A spray drying technique was developed to prepare injectable and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres encapsulating a model luteinizing hormone-releasing hormone agonist (LHRHa)-based peptide, leuprolide. Various spray drying parameters were evaluated to prepare 1-month controlled release formulations with a similar composition to the commercial Lupron Depot® (LD). A single water-in-oil emulsion of aqueous leuprolide/gelatin solution in PLGA 75/25 acid capped (13 kDa Mw) dissolved in methylene chloride (DCM) was spray-dried before washing the microspheres in cold ddH2O and freeze-drying. The spray-drying microencapsulation was characterized by: particle size/distribution (span), morphology, drug/gelatin loading, encapsulation efficiency, and residual DCM and water content. Long-term release was tested over 9 weeks in PBS + 0.02% Tween 80 + 0.02% sodium azide pH 7.4 (PBST) at 37 °C. Several physical-chemical parameters were monitored simultaneously for selected formulations, including: water uptake, mass loss, dry and hydrated glass transition temperature, to help understand the related long-term release profiles and explore the underlying controlled-release mechanisms. Compared with the commercial LD microspheres, some of the in-house spray-dried microspheres presented highly similar or even improved long-term release profiles, providing viable long-acting release (LAR) alternatives to the LD. The in vitro release mechanism of the peptide was shown to be controlled either by kinetics of polymer mass loss or by a second process, hypothesized to involve peptide desorption from the polymer. These data indicate spray drying can be optimized to prepare commercially relevant PLGA microsphere formulations for delivery of peptides, including the LHRHa, leuprolide.

中文翻译：

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通过喷雾干燥将黄体生成素释放激素激动剂微囊化在聚（乳酸-乙醇酸）微球中。

开发了一种喷雾干燥技术来制备可注射和可生物降解的聚乳酸-乙醇酸 (PLGA) 微球，该微球封装了一种模型黄体生成素释放激素激动剂 (LHRHa) 基肽亮丙瑞林。对各种喷雾干燥参数进行了评估，以制备 1 个月的控释制剂，其成分与商业 Lupron Depot® (LD) 相似。将亮丙瑞林/明胶水溶液溶于二氯甲烷 (DCM) 的 PLGA 75/25 酸封端 (13 kDa Mw) 中形成的单一油包水乳液喷雾干燥，然后用冷 ddH2O 洗涤微球并冷冻干燥。喷雾干燥微胶囊的特征在于：粒径/分布（跨度）、形态、药物/明胶负载量、包封效率以及残留DCM和水含量。在 37 °C 的 PBS + 0.02% Tween 80 + 0.02% 叠氮化钠 pH 7.4 (PBST) 中测试了 9 周的长期释放。同时监测选定配方的几个物理化学参数，包括：吸水量、质量损失、干燥和水合玻璃化转变温度，以帮助了解相关的长期释放曲线并探索潜在的控释机制。与商业 LD 微球相比，一些内部喷雾干燥微球表现出高度相似甚至改进的长期释放曲线，为 LD 提供了可行的长效释放 (LAR) 替代品。肽的体外释放机制被证明是通过聚合物质量损失的动力学或通过第二个过程控制的，假设涉及肽从聚合物的解吸。这些数据表明可以优化喷雾干燥以制备商业相关的 PLGA 微球制剂，用于递送肽，包括 LHRHa、亮丙瑞林。