Enhanced stability of horseradish peroxidase encapsulated in acetalated dextran microparticles stored outside cold chain conditions

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• 作者：Naveen Kanthamneni^a ; ¹ ; Sadhana Sharma^a ; ¹ ; Samantha A. Meenach^a ; Beau Billet^b ; Ji-Cheng Zhao^b ; Eric M. Bachelder^a ; Kristy M. Ainslie^a ; ^{ainslie@pharmacy.ohio-state.edu}
• 关键词：PLGA ; polylactic-co-glycolic acid ; Ac-DEX ; acetalated dextran ; MW ; molecular weight ; 71k ; 71 ; 400 molecular weight ; HRP ; horseradish peroxidase ; DCs ; dendritic cells ; DCM ; dichloromethane ; PBS ; phosphate buffered saline ; PVA ; poly(vinyl alcohol) ; BCA ; bici
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：15 July, 2012
• 卷：431
• 期：1-2
• 页码：101-110
• 文件大小：1762 K

摘要

Micro- and nanoparticles have been shown to improve the efficacy of safer protein-based (subunit) vaccines. Here, we evaluate a method of improving the vaccine stability outside cold chain conditions by encapsulation of a model enzyme, horseradish peroxidase (HRP), in an acid-sensitive, tunable biodegradable polymer, acetalated dextran (Ac-DEX). Vaccines that are stable outside the cold chain would be desirable for use in developing nations. Ac-DEX particles encapsulating HRP were prepared using two different methods, probe sonication and homogenization. These particles were stored under different storage conditions (鈭?0 掳C, 4 掳C, 25 掳C or 45 掳C) for a period of 3 months. On different days, the particles were characterized for various physical and chemical measurements. At all conditions, Ac-DEX particles remained spherical in nature, as compared to PLGA particles that fused together starting at day 3 at 45 掳C. Furthermore, our results indicated that encapsulation of HRP in Ac-DEX reduces its storage temperature dependence and enhances its stability outside cold chain conditions. Homogenized particles performed better than probe sonicated particles and retained 70%of the enzyme's initial activity as compared to free HRP that retained only 40%of the initial activity after 3 months of storage at 25 掳C or 45 掳C. Additionally, HRP activity was more stable when encapsulated in Ac-DEX, and the variance in enzyme activity between the different storage temperatures was not observed for either particle preparation. This suggests that storage at a constant temperature is not required with vaccines encapsulated in Ac-DEX particles. Overall, our results suggest that an Ac-DEX based micro-/nanoparticles system has wide applications as vaccines and drug delivery carriers, including those in developing nations.