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Toward understanding polymer micelle stability: Density ultracentrifugation offers insight into polymer micelle stability in human fluids.
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2019-12-24 , DOI: 10.1016/j.jconrel.2019.12.038 Timothy D Langridge 1 , Richard A Gemeinhart 2
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2019-12-24 , DOI: 10.1016/j.jconrel.2019.12.038 Timothy D Langridge 1 , Richard A Gemeinhart 2
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Micelles, as a class of drug delivery systems, are underrepresented among United States Food and Drug Administration approved drugs. A lack of clinical translation of these systems may be due to, in part, to a lack of understanding of micelle interactions with biologic fluids following injection. Despite the limited clinical translation, micelles remain an active area of research focus and pre-clinical development. The goal of the present study was to examine the stability of amphiphilic block copolymer micelles in biologic fluids to identify the properties and components of biologic fluids that influence micelle stability. Micelle stability, measured via Förster resonance energy transfer-based fluorescent spectrometry, was complemented with density ultracentrifugation to reveal the colocalized, or dissociated, state of the dye cargo after exposure to human biologic fluids. Polymeric micelles composed of poly(ethylene glycol-block-caprolactone) (mPEG-CL) and poly(ethylene glycol-block-lactide) (mPEG-LA) were unstable in fetal bovine serum, human serum and synovial fluid, with varying levels of instability observed in ascites and pleural fluid. All polymeric micelles exhibited stability in cerebrospinal fluid, highlighting the potential for local cerebro-spinal administration of micelles. Interestingly, mPEG2.2k-CL3.1k and mPEG2k-LA2.7k micelles favored dissolution whereas mPEG5.4k-LA28.5k micelles favored stability. Taken together, our data offers both quantitative and qualitative evidence for micelle stability within human biologic fluids and offers evidence of polymer micelle instability in biologic fluids that is not explained by either total protein content or total unsaturated lipid content. The results help to identify potential sites for local delivery where stability is maintained.
中文翻译：
理解聚合物胶束稳定性：密度超速离心可以深入了解人体液体中聚合物胶束的稳定性。
胶束作为一类药物递送系统，在美国食品和药物管理局批准的药物中代表性不足。这些系统缺乏临床转化可能部分是由于缺乏对注射后胶束与生物液体相互作用的了解。尽管临床转化有限，但胶束仍然是研究重点和临床前开发的活跃领域。本研究的目的是检查两亲性嵌段共聚物胶束在生物液体中的稳定性，以确定影响胶束稳定性的生物液体的性质和成分。通过基于福斯特共振能量转移的荧光光谱法测量胶束稳定性，并辅以密度超速离心，以揭示染料货物暴露于人体生物液体后的共定位或解离状态。由聚乙二醇嵌段己内酯（mPEG-CL）和聚乙二醇嵌段丙交酯（mPEG-LA）组成的聚合物胶束在胎牛血清、人血清和滑液中不稳定，具有不同水平的腹水和胸腔积液中观察到不稳定。所有聚合物胶束在脑脊液中均表现出稳定性，凸显了胶束局部脑脊髓给药的潜力。有趣的是，mPEG2.2k-CL3.1k 和 mPEG2k-LA2.7k 胶束有利于溶解，而 mPEG5.4k-LA28.5k 胶束有利于稳定性。总而言之，我们的数据提供了人类生物液中胶束稳定性的定量和定性证据，并提供了生物液中聚合物胶束不稳定性的证据，这种不稳定性不能用总蛋白质含量或总不饱和脂质含量来解释。 结果有助于确定保持稳定的本地交付的潜在地点。
更新日期：2019-12-25
中文翻译：
理解聚合物胶束稳定性：密度超速离心可以深入了解人体液体中聚合物胶束的稳定性。
胶束作为一类药物递送系统，在美国食品和药物管理局批准的药物中代表性不足。这些系统缺乏临床转化可能部分是由于缺乏对注射后胶束与生物液体相互作用的了解。尽管临床转化有限，但胶束仍然是研究重点和临床前开发的活跃领域。本研究的目的是检查两亲性嵌段共聚物胶束在生物液体中的稳定性，以确定影响胶束稳定性的生物液体的性质和成分。通过基于福斯特共振能量转移的荧光光谱法测量胶束稳定性，并辅以密度超速离心，以揭示染料货物暴露于人体生物液体后的共定位或解离状态。由聚乙二醇嵌段己内酯（mPEG-CL）和聚乙二醇嵌段丙交酯（mPEG-LA）组成的聚合物胶束在胎牛血清、人血清和滑液中不稳定，具有不同水平的腹水和胸腔积液中观察到不稳定。所有聚合物胶束在脑脊液中均表现出稳定性，凸显了胶束局部脑脊髓给药的潜力。有趣的是，mPEG2.2k-CL3.1k 和 mPEG2k-LA2.7k 胶束有利于溶解，而 mPEG5.4k-LA28.5k 胶束有利于稳定性。总而言之，我们的数据提供了人类生物液中胶束稳定性的定量和定性证据，并提供了生物液中聚合物胶束不稳定性的证据，这种不稳定性不能用总蛋白质含量或总不饱和脂质含量来解释。 结果有助于确定保持稳定的本地交付的潜在地点。
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