title: Ring-opening polymerization of ε-caprolactone initiated by ganciclovir (GCV) for the preparation of GCV-tagged polymeric micelles.
abstract: Ganciclovir (GCV) is a nucleoside analogue with antiviral activity against herpes viral infections, and the most widely used antiviral to treat cytomegalovirus infections. However, the low bioavailability and short half-life of GCV necessitate the development of a carrier for sustained delivery. In this study, guanosine-based GCV was used as the initiator directly in ring-opening polymerization of ε-caprolactone (ε-CL) to form hydrophobic GCV-poly(caprolactone) (GCV-PCL) which was then grafted with hydrophilic chitosan to form amphiphilic copolymers for the preparation of stable micellar nanoparticles. Successful synthesis of GCV-PCL and GCV-PCL-chitosan were verified by 1H-NMR analysis. Self-assembled micellar nanoparticles were characterized by dynamic light scattering and zetasizer with an average size of 117 nm and a positive charge of 24.2 mV. The drug release kinetics of GCV was investigated and cytotoxicity assay demonstrated that GCV-tagged polymeric micelles were non-toxic. Our results showed that GCV could be used directly in the initiation of ring-opening polymerization of ε-CL and non-toxic polymeric micelles for GCV delivery can be formed.
authors: Department of Chemical Engineering, Michigan Technological University, Houghton, MI 49931, USA. ajsawdon@mtu.edu.
authors: Alicia J
authors: AJ
authors: Sawdon
authors: Department of Chemical Engineering, Michigan Technological University, Houghton, MI 49931, USA. cpeng@mtu.edu.
authors: Ching-An
authors: CA
authors: Peng
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry; D002208:Caproates / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015774:Ganciclovir / Q000737:chemistry* / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008823:Micelles; D058726:Nanoconjugates / Q000737:chemistry*; D010316:Particle Size
chemical_list: D000998:Antiviral Agents; D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; D008823:Micelles; D058726:Nanoconjugates; C121056:caprolactone; D048271:Chitosan; D015774:Ganciclovir