Vesicular phospholipid gels using low concentrations of phospholipids for the sustained release of thymopentin: pharmacokinetics and pharmacodynamics.

Abstract

Vesicular phospholipid gels (VPGs) with high concentrations of phospholipids are used as implantable depots for sustained release of drugs due to high viscosity. This study aimed to investigate VPGs with low concentrations of phospholipids for subcutaneous injection and sustained release in vivo. A small peptide, thymopentin, was selected and incorporated into various VPG formulations. The VPG viscosity was greatly increased with higher concentrations of phospholipids (E80) and thus VPGs based on low lipid contents are more suitable for injection. Additionally, VPGs loaded with 5-hydroxy-fluorescein-thymopetin (5-FAM-TP5-VPGs) were developed and their pharmacokinetic profile was investigated in vivo. After subcutaneous injection, the release time of 5-FAM-TP5 was 216 h for 5-FAM-TP5-VPGs (containing 300 mg/g lipid), which was much longer than that of 5-FAM-TP5 solution. The therapeutic efficacy of TP5-VPGs (containing 300 mg/g lipid) after subcutaneous administration once a week was demonstrated to be comparable to that of TP5 solution injected subcutaneously once daily for 7 days. In conclusion, TP5-VPGs with low lipid content (300 mg/g) displayed sustained release properties in vivo that may serve as a sustained delivery system for subcutaneous injection.