Effect of mPEG-PLGA on Drug Crystallinity and Release of Long-Acting Injection Microspheres: In Vitro and In Vivo Perspectives.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY Pharmaceutical Research Pub Date : 2024-06-01 Epub Date: 2024-06-05 DOI:10.1007/s11095-024-03717-y

Dandan Xing, Lihua Tang, Hongyu Yang, Mingjiao Yan, Panao Yuan, Yulan Wu, Yu Zhang, Tian Yin, Yanjiao Wang, Jingxin Gou, Xing Tang, Haibing He

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Abstract

Purpose: Traditional progesterone (PRG) injections require long-term administration, leading to poor patient compliance. The emergence of long-acting injectable microspheres extends the release period to several days or even months. However, these microspheres often face challenges such as burst release and incomplete drug release. This study aims to regulate drug release by altering the crystallinity of the drug during the release process from the microspheres.

Methods: This research incorporates methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide) (mPEG-PLGA) into poly(lactide-co-glycolide) (PLGA) microspheres to enhance their hydrophilicity, thus regulating the release rate and drug morphology during release. This modification aims to address the issues of burst and incomplete release in traditional PLGA microspheres. PRG was used as the model drug. PRG/mPEG-PLGA/PLGA microspheres (PmPPMs) were prepared via an emulsification-solvent evaporation method. Scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC) were employed to investigate the presence of PRG in PmPPMs and its physical state changes during release.

Results: The addition of mPEG-PLGA altered the crystallinity of the drug within the microspheres at different release stages. The crystallinity correlated positively with the amount of mPEG-PLGA incorporated; the greater the amount, the faster the drug release from the formulation. The bioavailability and muscular irritation of the long-acting injectable were assessed through pharmacokinetic and muscle irritation studies in Sprague-Dawley (SD) rats. The results indicated that PmPPMs containing mPEG-PLGA achieved low burst release and sustained release over 7 days, with minimal irritation and self-healing within this period. PmPPMs with 5% mPEG-PLGA showed a relative bioavailability (Frel) of 146.88%.

In conclusion: In summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.

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mPEG-PLGA 对长效注射微球药物结晶度和释放的影响：体外和体内观察

目的：传统的黄体酮（PRG）注射剂需要长期服用，导致患者依从性差。长效注射微球的出现将释放期延长至数天甚至数月。然而，这些微球经常面临药物猝发释放和不完全释放等挑战。本研究旨在通过改变药物在微球释放过程中的结晶度来调节药物释放：本研究将甲氧基聚（乙二醇）-b-聚（乳酸-共聚乙二醇）（mPEG-PLGA）加入聚（乳酸-共聚乙二醇）（PLGA）微球中，以增强其亲水性，从而调节释放速率和释放过程中的药物形态。这种改性旨在解决传统 PLGA 微球中的猝灭和不完全释放问题。以 PRG 为模型药物。通过乳化-溶剂蒸发法制备了 PRG/mPEG-PLGA/PLGA 微球（PmPPMs）。采用扫描电子显微镜（SEM）、粉末 X 射线衍射（PXRD）和差示扫描量热法（DSC）研究了 PRG 在 PmPPMs 中的存在及其在释放过程中的物理状态变化：结果：在不同释放阶段，mPEG-PLGA 的加入改变了微球中药物的结晶度。结晶度与 mPEG-PLGA 的添加量呈正相关；添加量越大，药物从制剂中释放的速度越快。通过对 Sprague-Dawley (SD) 大鼠进行药代动力学和肌肉刺激性研究，评估了长效注射剂的生物利用度和肌肉刺激性。结果表明，含有 mPEG-PLGA 的 PmPPMs 实现了低猝灭释放和 7 天的持续释放，在此期间刺激性极小且可自我修复。含有 5% mPEG-PLGA 的 PmPPMs 的相对生物利用度（Frel）为 146.88%：总之，在 PLGA 微球中添加适量的 mPEG 可以改变药物释放过程并提高生物利用度。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.