title: Enhanced stability of horseradish peroxidase encapsulated in acetalated dextran microparticles stored outside cold chain conditions.
abstract: 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 (-20 °C, 4 °C, 25 °C or 45 °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 °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 °C or 45 °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.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kanthamneni
authors.forename: Sadhana
authors.initials: S
authors.lastname: Sharma
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Meenach
authors.forename: Beau
authors.initials: B
authors.lastname: Billet
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Zhao
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers; D004355:Drug Stability; D004356:Drug Storage; D006735:Horseradish Peroxidase / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D013696:Temperature; D014612:Vaccines / Q000737:chemistry*
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D014612:Vaccines; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase