Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation
Abstract
Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery. An organogel system based on l-lysine derivatives was designed and prepared to induce a thermal sensitive implant with higher transition temperature, better mechanical strength, and shorter gelation time. The organogel was prepared by injectable soybean oil and methyl (S)-2,5-ditetradecanamidopentanoate (MDP), which was synthesized for the first time. Candesartan cilexetil (CC) was chosen as model drug. Different formulations were designed and optimized by response surface method. Thermal, rheology properties, and gelation kinetics of the optimized formulation had been characterized. The release behaviors in vitro, as well as in vivo were evaluated in comparison with the oily solution of drugs. Finally, the local inflammation response of in situ organogel was assessed by histological analysis. Results showed that the synthesized gelator, MDP, had a good gelation ability and the organogels obtained via the self-assembly of gelators in vegetable oils exhibited great thermal and rheology properties, which guaranteed their state in body. In vivo pharmacokinetic demonstrated that the organogel formulation could extend the drug release and ...Continue Reading
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