Ring-opening polymerization of ε-caprolactone initiated by ganciclovir (GCV) for the preparation of GCV-tagged polymeric micelles

• Published in: Molecules (Basel, Switzerland) Vol. 20; no. 2; pp. 2857 - 2867
• Main Authors: Sawdon, Alicia J, Peng, Ching-An
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 10.02.2015; MDPI AG
• Subjects: Antiviral Agents - chemistry; Caproates - chemistry; Cell Proliferation - drug effects; chitosan; Chitosan - chemistry; Copolymers; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug delivery systems; ganciclovir; Ganciclovir - chemistry; Ganciclovir - pharmacology; Graft copolymers; HT29 Cells; Humans; Lactones - chemistry; Micelles; Nanoconjugates - chemistry; Nanoparticles; Nucleosides; Particle Size; poly(caprolactone); Polymerization; ring-opening polymerization; Synthesis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules20022857

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.