Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

Abstract

SummaryCyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products.

Cyclodextrin-Based Molecular Accessories for Drug Discovery and Drug Delivery

“…High-molecular weight PEGs (>2000 Da) form polypseudorotaxane hydrogels, not precipitates, with α-and γ-CyDs, because the polypseudorotaxane moiety works as crosslinking points. 24,25) Therefore we prepared polypseudorotaxane hydrogels containing insulin and lysozyme, relatively low-molecular weight proteins, and evaluated their utility as sustained release carriers 26,27) (Fig. 4e).…”

Supramolecular Pharmaceutical Sciences: A Novel Concept Combining Pharmaceutical Sciences and Supramolecular Chemistry with a Focus on Cyclodextrin-Based Supermolecules

“…To the best of our knowledge, this is the first report on the successful sustained drug release system based on polyrotaxane or polypseudorotaxane in vivo. This technology is also applicable for PEGylated liposome 159) ( Fig. 6e), PEGylated gene and siRNA carriers [160][161][162] (Fig.…”