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

• Published in: Asian journal of pharmceutical sciences Vol. 18; no. 5; p. 100848
• Main Authors: Cui, Zhixiang, Cui, Shuman, Qin, Lu, An, Yalin, Zhang, Xin, Guan, Jian, Wong, Tin Wui, Mao, Shirui
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2023; School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China%Particle Design Research Group,Faculty of Pharmacy,Universiti Teknologi MARA Selangor,Puncak Alam 42300,Malaysia; Non-Destructive Biomedical and Pharmaceutical Research Centre,Smart Manufacturing Research Institute,Universiti Teknologi MARA Selangor,Puncak Alam 42300,Malaysia; Shenyang Pharmaceutical University; Elsevier
• Subjects: Muco-penetrating; Mucus; Nanoparticles; Oral insulin; Original Research Paper; Streptavidin; Virus-mimicking; Nanoparticles; Oral insulin; Muco-penetrating; Mucus; Virus-mimicking; Streptavidin
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2023.100848

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. [Display omitted]