Department of Pharmaceutics Science, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China.
Department of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Pharm Res. 2024 Jun;41(6):1271-1284. doi: 10.1007/s11095-024-03717-y. Epub 2024 Jun 5.
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.
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.
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 summary, adding an appropriate amount of mPEG to PLGA microspheres can alter the drug release process and enhance bioavailability.
传统孕激素（PRG）注射需要长期给药，导致患者顺应性差。长效注射微球的出现将释放期延长至数天甚至数月。然而，这些微球在释放过程中经常面临突释和药物不完全释放等挑战。本研究旨在通过改变微球释放过程中药物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-乙醇酸）（mPEG-PLGA）掺入聚（乳酸-共-乙醇酸）（PLGA）微球中，以提高其亲水性，从而调节释放过程中的释放速率和药物形态。这种修饰旨在解决传统 PLGA 微球中突释和不完全释放的问题。PRG 被用作模型药物。通过乳化-溶剂蒸发法制备 PRG/mPEG-PLGA/PLGA 微球（PmPPMs）。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）用于研究 PmPPMs 中 PRG 的存在及其在释放过程中物理状态的变化。
mPEG-PLGA 的加入改变了微球在不同释放阶段药物的结晶度。结晶度与掺入的 mPEG-PLGA 量呈正相关；掺入量越大，药物从制剂中的释放速度越快。通过 Sprague-Dawley（SD）大鼠的药代动力学和肌肉刺激研究评估了长效注射的生物利用度和肌肉刺激性。结果表明，含有 mPEG-PLGA 的 PmPPMs 实现了低突释和 7 天持续释放，在此期间刺激最小且具有自我修复能力。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。
