可生物降解聚酯微球控制多肽和蛋白质的释放:一种治疗传染病和恶性肿瘤的方法

Smadar Cohen , Limor Chen , Ron N Apte
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引用次数: 23

摘要

本文描述了一种增强疟疾肽基疫苗免疫原性和重组人白细胞介素-1α (IL-1)免疫调节活性的方法。该方法包括将这些分子封装在乳酸和乙醇酸(PLGA)的可生物降解聚酯微球中,并控制其释放。采用基于双乳液的改性溶剂蒸发法制备微球。为每个分子构建了两种不同分子量的由PLGA(75:25乳酸/乙醇酸)组成的微球。利用光谱学和生物活性分析评价了这些分子在微球中的释放特性。体内研究证实了PLGA载体作为疟疾多肽疫苗免疫载体的可行性;小鼠诱导的免疫应答比完全弗氏佐剂中的肽更强。此外,这些研究提供了初步证据,表明包裹IL-1的PLGA微球可以作为一种新的策略,在免疫治疗中将IL-1细胞因子有效地递送到肿瘤部位。
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Controlled release of peptides and proteins from biodegradable polyester microspheres: an approach for treating infectious diseases and malignancies

An approach to enhance the immunogenicity of peptide-based vaccines for malaria and the immunoregulatory activity of recombinant human interleukin-1α (IL-1) is described. The approach involves the encapsulation of these molecules in, and their controlled release from, biodegradable polyester microspheres of lactic and glycolic acids (PLGA). The microspheres are prepared by the modified solvent evaporation method based on a double emulsion. Two types of microspheres composed of PLGA (75:25 lactic/glycolic acid) and of different MW were constructed for each molecule. The release characteristics of these molecules from these microspheres were evaluated using spectroscopy and bioactivity assays. In vivo studies established the feasibility of PLGA carriers as an immunization vehicle for malaria peptide-based vaccines; the induced immune responses in mice were stronger than those obtained with peptide in complete Freund's adjuvant. In addition, these studies provide preliminary evidence that PLGA microspheres with encapsulated IL-1 can be used as a new strategy for the efficient delivery of this cytokine to tumor sites in immunotherapy.

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