Cyclodextrin-based sustained and controllable release system of insulin utilizing the combination system of self-assembly PEGylation and polypseudorotaxane formation.
Sustained and controllable release of insulin is strongly required to achieve the ideal treatment of diabetes. We previously developed "self-assembly PEGylation retaining activity (SPRA) technology" via a host-guest interaction between PEGylated β-cyclodextrin and adamantane-appended insulin, and resulting PEGylated insulin was termed SPRA-insulin. So far, we also demonstrated that covalently PEGylated insulin forms polypseudorotaxanes (PPRXs) with cyclodextrins (PPRX technology). In the present study, we designed and evaluated the combination system of SPRA technology and PPRX technology to achieve a sustained and controllable release system of insulin. SPRA-insulin formed PPRXs with α-cyclodextrin and γ-cyclodextrin. In addition, SPRA-insulin/cyclodextrin PPRXs provided sustained and controllable release of insulin beyond the each single technology both in vitro and in vivo. These results suggest that the combination system of SPRA technology and PPRX technology is useful for design of a sustained and controllable release system of insulin.
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Tatsunori
T
Hirotsu
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Taishi
T
Higashi
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Keiichi
K
Motoyama
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: arimah@gpo.kumamoto-u.ac.jp.
Hidetoshi
H
Arima
D000818:Animals; D003505:Cyclodextrins / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D017208:Rats, Wistar; D043862:Rotaxanes / Q000737:chemistry*
D003505:Cyclodextrins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007328:Insulin; D043862:Rotaxanes; D011092:Polyethylene Glycols
Adamantane; Controllable release; Cyclodextrin; Insulin; Polyethylene glycol; Polypseudorotaxane