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 Tc-99m-hexamethylpropyleneamineoxime (Tc-99m-HMPAO). Tc-99m-HMPAO solution, hydrogel/Tc-99m-HMPAO, Tc-99m-HMPAO liposomes and hydrogel/Tc-99m-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.