Controlled release of a model hydrophilic high molecular weight compound from injectable non-lamellar liquid crystal formulations containing different types of phospholipids.

Abstract

Skin offers an easily accessible and convenient site for the administration of drugs. Therefore, the development of injectable formulations with controlled drug release properties are now expected to deliver middle- and large-size biomolecules. In the present study, formulations mainly composed of a novel polyol ester with an isoprenoid side chain; mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE), that was capable of forming a non-lamellar liquid crystal (NLLC), were prepared with different types of phospholipid. Then, factors that affected the release of a model entrapped drug, fluorescein-isothiocyanate dextran (FD-4, M.W. 4,000), from the MGE formulations were analyzed with multi-regression analysis. In addition, self-assembly of the NLLC structure was investigated using small-angle X-ray scattering analysis after contacting the MGE formulations with water. NLLC-forming ability of the formulations after s.c. injection into rats was also confirmed using microscopic observations. FD-4 concentrations in blood were determined after s.c. injection of the MGE formulations. The injectable MGE formulations successfully constructed NLLC structures to form a sponge-like gel after contact with water in vitro and in vivo (in rats) as well. In in vitro conditions, the amount of FD-4 released from the formulations was altered by changing the type and concentration of phospholipid in the MGE formulations and can be expressed with parameters such as MGE content and interplanar spacing of the NLLC. A significantly sustained FD-4 level in the blood was observed after s.c. injection of the formulations. These results suggested that injectable MGE formulations may have the potential to achieve controlled release profiles of drugs after s.c. injection.