Comparison of virus-capsid mimicking biologic-shell based versus polymeric-shell nanoparticles for enhanced oral insulin delivery

• Published in: Asian Journal of Pharmaceutical Sciences
• Main Author: Cui Z.; Cui S.; Qin L.; An Y.; Zhang X.; Guan J.; Wong T.W.; Mao S.
• Format: Article
• Language: English
• Published: Shenyang Pharmaceutical University 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85174340867&doi=10.1016%2fj.ajps.2023.100848&partnerID=40&md5=27544a19518ed81bcc0dcdf0965238e3

Virus-capsid mimicking mucus-permeable nanoparticles are promising oral insulin carriers which surmount intestinal mucus barrier. However, the impact of different virus-capsid mimicking structure remains unexplored. In this study, utilizing biotin grafted chitosan as the main skeleton, virus-mimicking nanoparticles endowed with biologic-shell (streptavidin coverage) and polymeric-shell (hyaluronic acid/alginate coating) were designed with insulin as a model drug by self-assembly processes. It was demonstrated that biologic-shell mimicking nanoparticles exhibited a higher intestinal trans-mucus (>80%, 10 min) and transmucosal penetration efficiency (1.6–2.2-fold improvement) than polymeric-shell counterparts. Uptake mechanism studies revealed caveolae-mediated endocytosis was responsible for the absorption of biologic-shell mimicking nanoparticles whereas polymeric-shell mimicking nanoparticles were characterized by clathrin-mediated pathway with anticipated lysosomal insulin digestion. Further, in vivo hypoglycemic study indicated that the improved effect of regulating blood sugar levels was virus-capsid structure dependent out of which biologic-shell mimicking nanoparticles presented the best performance (5.1%). Although the findings of this study are encouraging, much more work is required to meet the standards of clinical translation. Taken together, we highlight the external structural dependence of virus-capsid mimicking nanoparticles on the muco-penetrating and uptake mechanism of enterocytes that in turn affecting their in vivo absorption, which should be pondered when engineering virus-mimicking nanoparticles for oral insulin delivery. © 2023