Jiang Wenlei, Gupta Rajesh K, Deshpande Mangesh C, Schwendeman Steven P
Pharmaceutical and Analytical Development, Novartis Pharmaceutical Corporation, One Health Plaza, East Hanover, NJ 07936, USA.
Adv Drug Deliv Rev. 2005 Jan 10;57(3):391-410. doi: 10.1016/j.addr.2004.09.003.
Injectable biodegradable polymeric particles (usually microspheres) represent an exciting approach to control the release of vaccine antigens to reduce the number of doses in the immunization schedule and optimize the desired immune response via selective targeting of antigen to antigen presenting cells. After the first couple of decades of their study, much progress has been made towards the clinical use of antigen-loaded microspheres. Poly(lactide-co-glycolic acids) (PLGAs) have been studied most commonly for this purpose because of their proven safety record and established use in marketed products for controlled delivery of several peptide drugs. PLGA microspheres have many desirable features relative to standard aluminum-based adjuvants, including the microspheres' ability to induce cell-mediated immunity, a necessary requirement for emergent vaccines against HIV and cancer. This review examines several impediments to PLGA microparticle development, such as PLGA-encapsulated antigen instability and deficiency of animal models in predicting human response, and describes new trends in overcoming these important issues. PLGA microparticles have displayed unprecedented versatility and safety to accomplish release of one or multiple antigens of varying physical-chemical characteristics and immunologic requirements, and have now met numerous critical benchmarks in development of long-lasting immunity after a single injected dose.
可注射的生物可降解聚合物颗粒（通常为微球）是一种令人兴奋的方法，可用于控制疫苗抗原的释放，以减少免疫接种计划中的剂量数量，并通过将抗原选择性靶向抗原呈递细胞来优化所需的免疫反应。在对其进行了最初几十年的研究之后，载有抗原的微球在临床应用方面取得了很大进展。聚乳酸-乙醇酸共聚物（PLGA）由于其已被证实的安全记录以及在市售的几种肽类药物控释产品中的既定用途，已成为最常用于此目的的研究对象。相对于标准的铝基佐剂，PLGA微球具有许多理想的特性，包括微球诱导细胞介导免疫的能力，这是针对HIV和癌症的新型疫苗的必要要求。本综述探讨了PLGA微粒开发的几个障碍，例如PLGA包裹的抗原不稳定性以及动物模型在预测人类反应方面的不足，并描述了克服这些重要问题的新趋势。PLGA微粒已显示出前所未有的多功能性和安全性，能够实现释放具有不同物理化学特性和免疫要求的一种或多种抗原，并且目前在单次注射剂量后产生持久免疫力的开发中已达到了众多关键基准。
