Synthesis, Characterization and Biocompatibility of N-palmitoyl L-alanine-based Organogels as Sustained Implants of Granisetron and Evaluation of thier Antiemetic Effect.

OBJECTIVE

To assess the gelation power of N-palmitoyl L-alanine derivatives in injectable oils and to use the best chosen organogel as parenteral implant of granisetron for the treatment of emesis.

METHODS

Twelve N-palmitoyl L-alanine derived organogels were developed and evaluated in terms of morphology, thermal properties and in vivo performance. The ability of the selected formula to form in situ gel upon subcutaneous injection in rats and its biocompatibility were monitored over 2 weeks by histopathological examination of the injection site.

RESULTS

The acid derivative (N-palmitoyl L-alanine; PA) was superior to ester derivatives. The chosen formula (PA/safflower oil 10% w/v) was successful in forming an in situ gel of granisetron when subcutaneously injected in rats, lasting for 2 weeks and proved to be biocompatible by histopathological examination. Moreover, it exerted an extended antiemetic activity by decreasing the cisplatin-induced pica for a duration of 96 h and reduced preprotachykinin A mRNA expression and Substance P level for up to 4 days (gastric tissue) or 5 days (medulla oblongata) in rats.

CONCLUSIONS

Granisetron organogel could be considered as a safe, sustained-release and supportive anticancer treatment in both acute and chronic emesis as well as an accompanying treatment with chemotherapeutics in cancer cases.