Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration, which usually demands appropriate carriers like microspheres (MS) to control drugs releases. Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate. In this study, we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres, with smaller poly(lactic-co-glycolic acid) MS (∼8–10 μm in diameter) embedded in a larger chitosan MS (∼250–300 μm in diameter). The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage. Two kinds of model drugs, bovine serum albumin and chlorhexidine acetate, were encapsulated in the microspheres. The fluorescence-labeled rhodamine-fluoresceine isothiocyanate (Rho-FITC) and ultraviolet (UV) spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres, as well as sustained, slow release in vitro. In addition, far-UV circular dichroism and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) results indicated original secondary structure and molecular weight of drugs after electrospraying. Generally speaking, our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded, which could be applied in sequential, multi-modality therapy.

中文翻译：

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分层电喷雾PLGA @壳聚糖球内复合微球，实现多药控释。

顺序给药和不同药物的控释对于调节细胞行为和组织再生至关重要，这通常需要像微球（MS）这样的合适载体来控制药物的释放。电喷雾已被证明是制备粒径均匀，载药率高的质谱的有效技术。在这项研究中，我们将电喷雾技术应用于简单且分层地制造球内复合微球，其中较小的聚乳酸-乙醇酸共聚物（直径约8–10μm）嵌入较大的壳聚糖MS（约250）中直径–300μm）。扫描电子显微镜图像显示可以通过调节喷嘴直径或电压来精确控制的高度均匀的质谱。两种模型药物，牛血清白蛋白和醋酸洗必泰，被包裹在微球中。荧光标记的若丹明-异硫氰酸荧光素（Rho-FITC）和紫外（UV）分光光度法的结果表明，负载的药物在微球中具有出色的分布，并且持续，缓慢释放体外。此外，远紫外圆二色性和基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF-MS）结果表明，电喷雾后药物的原始二级结构和分子量。总体而言，我们的研究提出了一种改进的分层电喷雾技术，以制备载有两种不同药物的球内复合材料MS，该技术可用于序贯的多模态治疗。