Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release.
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ABSTRACT:
SUBMITTER: Dong N
PROVIDER: S-EPMC7327764 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Project description:At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high-risk environment, long-term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long-acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l-lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release system for long-term AIDS prevention. As the HIV membrane fusion inhibitor (LP-98) used in this research is amphiphilic lipopeptide, W1/O/W2 double-emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP-98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP-98-loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained-release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.
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Project description:The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4-by-5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~39 μm) across five groups with different alginate: NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loading %. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate: NaHCO3 = 1 exhibited rough and porous surfaces, high Young's modulus, and hardness. In each group with the same alginate: NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relatively high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relatively high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relatively high NaHCO3 concentrations improved the cytotoxicity effects in vitro.
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