The Effect of Different Lipid Components on the in Vitro Stability and Release Kinetics of Liposome Formulations

Abstract

Liposomes are colloidal carriers that form when certain (phospho)lipid molecules are hydrated in an aqueous media with some energy input. The ideal liposome formulation with optimum stability will improve drug delivery by decreasing the required dose and increasing the efficacy of the entrapped drug at the target organ or tissue. The most important parameter of interest in this article was to compare the efficacy of three different liposomes formulated with DSPC, DMPC, and DPPC, all saturated neutral phospholipids with different acyl chain lengths and transition temperatures. DMPC has a phase transition temperature (Tc) below 37°C, whereas the other two phospholipids possess Tcs above the physiological temperature. These lipids were then added to a cholesterol concentration of 21% to optimize the stability of the vesicles. The liposomes were prepared by a sonication and incubated in phosphate buffered saline (PBS) at 4°C and 37°C. The encapsulation efficiency, initial size, and drug retention of the vesicles were tested over a 48-hr period employing radiolabeled inulin as a model drug. The phase transition temperature of liposomes, which depends on the Tc of the constituent lipids, was an important factor in liposome stability. Of all the liposomes tested, the greatest encapsulation efficiency was found for the DSPC liposomes (2.95%) that also had the greatest drug retention over 48 hr at both 4°C (87.1 ± 6.8%) and 37°C (85.2 ± 10.1%), none of these values being significantly different from time zero. The lowest drug retention was found for DMPC liposomes for which a significant difference in drug retention was seen after only 15 min at both 4°C (47.3 ± 6.9%) and 37°C (53.8 ± 4.3%). The DPPC liposomes showed a significant difference in drug retention after 3 hr at 4°C (62.1 ± 8.2%) and after 24 hr at 37°C (60.8 ± 8.9%). Following the initial drop at certain time intervals a plateau was reached for all of the liposome formulations after which no significant difference in drug retention was observed. In conclusion, liposomes with higher transition temperatures appear to be more stable in PBS either at 4°C or 37°C, indicating that the increase in acyl chain length (and therefore transition temperature) is directly proportional to stability.