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首页> 外文学位 >Experimental and computational investigations of therapeutic drug release from biodegradable poly(lactide-co-glycolide) (PLG) microspheres.
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Experimental and computational investigations of therapeutic drug release from biodegradable poly(lactide-co-glycolide) (PLG) microspheres.

机译：从可生物降解的聚（丙交酯-共-乙交酯）（PLG）微球释放治疗性药物的实验和计算研究。

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摘要

The need to tailor release-rate profiles from polymeric microspheres remains one of the leading challenges in controlled drug delivery. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In addition, drug release rate from polymeric microspheres is dependent on material properties such as polymer molecular weight. Mathematical modeling provides insight into the fundamental processes that govern the release, and once validated with experimental results, it can be used to tailor a desired controlled drug delivery system.;To these ends, PLG microspheres were fabricated using the oil-in-water emulsion technique. A quantitative study that describes the size distribution of poly(lactide-coglycolide) (PLG) microspheres is presented. A fluid mechanics-based correlation that predicts the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow. The effects of microspheres' mean diameter, polydispersity, and polymer molecular weight on therapeutic drug release rate from poly(lactide-co-glycolide) (PLG) microspheres were investigated experimentally. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. In addition, a numerical optimization technique, based on the least squares method, was developed to achieve desired therapeutic drug release profiles by combining individual microsphere populations.;The fluid mechanics-based mathematical correlation that predicts microsphere mean diameter provided a close fit to the experimental results. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. Using the numerical optimization technique, it was possible to achieve desired release profiles, in particular zero-order and pulsatile release, by combining individual microsphere populations at the appropriate proportions.;Overall, this work shows that engineering polymeric microsphere populations having predetermined characteristics is an effective means to obtain desired therapeutic drug release patterns, relevant for controlled drug delivery.
机译：定制聚合物微球的释放速率分布的需要仍然是受控药物递送中的主要挑战之一。对药物释放速率有重大影响的微球尺寸可以潜在地改变，以设计具有所需释放曲线的受控药物输送系统。另外，聚合物微球的药物释放速率取决于材料性能，例如聚合物分子量。数学模型提供了控制释放的基本过程的见解，并在通过实验结果验证后，可用于定制所需的受控药物递送系统。为此，使用水包油型乳液制备了PLG微球。技术。定量研究描述了聚丙交酯-乙交酯（PLG）微球的大小分布。基于湍流中的乳化理论，基于流体力学的相关性可预测平均微球直径。实验研究了微球的平均直径，多分散度和聚合物分子量对聚丙交酯-共-乙交酯（PLG）微球的治疗药物释放速率的影响。基于实验结果，已开发出一种合适的数学理论，其中纳入了微球尺寸分布和聚合物降解对药物释放的影响。此外，还开发了一种基于最小二乘法的数值优化技术，以通过组合各个微球种群来获得所需的治疗药物释放曲线。;基于流体力学的数学相关性可预测微球的平均直径，与实验非常吻合结果。我们从体外释放实验表明，微球尺寸对药物释放速率有显着影响。随着微球尺寸的增加，初始释放速率降低。另外，随着微球尺寸的增加，释放曲线从一阶变为凹形向上（S形）。数学模型与实验释放数据非常吻合。使用数值优化技术，可以通过按适当比例组合各个微球种群来获得所需的释放曲线，尤其是零级和脉动释放。总体而言，这项工作表明，具有预定特性的工程聚合物微球种群是一种获得与控制药物递送有关的所需治疗药物释放模式的有效手段。

著录项

  • 作者

    Berchane, Nader Samir.;

  • 作者单位

    Texas A&M University.;

  • 授予单位 Texas A&M University.;
  • 学科 Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 142 p.
  • 总页数 142
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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