Self-assembled L-alanine derivative organogel as in situ drug delivery implant: characterization, biodegradability, and biocompatibility.
OBJECTIVE
The purpose of this work is to prepare and characterize the novel in situ forming implants, obtained through self-assembling of N-stearoyl-L-alanine methyl ester (SAM) in pharmaceutical oils, and to evaluate the biodegradability and biocompatibility of this organogel system.


METHODS
Minimum gelation concentration was used to measure the gelling ability of gelator SAM in different oils to select the optimal oil for further research. Phase transition temperatures of SAM/soybean oil organogels were determined by differential scanning calorimetry. Comparative studies on the in vitro degradation and in vivo degradation of SAM/soybean oil organogels in mice were investigated. Cytotoxicity tests and histological analysis of SAM/soybean oil organogels were studied by using mouse fibrosarcoma cells and mouse, respectively.


RESULTS
As an organogelator, SAM could gel a variety of oils at different minimum gelation concentration. Among them, it had the best-gelling ability in soybean oil, and the SAM/soybean oil organogel could be turned into gels abruptly at body temperature when the concentration of SAM was higher than 5% (w/v) to be used as an injectable system. The in vitro degradation rate of organogel was inversely proportional to the organogelator concentration, whereas the degradation rate in vivo was much higher than in vitro, and gels were almost disappeared after 6 weeks. The selected formulation showed excellent biocompatibility as tested by in vitro cytotoxicity and in vivo histological evaluation.


CONCLUSIONS
SAM/soybean oil organogel has excellent biodegradability and biocompatibility, which indicates that it has a great potential for safe in situ forming drug delivery.
School of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, PR China.
Keke
K
Wang
Qiang
Q
Jia
Fei
F
Han
Hongzhuo
H
Liu
Sanming
S
Li
D000818:Animals; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004343:Drug Implants; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005782:Gels; D007279:Injections, Subcutaneous; D055666:Lipopeptides / Q000737:chemistry* / Q000633:toxicity; D008297:Male; D008422:Materials Testing; D051379:Mice; D044367:Phase Transition; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry; D040521:Subcutaneous Tissue; D044366:Transition Temperature
D001672:Biocompatible Materials; D004337:Drug Carriers; D004343:Drug Implants; D005782:Gels; D055666:Lipopeptides; D013024:Soybean Oil