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首页> 美国卫生研究院文献>Progress in Biomaterials >An integrated experimental and modeling approach to propose biotinylated PLGA microparticles as versatile targeting vehicles for drug delivery
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An integrated experimental and modeling approach to propose biotinylated PLGA microparticles as versatile targeting vehicles for drug delivery

机译：提出将生物素化PLGA微粒作为多功能靶向载体进行药物递送的综合实验和建模方法

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Polymeric microparticles with covalently attached biotin are proposed as versatile targeting vehicles for drug delivery. The proposed microparticles made of 85/15 poly (lactic-co-glycolic acid) (PLGA) will have biotin available on the outside of the particle for the further attachment with an avidin group. Taking advantage of biotin’s high affinity for avidin, and avidin’s well-known chemistry, the particle has the potential to be easily coated with a variety of targeting moieties. This paper focuses on the design and resulting effect of adding biotin to PLGA microparticles using an integrated experimental and modeling approach. A fluorescent-tagged avidin (488-streptavidin) was used to confirm the presence and bioavailability of biotin on the outside of the particles. For the purpose of this study, bovine serum albumin (BSA) was used as a model therapeutic drug. Microparticles were created using two different types of polyvinyl alcohol 88 and 98 mol% hydrolyzed, which were then analyzed for their size, morphology, and encapsulation capacity of BSA. Release studies performed in vitro confirmed the slow release of the BSA over a 28-day period. Based on these release profiles, a release kinetics model was used to further quantify the effect of biotinylation of PLGA microparticles on their release characteristics by quantitatively extracting the effective drug diffusivity and drug desorption rate from the release profiles. It was found that the biotinylation of the PLGA microparticles slowed down both the drug desorption and drug diffusion process, which confirmed that biotinylated PLGA microparticles can be used for controlled drug release. The presented technology, as well as the proposed integrated experimental and modeling approach, forms a solid foundation for future studies using a cell-specific ligand that can be attached to avidin and incorporated onto the microparticles for targeted delivery.Electronic supplementary materialThe online version of this article (doi:10.1186/2194-0517-2-3) contains supplementary material, which is available to authorized users.
机译：具有共价连接的生物素的聚合物微粒被提议作为用于药物递送的通用靶向载体。拟议的由85/15聚乳酸-乙醇酸共聚物（PLGA）制成的微粒将在微粒的外部具有生物素，可与亲和素基团进一步结合。利用生物素对亲和素的高度亲和力和亲和素的众所周知的化学作用，这种颗粒具有很容易被各种靶向部分覆盖的潜力。本文着重于使用集成的实验和建模方法将生物素添加到PLGA微粒中的设计及其产生的效果。使用荧光标记的抗生物素蛋白（488-链霉亲和素）来确认生物素在颗粒外部的存在和生物利用度。出于这项研究的目的，牛血清白蛋白（BSA）被用作模型治疗药物。使用两种不同类型的水解的聚乙烯醇88和98 mol％产生微粒，然后分析它们的大小，形态和BSA的封装能力。体外进行的释放研究证实了BSA在28天的时间内缓慢释放。基于这些释放曲线，通过从释放曲线中定量提取有效药物扩散率和药物解吸速率，可使用释放动力学模型进一步量化PLGA微粒生物素化对其释放特性的影响。发现PLGA微粒的生物素化减慢了药物的解吸和药物扩散过程，这证实了生物素化的PLGA微粒可用于控制药物的释放。所提出的技术以及拟议的集成实验和建模方法，为使用细胞特异性配体的未来研究奠定了坚实的基础，该配体可以连接至抗生物素蛋白并掺入微粒中以进行靶向递送。文章（doi：10.1186 / 2194-0517-2-3）包含补充材料，授权用户可以使用。

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