Department of Chemical and Biological Engineering, Iowa State University, Ames, Iowa 50011, USA.
Mol Pharm. 2012 Apr 2;9(4):874-82. doi: 10.1021/mp2004059. Epub 2012 Mar 20.
Advancements toward an improved vaccine against Bacillus anthracis, the causative agent of anthrax, have focused on formulations composed of the protective antigen (PA) adsorbed to aluminum hydroxide. However, due to the labile nature of PA, antigen stability is a primary concern for vaccine development. Thus, there is a need for a delivery system capable of preserving the immunogenicity of PA through all the steps of vaccine fabrication, storage, and administration. In this work, we demonstrate that biodegradable amphiphilic polyanhydride nanoparticles, which have previously been shown to provide controlled antigen delivery, antigen stability, immune modulation, and protection in a single dose against a pathogenic challenge, can stabilize and release functional PA. These nanoparticles demonstrated polymer hydrophobicity-dependent preservation of the biological function of PA upon encapsulation, storage (over extended times and elevated temperatures), and release. Specifically, fabrication of amphiphilic polyanhydride nanoparticles composed of 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane best preserved PA functionality. These studies demonstrate the versatility and superiority of amphiphilic nanoparticles as vaccine delivery vehicles suitable for long-term storage.
针对炭疽杆菌（导致炭疽病的病原体）的改良疫苗的研究进展主要集中在将保护性抗原（PA）吸附到氢氧化铝的配方上。然而，由于 PA 的不稳定性，抗原稳定性是疫苗开发的主要关注点。因此，需要一种能够在疫苗制造、储存和管理的所有步骤中保持 PA 免疫原性的递送系统。在这项工作中，我们证明了先前已经显示出能够提供受控抗原递送、抗原稳定性、免疫调节和单一剂量对抗病原体挑战的保护作用的生物可降解两亲性聚酸酐纳米粒子，能够稳定和释放功能性 PA。这些纳米粒子表现出聚合物疏水性依赖性的封装、储存（长时间和高温）和释放过程中 PA 生物功能的保存。具体来说，由 1,6-双（对羧基苯氧基）己烷和 1,8-双（对羧基苯氧基）-3,6-二氧辛烷组成的两亲性聚酸酐纳米粒子的制备能够最好地保存 PA 功能。这些研究表明了两亲性纳米粒子作为适合长期储存的疫苗递送载体的多功能性和优越性。
