Synthesis and anti-hepatitis B virus activity of acyclovir conjugated stearic acid-g-chitosan oligosaccharide micelle

The controlled release of chemotherapeutical reagent with high water solubility was a challenge for targeting drug delivery. In this article, an antiviral agent, acyclovir was conjugated to chitosan-g-stearate via a succinate linker. Chitosan-g-stearate was synthesized by the reaction between the amino group of chitosan oligosaccharide and the carboxyl group of stearic acid. Both chitosan-g-stearate and acyclovir-chitosan-g-stearate could self aggregate to form micelles in aqueous solution. Acyclovir-chitosan-g-stearate micelle had smaller size (24.9 +/- 1.1 nm), lower positive zeta potential (24.4 mV) and higher critical micelle concentration (123.23 mg mL(-1)) in distilled water, compared with those of chitosan-g-stearate (34.2 +/- 3.8 nm, 46.9 +/- 6.2 mV and 90.07 mg mL(-1), respectively). Acyclovir release from acyclovir-chitosan-g-stearate micelles could prolong to 24h in vitro. For the free acyclovir and acyclovir-chitosan-g-stearate micelle with acyclovir concentration of 0.044 mu M mL(-1), the inhibition of acyclovir on hepatitis B surface antigen was increased from 12.7% to 22.3% from 5 d to 9 d, while the inhibition of acyclovir-chitosan-g-stearate was increased from 58.2% to 80.3% from 5 d to 9 d. The cellular uptake and antiviral activity of acyclovir was successfully increased and improved through chemical conjugation of acyclovir to chitosan-g-stearate. (C) 2010 Elsevier Ltd. All rights reserved.