The influence of lipid composition and surface charge on biodistribution of intact liposomes releasing from hydrogel-embedded vesicles.

Mixed drug delivery systems possess advantages over discrete systems, and can be used as a strategy to design more effective formulations. They are more valuable if the embedded particles perform well, rather than using drugs that have been affected by the surrounding vehicle. In order to address this concept, different liposomes have been incorporated into hydrogel to evaluate the potential effect on the controlled release of liposomes. Radiolabeled liposomes, with respect to different acyl chain lengths (DMPC, DPPC, or DSPC) and charges (neutral, negative [DSPG], or positive [DOTAP]) were integrated into chitosan-glycerophosphate. The results obtained from the biodistribution showed that the DSPC liposomes had the highest area under the curve (AUC) values, both in the blood (206.5%ID/gh(-1)) and peritoneum (622.3%ID/gh(-1)), when compared to the DPPC and DMPC formulations, whether in liposomal hydrogel or dispersion. Interesting results were observed in that the hydrogel could reverse the peritoneal retention of negatively charged liposomes, increasing to 8 times its AUC value, to attain the highest amount among all formulations. The interactions between the liposomes and chitosan-glycerophosphate, confirmed by the Fourier transform infrared (FTIR) spectra as shifted characteristic peaks, were observed in the combined systems. Overall, the hydrogel could control the release of intact liposomes, which could be manipulated by both the liposome type and interactions between the two vehicles.

Hydrogel-embeded vesicles, as a novel approach for prolonged release and delivery of liposome, in vitro and in vivo.

A novel delivery concept based on the integration of liposomes in hydrogel for the controlled release of liposomes was developed. As an in situ forming hydrogel, chitosan-glycerophosphate was used and gelation time at different temperatures was studied. Liposomes (DSPC/chol/DOPE) were labelled with (99m)Tc-hexamethylpropyleneamineoxime ((99m)Tc-HMPAO). (99m)Tc-HMPAO solution, hydrogel/(99m)Tc-HMPAO, (99m)Tc-HMPAO liposomes and hydrogel/(99m)Tc-HMPAO liposomes were injected into mouse peritoneum. The percentages of radioactive injected dose per gram of tissue (%ID/g) and %ID of peritoneum lavage were obtained. Results showed that free label left the peritoneal cavity rapidly in both solution and hydrogel forms, such that the activity was 2.5 and 3.8 (%ID) after one hour, respectively. The values for liposomes and liposomal hydrogel were 25.8 and 51.2 (%ID) and decreased to 1.9 and 19.2 after 24 h, respectively. The blood profile of liposomal hydrogel showed a two-phase profile including a descending trend in early hours regarding gel formation followed by an ascending trend due to gel disappearance by time. Free label had high activity in reticuloendothelial system (RES) and the gastrointestinal tract during the early hours and then dropped. In contrast, the accumulation of liposomes increased in RES during 24 h in the range of 1-34.5 and 1.1-35.1 (%ID/g) for plain liposomes and liposomal hydrogel, respectively. Overall, incorporation of liposomes in hydrogel could be a useful strategy to prolong the release of liposomes.