Nanocapsules of therapeutic proteins with enhanced stability and long blood circulation for hyperuricemia management

• Published in: Journal of controlled release 2017-06, Vol.255, p.54-61
• Main Authors: Zhang, Xiaopei, Xu, Duo, Jin, Xin, Liu, Gan, Liang, Sheng, Wang, Hui, Chen, Wei, Zhu, Xinyuan, Lu, Yunfeng
• Format: Article
• Language: English
• Subjects: Animals; Cell Line; Cell Proliferation - drug effects; Drug Stability; Endocytosis; HeLa Cells; Humans; Hyperuricemia - blood; Hyperuricemia - drug therapy; Hyperuricemia - metabolism; Hyperuricemia management; Immunoglobulin E - blood; Immunoglobulin G - blood; Immunoglobulin M - blood; Long circulation; Male; Mice, Inbred BALB C; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanocapsules - therapeutic use; Protein delivery; Protein therapeutics; Pyrrolidinones - administration & dosage; Pyrrolidinones - chemistry; Pyrrolidinones - pharmacokinetics; Pyrrolidinones - therapeutic use; Tissue Distribution; Trypsin - chemistry; Urate Oxidase - administration & dosage; Urate Oxidase - chemistry; Urate Oxidase - pharmacokinetics; Urate Oxidase - therapeutic use
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.03.019

Among a broad spectrum of medical treatments, protein therapeutics holds tremendous opportunities for the treatment of metabolic disorders, cancer, autoimmune diseases and etc. Broad adaption of protein therapeutics, however, still remain challenging, not only because of poor protein stability, but they also experience fast clearance after administrated and elicit immune responses, resulting in undesirable biodistribution and short blood residence time. In this study, we demonstrate a novel protein delivery method via encapsulating therapeutic proteins within thin shells of poly(N-vinylpyrrolidone) (PVP), which leads to significantly improved protein stability, reduced macrophage uptake, prolonged circulation time and reduced immunogenicity. Exemplified with urate oxidase (UOx), the enzyme used for hyperuricemia treatment, as-formed UOx nanocapsules, n(UOx), exhibits enhanced stability, more significant therapeutic effects, and a more than 10-fold improvement in circulation time when compared with native UOx. This technology not only demonstrates the use of UOx nanocapsules for hyperuricemia management, but also provides a general approach for a broad spectrum of therapeutic proteins for in vivo applications. [Display omitted]