Preparation of a liposomal delivery system and its in vitro release of rapamycin.

Zhi-Lin Miao,Xu-Bin Suo,Na Duan,Li Wang,Hong-Yang Du,Ying-Jie Deng,Li-Jie Cui,Xiao-Yu Wang,Xiao Wang

doi:10.3892/etm.2015.2201

Abstract

The aim of this study was to prepare a liposomal delivery system for rapamycin and study its in vitro release characteristics. The results may provide a foundation for the further development of a liposomal delivery system for rapamycin and the establishment of a new active treatment method targeted towards the cellular components of atherosclerotic plaques. The ethanol injection method was used to prepare rapamycin-containing liposomes. The formulation was optimized by orthogonal design, and the degree of rapamycin release by the liposomes was measured by the reverse dialysis method. Orthogonal testing showed that the optimum formulation had a phospholipid concentration of 4%, a phospholipid-cholesterol mass ratio of 8:1, a drug-lipid mass ratio of 1:20 and an aqueous phase pH of 7.4. Rapamycin-containing liposomes with an encapsulation efficiency of 82.11±2.13% were prepared, and the in vitro release of rapamycin from the liposomes complied with a first-order kinetic equation. In conclusion, the formulation was optimized, the prepared liposomes had a high rapamycin encapsulation rate and good reproducibility, and their in vitro release had a certain delayed-release effect.

Highlights

Cardiovascular disease is a major disease that threatens human health, with the main pathological feature being atherosclerosis (AS)
The results of orthogonal experiments were analyzed by multivariate analysis of variance (MANOVA), while partial results were analyzed by ANOVA
Excessively high phospholipid concentrations resulted in the aggregation of phospholipids, making it difficult for the rapamycin to be released

Summary

Introduction

Cardiovascular disease is a major disease that threatens human health, with the main pathological feature being atherosclerosis (AS). There is currently no effective preventive measure for diseases with intimal plaque hyperplasia as the main pathological feature; in particular, there is no drug that directly targets the molecular components of blood‐intimal atherosclerotic plaques. While a drug‐coated stent is effective in the focal vessel, it is not able to act at non‐stent covered sites or in other systemic diseases, such as AS, which cannot be treated with a stent [4]. Rapamycin is a drug with poor solubility that is unstable in stomach acid, and has an oral bioavailability of only 14%. It cannot play a systemic role through oral or intravenous administration methods [5]

Objectives

Methods

Results