40) andSiphoviridae (D29). Transmission electron microscopy (TEM) identified major changes in phage structures after jet nebulization, correlating with their loss of infectivity. For the podovirus PEV2, jet nebulization had a negligible impact on its activity (0.04 log
Publisher: Elsevier BV
Date: 11-2020
Publisher: Open Exploration Publishing
Date: 30-06-2023
Abstract: Aim: This study aims to report an engineered peptide zp39 with favorable bioactivity against enterohemorrhagic Escherichia coli (E. coli, EHEC). Its antibacterial mechanisms and application in a real food system are assessed. Methods: Spatial conformation of synthetic peptide zp39 (GIIAGIIiKIKk-NH2, lowercase letters indicate dextrorotatory amino acids) was predicted by PEPstrMOD and its secondary structure was further determined by circular dichroism (CD) spectroscopy. Then, standard E. coli O157:H7 strain ATCC 43888 was used to evaluate the bioactivity of zp39. A double dilution method was applied to investigate its efficacy in normal broth medium, serum, and highly saline conditions. Its effects on cell membrane permeability and potential were measured by fluorescent assays. Thereafter, morphological changes of E. coli O157:H7 cells were monitored by electron microscopy technologies. Finally, the potential application of zp39 in controlling EHEC in food was tested with spinach juice and the Galleria mellonella larvae model was employed to assess the in vivo efficacy. Results: Peptide zp39 presented an hiphilic helical structure. It effectively inhibited the growth of E. coli O157:H7 at a concentration of 4 μmol/L in a bactericidal mode. Mechanistic studies revealed that it affected membrane permeability and potential in a dose-dependent manner. Moreover, zp39 maintained satisfactory bioactivity against E. coli O157:H7 even in the presence of 70% serum or 1,000 μmol/L chloride salts. In spinach juice application, 90% E. coli O157:H7 cells were killed within 2 h after exposure to 64 μmol/L zp39. In vivo study proved that treatment with 64 μmol/L zp39 could effectively boost the survival ratio of infected larvae by 50%. Conclusions: This study depicts a synthetic dodecapeptide that shows the potential application in controlling EHEC. This molecule may be developed into a highly effective antimicrobial agent applied to prevent food contamination and associated infections.
Publisher: Elsevier BV
Date: 12-2010
Publisher: Springer Science and Business Media LLC
Date: 19-09-2022
Publisher: American Chemical Society (ACS)
Date: 20-07-2012
DOI: 10.1021/IE200610K
Publisher: Frontiers Media SA
Date: 18-03-2019
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.IJPHARM.2019.01.030
Abstract: Thermosensitive hydrogels are in situ gelling systems composed of hydrophilic homopolymers or block copolymers which remain as solutions at room temperature and form gels after administration into the body. Its application in advanced drug delivery has gained significant attention in recent years. The tunable characteristics of thermosensitive hydrogels make them versatile and capable of incorporating both hydrophilic and lipophilic compounds and macromolecules. The drug molecules can be included as free molecules or preformulated into nano- or micro-particles or liposomes. Although there were several reviews on the materials of thermosensitive hydrogels, the compatibility between the drug and thermosensitive material as well as its in vitro release mechanisms and in vivo performance have barely been investigated. The current review is proposed aiming to not only provide an update on the recent development in thermosensitive hydrogel formulations for nasal, ocular and cutaneous deliveries, but also identify the relationship between the drug characteristics and the loading strategies, and their impacts on the release mechanisms and the in vivo performance. Our current update for the first time highlights the essential features for successful development of in situ thermosensitive hydrogels to facilitate nasal, ocular or cutaneous drug deliveries.
Publisher: Informa UK Limited
Date: 03-09-2021
Publisher: Frontiers Media SA
Date: 30-04-2019
Publisher: Wiley
Date: 31-07-2023
DOI: 10.5694/MJA2.52055
Abstract: To describe the frequency of hospitalisation and in‐hospital death following moderate to severe traumatic brain injury (TBI) in Australia, both overall and by patient demographic characteristics and the nature and severity of the injury. Cross‐sectional study analysis of Australia New Zealand Trauma Registry data. People with moderate to severe TBI (Abbreviated Injury Score [head] greater than 2) who were admitted to or died in one of the twenty‐three major Australian trauma services that contributed data to the ATR throughout the study period, 1 July 2015 – 30 June 2020. Primary outcome: number of hospitalisations with moderate to severe TBI secondary outcome: number of deaths in hospital following moderate to severe TBI. During 2015–20, 16 350 people were hospitalised with moderate to severe TBI (mean, 3270 per year), of whom 2437 died in hospital (14.9% mean, 487 per year). The mean age at admission was 50.5 years (standard deviation [SD], 26.1 years), and 11 644 patients were male (71.2%) the mean age of people who died in hospital was 60.4 years (SD, 25.2 years), and 1686 deaths were of male patients (69.2%). The overall number of hospitalisations did not change during 2015–20 (per year: incidence rate ratio [IRR], 1.00 95% confidence interval [CI], 0.99–1.02) and death (IRR, 1.00 95% CI, 0.97–1.03). Injury prevention and trauma care interventions for people with moderate to severe TBI in Australia reduced neither the incidence of the condition nor the associated in‐hospital mortality during 2015–20. More effective care strategies are required to reduce the burden of TBI, particularly among younger men.
Publisher: Cold Spring Harbor Laboratory
Date: 27-05-2021
DOI: 10.1101/2021.05.26.445908
Abstract: Bacteriophage-encoded depolymerases are responsible for degrading capsular polysaccharides (CPS), lipopolysaccharides (LPS) and exopolysachcharides (EPS) of the host bacteria during phage invasion. They have been considered as promising antivirulence agents in controlling bacterial infections, including those caused by drug-resistant bacteria. This feature inspires a hope of utilizing these enzymes to disarm the polysaccharide capsid of the bacterial cells, which then strengthens the action of antibiotics. Here we have identified, cloned, and expressed a depolymerase Dpo71 from a bacteriophage specific for the gram-negative (G-ve) bacterium Acinetobacter baumannii in the heterologous host E. coli . Dpo71 sensitizes the multidrug-resistant (MDR) A. baumannii to the host immune attack, and also acts as an adjuvant to assist or boost the action of antibiotics, for ex le colistin. Specifically, Dpo71 at 10 µg/ml enables a complete bacterial eradication by human serum at 50% volume ratio. Dpo71 inhibits biofilm formation and disrupts the pre-formed biofilm. Combination of Dpo71 could significantly enhance the antibiofilm activity of colistin, and improve the survival rate of A. baumannii infected Galleria mellonella . Dpo71 retains the strain-specificity of the parent phage from which Dpo71 is derived: the phage-sensitive A. baumannii strains respond to Dpo71 treatment, whereas the phage-insensitive strains do not. This indicates that Dpo71 indeed is responsible for the host specificity of bacteriophages. In summary, our work demonstrates the feasibility of using recombinant depolymerases as an antibiotic adjuvants to supplement the development of new antibacterials and to battle against MDR pathogens.
Publisher: MDPI AG
Date: 02-2021
DOI: 10.3390/PHARMACEUTICS13020189
Abstract: Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.EJPB.2018.01.010
Abstract: Reduced infectivity of phage due to the nebulization process has been reported previously, but no visual evidence on structural change upon nebulization has been established, or whether these structural changes can be attributed to the titer reduction. In this study, transmission electron microscopy (TEM) was employed to assess the impact of three different types of nebulizers, air-jet, vibrating-mesh and static-mesh nebulizers, on the structural stability of a Myoviridae phage, PEV44, active against Pseudomonas aeruginosa. The morphology of the phage in the nebulized s les was categorized into two groups: "whole" (the capsid and tail held together) and "broken" (the capsid separated from the tail) phages. The "whole" phage group was further ided into three sub-groups: (1) intact, (2) contracted tail and (3) empty capsid. The starting stock suspension was found to contain considerable portions of "broken" phages (35.5 ± 6.7%), "whole" phages with contracted tails (9.9 ± 5.4%) and empty capsids (19.3 ± 8.9%). The fraction of "broken" phages was significantly increased after nebulization, with the air-jet nebulizer (83%) being more pronounced than the mesh type nebulizers (50-60%). While the amount of intact phages (2-10%) and whole phages with contracted tails (0-3%) were significantly decreased, the proportion of phages with empty capsids (15-36%) were not significantly different. Phages with broken features obtained by TEM quantification were 92.9 ± 3.2%, 74.8 ± 10.4% and 71.2 ± 11.0% for the jet, vibrating-mesh and static-mesh nebulizers, respectively. These results were found to be comparable with the titer loss obtained by the conventional plaque assay results. The in vitro aerosol performance and viable phage delivery of the three nebulizers was also assessed. The Omron nebulizer achieved a significantly higher viable respirable fraction (VRF) than the SideStream and Aeroneb Go (15.1 ± 5.8%, 2.4 ± 2.0%, 4.1 ± 2.7% respectively). In conclusion, this study identified various changes in the phage structure and viability of phage from different types of nebulizers. Understanding these effects and the phage tolerance to nebulization stresses can potentially improve our choice of the delivery method for inhaled phage therapy.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.ADDR.2014.03.006
Abstract: Novel inhaled therapeutics including antibiotics, vaccines and anti-hypertensives, have led to innovations in designing suitable delivery systems. These emerging design technologies are in urgent demand to ensure high aerosolisation performance, consistent efficacy and satisfactory patient adherence. Recent vibrating-mesh and software technologies have resulted in nebulisers that have remarkably accurate dosing and portability. Alternatively, dry powder inhalers (DPIs) have become highly favourable for delivering high-dose and single-dose drugs with the aid of advanced particle engineering. In contrast, innovations are needed to overcome the technical constrains in drug-propellant incompatibility and delivering high-dose drugs with pressurised metered dose inhalers (pMDIs). This review discusses recent and emerging trends in pulmonary drug delivery systems.
Publisher: Springer Science and Business Media LLC
Date: 09-06-2023
DOI: 10.1186/S12913-023-09567-5
Abstract: Aboriginal and Torres Strait Islander peoples have a unique place in Australia as the original inhabitants of the land. Similar to other First Nations people globally, they experience a disproportionate burden of injury and chronic health conditions. Discharge planning ensures ongoing care to avoid complications and achieve better health outcomes. Analysing discharge interventions that have been implemented and evaluated globally for First Nations people with an injury or chronic conditions can inform the implementation of strategies to ensure optimal ongoing care for Aboriginal and Torres Strait Islander people. A systematic review was conducted to analyse discharge interventions conducted globally among First Nations people who sustained an injury or suffered from a chronic condition. We included documents published in English between January 2010 and July 2022. We followed the reporting guidelines and criteria set in Preferred Reporting Items for Systematic Review (PRISMA). Two independent reviewers screened the articles and extracted data from eligible papers. A quality appraisal of the studies was conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. Four quantitative and one qualitative study out of 4504 records met inclusion criteria. Three studies used interventions involving trained health professionals coordinating follow-up appointments, linkage with community care services and patient training. One study used 48-hour post discharge telephone follow-up and the other text messages with prompts to attend check-ups. The studies that included health professional coordination of follow-up, linkage with community care and patient education resulted in decreased readmissions, emergency presentations, hospital length of stay and unattended appointments. Further research on the field is needed to inform the design and delivery of effective programs to ensure quality health aftercare for First Nations people. We observed that discharge interventions in line with the principal domains of First Nations models of care including First Nations health workforce, accessible health services, holistic care, and self-determination were associated with better health outcomes. This study was prospectively registered in PROSPERO (ID CRD42021254718).
Publisher: MDPI AG
Date: 09-06-2022
DOI: 10.3390/PHARMACEUTICS14061223
Abstract: The multi-inlet vortex mixer (MIVM) has emerged as a novel bottom-up technology for solid nanoparticle preparation. However, its performance in liposome preparation remains unknown. Here, two key process parameters (aqueous/organic flow rate ratio (FRR) and total flow rate (TFR)) of MIVM were investigated for liposome preparation. For this study, two model drugs (lysozyme and erythromycin) were chosen for liposome encapsulation as the representative hydrophilic and hydrophobic drugs, respectively. In addition, two modified MIVMs, one with herringbone-patterned straight inlets and one with zigzag inlets, were designed to further improve the mixing efficiency, aiming to achieve better drug encapsulation. Data showed that FRR played an important role in liposome size control, and a size of nm was achieved by FRR higher than 3:1. Moreover, increasing TFR (from 1 to 100 mL/min) could further decrease the size at a given FRR. However, similar regularities in controlling the encapsulation efficiency (EE%) were only noted in erythromycin-loaded liposomes. Modified MIVMs improved the EE% of lysozyme-loaded liposomes by 2~3 times at TFR = 40 mL/min and FRR = 3:1, which was consistent with computational fluid dynamics simulations. In summary, the good performance of MIVM in the control of particle size and EE% makes it a promising tool for liposome preparation, especially for hydrophobic drug loading, at flexible production scales.
Publisher: Mary Ann Liebert Inc
Date: 04-2017
Abstract: Mechanically ventilated patients commonly suffer from ventilator-associated pneumonia, hypoxemia, and other lower respiratory tract infection as a result of pathogen colonization and poor sputum clearance. Consequently, there is a high rate of morbidity and mortality in these patients. Dry powder mannitol increases sputum clearance, and therefore, we developed a system to administer it to mechanically ventilated patients without disconnection from the ventilator. The inspiratory line from a ventilator was split by using a three-way valve into two parallel lines where one contains a humidifier for normal breathing cycle and the other line contains a dry powder inhaler (Osmohaler™). The inspiratory air went through the dry powder line and aerosolized the mannitol powder only when its administration to a patient is required. We determined the delivered dose and particle size distributions of emitted aerosols in vitro from 9.5 mm endotracheal and 7.5 mm tracheostomy tubes, with inspiratory airflow of 60, 70, and 80 L/min. This novel setup was able to deliver 24.6% ± 3.33% of the 160 mg loaded dose mannitol powder (4 × 40 mg capsules) and 26.7% ± 2.19% of the 320 mg dose (4 × 80 mg capsules) when the endotracheal tube was used. With the shorter tracheostomy tube, the delivery dose increased to 35.6% ± 3.01% and 39.5% ± 2.04% of the 160 and 320 mg doses, respectively. The volume median diameters of the aerosols were in the respirable range with the largest value being 5.17 ± 0.87 μm. This delivery system has been shown to consistently deliver a high respirable dose of mannitol powder. Since this setup does not require disconnection of patients from the ventilator, it is safer for hypoxemic patients and easier to be adapted in a real clinical use.
Publisher: Informa UK Limited
Date: 04-2013
DOI: 10.1051/LHB/2013017
Publisher: Inderscience Publishers
Date: 2009
Publisher: Mary Ann Liebert Inc
Date: 04-2016
Publisher: Springer Science and Business Media LLC
Date: 12-04-2014
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.ADDR.2021.114078
Abstract: Antimicrobial resistance is a normal evolutionary process for microorganisms. Antibiotics exerted accelerated selective pressure that hasten bacterial resistance through mutation, and acquisition external genes. These genes often carry multiple antibiotic resistant determinants allowing the recipient microbe an instant "super-bug" status. The extent of Antimicrobial Resistance (AMR) has reached a level of global crisis, existing antimicrobials are no long effective in treating infections caused by AMR pathogens. The great majority of clinically available antimicrobial agents are administered through oral and intra-venous routes. Overcoming antibacterial resistance by novel drug delivery approach offered new hopes, particularly in the treatment of AMR pathogens in sites less assessible through systemic circulation such as the lung and skin. In the current review, we will revisit the mechanism and incidence of important AMR pathogens. Finally, we will discuss novel drug delivery approaches including novel local antibiotic delivery systems, hybrid antibiotics, and nanoparticle-based antibiotic delivery systems.
Publisher: Mary Ann Liebert Inc
Date: 02-2015
Abstract: A fatal incident was reported when a mechanical ventilated patient received nebulization of a reconstituted Relenza This is a bench study demonstrating the feasibility of a delivery system to introduce dry powder of Relenza to intubated patients. A dry powder inhaler placed within a delivery chamber was actuated by compressing a ventilation bag to disperse powder into a tracheal tube. The performance of two inhalers, a Diskhaler The efficiency of Osmohaler in delivering Relenza to the distal end [delivered dose=30.2±0.2% and fine particle fraction (FPF)=14.5±1.7%] was significantly higher than the Diskhaler (delivered dose=18.1±4.7% and FPF=3.4±2.1%). While no differences in the delivered dose and FPF were observed between the tracheostomy and endotracheal tubes of the same internal diameter, a larger endotracheal tube (9.0 mm internal diameter) gave a 6% higher FPF compared with the smaller counterpart (7.0 mm internal diameter). The dry powder delivery system has been demonstrated to be capable of delivering Relenza formulation to the distal end of tracheal tubes with a reasonable delivered dose and FPF. It would be necessary for further investigation into incorporating the proposed powder delivery system within a mechanical ventilator, as well as animal and clinical studies to prove its applicability to deliver zanamivir dry powder to ventilated influenza patients in the intensive care setting.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.ADDR.2021.113864
Abstract: Bacteriophages (Phages) are antibacterial viruses that are unaffected by antibiotic drug resistance. Many Phase I and Phase II phage therapy clinical trials have shown acceptable safety profiles. However, none of the completed trials could yield data supporting the promising observations noted in the experimental phage therapy. These trials have mainly focused on phage suspensions without enough attention paid to the stability of phage during processing, storage, and administration. This is important because in vivo studies have shown that the effectiveness of phage therapy greatly depends on the ratio of phage to bacterial concentrations (multiplicity of infection) at the infection site. Additionally, bacteria can evade phages through the development of phage-resistance and intracellular residence. This review focuses on the use of phage therapy against bacteria that survive within the intracellular niches. Recent research on phage behavior reveals that some phage can directly interact with, get internalized into, and get transcytosed across mammalian cells, prompting further research on the governing mechanisms of these interactions and the feasibility of harnessing therapeutic phage to target intracellular bacteria. Advances to improve the capability of phage attacking intracellular bacteria using formulation approaches such as encapsulating/conjugating phages into/with vector carriers via liposomes, polymeric particles, inorganic nanoparticles, and cell penetrating peptides, are summarized. While promising progress has been achieved, research in this area is still in its infancy and warrants further attention.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Elsevier BV
Date: 10-2020
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.XPHS.2017.02.014
Abstract: Aerosols emitted from metered dose inhalers (MDIs) are generally electrically charged and bipolar in nature. Although a spacer can effectively d en the charge magnitude of aerosols, the electrostatic interactions between the positively and negatively charged particles and the spacer have not yet been characterized separately. The Bipolar Charge Analyzer (BOLAR) was employed to investigate interactions between the spacer and the charged aerosols. Three in idual actuations of Tilade
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.ADDR.2014.10.022
Abstract: Respiratory infections represent a major global health problem. They are often treated by parenteral administrations of antimicrobials. Unfortunately, systemic therapies of high-dose antimicrobials can lead to severe adverse effects and this calls for a need to develop inhaled formulations that enable targeted drug delivery to the airways with minimal systemic drug exposure. Recent technological advances facilitate the development of inhaled anti-microbial therapies. The newer mesh nebulisers have achieved minimal drug residue, higher aerosolisation efficiencies and rapid administration compared to traditional jet nebulisers. Novel particle engineering and intelligent device design also make dry powder inhalers appealing for the delivery of high-dose antibiotics. In view of the fact that no new antibiotic entities against multi-drug resistant bacteria have come close to commercialisation, advanced formulation strategies are in high demand for combating respiratory 'super bugs'.
Publisher: Wiley
Date: 03-08-2022
DOI: 10.5694/MJA2.51674
Abstract: Traumatic brain injury (TBI) is the largest contributor to death and disability in people who have experienced physical trauma. There are no national data on outcomes for people with moderate to severe TBI in Australia. To determine the incidence and key determinants of outcomes for patients with moderate to severe TBI, both for Australia and for selected population subgroups, including Aboriginal and Torres Strait Islander Australians. The Australian Traumatic Brain Injury National Data (ATBIND) project will analyse Australia New Zealand Trauma Registry (ATR) data and National Coronial Information Service (NCIS) deaths data. The ATR documents the demographic characteristics, injury event description and severity, processes of care, and outcomes for people with major injury, including TBI, assessed and managed at the 27 major trauma services in Australia. We will include data for people with moderate to severe TBI (Abbreviated Injury Scale [AIS] (head) score higher than 2) who had Injury Severity Scores [ISS] higher than 12 or who died in hospital. People will also be included if they died before reaching a major trauma service and the coronial report details were consistent with moderate to severe TBI. The primary research outcome will be survival to discharge. Secondary outcomes will be hospital discharge destination, hospital length of stay, ventilator-free days, and health service cost. The Alfred Ethics Committee approved ATR data extraction (project reference number 670/21). Further ethics approval has been sought from the NCIS and multiple Aboriginal health research ethics committees. The ATBIND project will conform with Indigenous data sovereignty principles. Our findings will be disseminated by project partners with the aim of informing improvements in equitable system-level care for all people in Australia with moderate to severe TBI. Not applicable.
Publisher: American Chemical Society (ACS)
Date: 08-04-2021
Publisher: MDPI AG
Date: 08-09-2022
Abstract: Severe injury and chronic conditions require long-term management by multidisciplinary teams. Appropriate discharge planning ensures ongoing care to mitigate the long-term impact of injuries and chronic conditions. However, First Nations peoples in Australia face ongoing barriers to aftercare. This systematic review will locate and analyse global evidence of discharge interventions that have been implemented to improve aftercare and enhance health outcomes among First Nations people with an injury or chronic condition. A systematic search will be conducted using five databases, Google, and Google scholar. Global studies published in English will be included. We will analyse aftercare interventions implemented and the health outcomes associated. Two independent reviewers will screen and select studies and then extract and analyse the data. Quality appraisal of the included studies will be conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. The proposed study will analyse global evidence on discharge interventions that have been implemented for First Nations people with an injury or chronic conditions and their associated health outcomes. Our findings will guide healthcare quality improvement to ensure Aboriginal and Torres Strait Islander peoples have ongoing access to culturally safe aftercare services.
Publisher: British Editorial Society of Bone & Joint Surgery
Date: 10-2022
DOI: 10.1302/2046-3758.1110.BJR-2021-0495.R3
Abstract: Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models. Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted. A total of 43 studies were included. Animal models used included fracture-related infections (ten studies), periprosthetic joint infections (five studies), spinal infections (three studies), other implant-associated infections, and osteomyelitis. The most common bacteria were Staphylococcus species. Biofilm was most often observed with scanning electron microscopy. The natural history of biofilm revealed that the process of bacteria attachment, proliferation, maturation, and dispersal would take 14 days. For systemic mono-antibiotic therapy, only two of six studies using vancomycin reported significant biofilm reduction, and none reported eradication. Ten studies showed that combined systemic and topical antibiotics are needed to achieve higher biofilm reduction or eradication, and the effect is decreased with delayed treatment. Overall, 13 studies showed promising therapeutic potential with surface coating and antibiotic loading techniques. Combined topical and systemic application of antimicrobial agents effectively reduces biofilm at early stages. Future studies with sustained release of antimicrobial and biofilm-dispersing agents tailored to specific pathogens are warranted to achieve biofilm eradication. Cite this article: Bone Joint Res 2022 (10):700–714.
Publisher: Springer Science and Business Media LLC
Date: 27-09-2016
DOI: 10.1208/S12248-016-9988-9
Abstract: The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 μm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer® with the same configuration (single pin and one-third air inlet) that accommodates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5-2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer® inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections.
Publisher: American Chemical Society (ACS)
Date: 07-07-2021
Publisher: Elsevier BV
Date: 06-2018
Publisher: Elsevier BV
Date: 04-2013
Publisher: American Chemical Society (ACS)
Date: 23-05-2007
DOI: 10.1021/LA7006843
Abstract: Gold nanoparticles are one of the popular nanomaterials, widely used in biosensor applications as well as nanostructure construction. An essential attribute of these gold nanoparticles (Au-nps) is their stabilization against salt-induced aggregation. In this work, utilization of deoxyribonucleotides (dNTPs) as a tunable surface-stabilization agent for Au-nps was investigated. It was found that surfaces of Au-nps are covered by a layer of dNTPs after an adequate incubation with dNTPs solutions. Electrostatic repulsion among dNTP-coated Au-nps could prevent aggregation of Au-nps at a high salt concentration. The strength of dNTP-based protection can be manipulated by changing preparation protocols (e.g., incubation temperature, ionic strength, and ratio of Au-nps to dNTPs). Four different types of dNTPs exhibit different binding affinity to Au-nps and thus various stabilization efficiency in the order of dATP > dCTP > dGTP approximately dTTP. Moreover, this salt-induced aggregation can be reinitiated by the increase of solution temperature, which leads to a partial removal of the protective dNTP layer on Au-nps. The advantage of thermally tunable aggregation/dispersion of Au-nps mediated by dNTP adsorption offers a useful approach for the preparation of biomolecule (oligonucleotides and oligopeptides) modified nanoparticles in applications of bioassay and nanobiotechnology.
Publisher: Elsevier BV
Date: 10-2020
No related grants have been discovered for Sharon Leung.