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A combined reverse thermal gel-polymeric micelle system for sustained delivery of ophthalmic drugs.

机译：组合式逆向热凝胶-聚合物胶束系统，用于持续输送眼科药物。

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摘要

Delivery of drugs to the eye is a challenging endeavor due to the myriad anatomical and physiological barriers preventing intraocular absorption of molecules that either contact the anterior surfaces of the eye or are present in the bloodstream. Topical administration---the workhorse of ophthalmic drug delivery---suffers from numerous drawbacks including poor intraocular bioavailability, excessive systemic absorption, need for frequent re-administration and a reliance on patient adherence for therapeutic efficacy, among others. To overcome these limitations, researchers have explored various controlled release drug delivery systems with the ultimate goal of sustaining consistent, localized drug levels at the target tissue thereby maximizing therapeutic efficacy and minimizing unintended adverse effects. Among the options explored, in situ-gelling polymeric systems may hold the most promise due to their ability to be administered directly at the target site by a minimally-invasive injection and form a stable physical gel while conforming to the specific anatomy of that space. To date, clinical application of such systems has been hindered by their limited ability to sustain long-term delivery of drugs. To overcome this limitation, we sought to develop a system comprising a reverse thermal gel (RTG) encapsulating drug-loaded polymeric micelles as a combined system for the sustained local delivery of poorly soluble drugs. The polymers comprising the RTG and the micelles---both novel---were first independently characterized as free-standing systems. The combined system was then evaluated and was found to retain the injectability and in situ gelling characteristics of the thermal gel, but additionally benefited from the superior ability of the entrapped micelles to encapsulate and sustain release of the poorly soluble corticosteroid triamcinolone acetonide (TA). Release of TA from the combined system was completely free of a burst release and was projected to continue at a steady rate for approximately twelve months. To our knowledge, this system is the first in the literature to achieve delivery time frames from an in situ-gelling polymer beyond a few months and has the potential to significantly improve delivery of TA and, more broadly, clinical treatment of posterior ophthalmic diseases.
机译：由于无数的解剖学和生理学屏障阻止了眼内吸收与眼睛的前表面接触或存在于血液中的分子，因此将药物输送到眼睛是一项具有挑战性的努力。局部给药-眼科给药的主要手段-具有许多缺点，包括眼内生物利用度差，全身吸收过多，需要频繁重新给药以及依赖患者依从性以获得治疗功效等。为了克服这些局限性，研究人员探索了各种控释药物递送系统，其最终目的是在靶组织上维持一致的局部药物水平，从而使治疗效果最大化，并将意外不良反应降至最低。在探索的选择中，原位胶凝聚合物系统可能具有最大的前景，因为它们能够通过微创注射直接在靶部位给药，并形成稳定的物理凝胶，同时符合该空间的特定解剖结构。迄今为止，此类系统的临床应用受到其长期维持药物输送能力的限制。为了克服此限制，我们寻求开发一种系统，该系统包含封装载有药物的聚合物微团的逆向热凝胶（RTG），作为用于持续局部递送难溶性药物的组合系统。包含RTG和胶束的聚合物-都是新颖的-首先被独立表征为独立系统。然后评估组合系统，发现保留了热凝胶的可注射性和原位胶凝特性，但另外还受益于截留的胶束封装和维持难溶皮质类固醇三苯丙酮酸丙酮（TA）释放的卓越能力。从组合系统中释放TA完全没有突发性释放，并且预计将以稳定的速率持续约12个月。据我们所知，该系统是文献中第一个从原位胶凝聚合物中获得超过数月的递送时间框架的系统，并且具有显着改善TA递送以及更广泛地用于后眼疾病的临床治疗的潜力。

著录项

  • 作者

    Famili, Amin.;

  • 作者单位

    University of Colorado at Denver.;

  • 授予单位 University of Colorado at Denver.;
  • 学科 Engineering Biomedical.;Health Sciences Ophthalmology.;Engineering Materials Science.;Chemistry Polymer.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 178 p.
  • 总页数 178
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 石油、天然气工业;
  • 关键词

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