Autor(es)Kramer Ryan M, Zeng Yuhong, Sahni Neha, Kueltzo Lisa A, Schwartz Richard M, Srivastava Indresh K, Crane Lindsey, Joshi Sangeeta B, Volkin David B, Middaugh C Russell

ResumoChikungunya virus (CHIKV) is an alphavirus that infects millions of people every year, especially in the developing world. The selective expression of recombinant CHIKV capsid - envelope proteins results in the formation of self-assembled virus-like particles (VLPs) that have been shown to protect nonhuman primates against infection from multiple strains of CHIKV. This study describes the characterization, excipient screening, - optimization of CHIKV VLP solution conditions toward the development of a stable parenteral formulation. The CHIKV VLPs were found to be poorly soluble at pH 6 - below. Circular dichroism, intrinsic fluorescence, - static - dynamic light scattering measurements were therefore performed at neutral pH, - results consistent with the formation of molten globule structures were observed at elevated temperatures. A library of generally recognized as safe excipients was screened for their ability to physically stabilize CHIKV VLPs using a high-throughput turbidity-based assay. Sugars, sugar alcohols, - polyanions were identified as potential stabilizers - the concentrations - combinations of select excipients were optimized. The effects of polyanions were further studied, - while all polyanions tested stabilized CHIKV VLPs against aggregation, the effects of polyanions on conformational stability varied.

Palavras-ChaveParticle size; Physical stability; Physicochemical properties; Preformulation; Protein formulation; Spectroscopy; Stabilization; Thermal analysis; Vaccines

ImprentaJournal of Pharmaceutical Sciences, v. 102, n. 12, p. 4305-4314, 2013

DescritoresChikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever

Data de Publicação:2013