Studies on acyclovir-dextran conjugate: synthesis and pharmacokinetics

Area of Science:

• Pharmacology
• Drug Delivery
• Hepatitis Research

Background:

• Acyclovir exhibits in vitro activity against hepatitis B virus (HBV).
• Limited clinical use of acyclovir for HBV is due to poor solubility and low liver distribution.
• Novel drug delivery systems are needed to enhance acyclovir's efficacy.

Purpose of the Study:

• To synthesize an acyclovir-dextran conjugate to improve solubility and liver targeting.
• To evaluate the in vitro release kinetics of acyclovir from the conjugate.
• To assess the in vivo pharmacokinetics and liver distribution of the conjugate in mice.

Main Methods:

• Acyclovir-dextran conjugate synthesized via Schiff's base formation.
• Solubility testing compared conjugate to free acyclovir.
• In vitro drug release studies conducted in phosphate-buffered saline (PBS) at pH 7.4 and 37°C.
• Intravenous (i.v.) administration of acyclovir and conjugate in mice.
• Pharmacokinetic analysis using High-Performance Liquid Chromatography (HPLC) to measure drug concentrations in plasma, liver, and kidney.

Main Results:

• Acyclovir-dextran conjugate demonstrated a 12-fold increase in solubility compared to free acyclovir.
• Slow release of acyclovir from the conjugate observed with a rate constant of 0.0035 hr⁻¹ at physiological conditions.
• Significantly higher acyclovir distribution in the liver following i.v. administration of the conjugate compared to free acyclovir.
• HPLC analysis confirmed drug concentrations in key organs.

Conclusions:

• Acyclovir-dextran conjugate effectively enhances acyclovir solubility and liver targeting.
• The conjugate exhibits favorable in vitro release characteristics and improved in vivo liver distribution.
• Acyclovir-dextran conjugate represents a promising drug candidate for hepatitis B treatment.