Self-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation

Abstract

(2016) Self-assembled drug delivery system based on low-molecular-weight bisamide organogelator: synthesis, properties and invivo evaluation, Drug Delivery, 23:8, 3168-3178, DOI: 10.3109/10717544.2016 RESEARCH ARTICLESelf-assembled drug delivery system based on low-molecular-weight bis-amide organogelator: synthesis, properties and in vivo evaluation Zhen Li, Jinxu Cao, Heran Li, Hongzhuo Liu, Fei Han, Zhenyun Liu, Chao Tong, and Sanming Li School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning, P.R. China Abstract Context: Orgnaogels based on amino acid derivatives have been widely used in the area of drug delivery. Objective: 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. Materials and methods: 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 and discussion: 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 maintain a therapeutically effective plasma concentration at least 10 d. In addition, this implant showed acceptable moderate inflammation. Conclusion: The in situ forming L-lysine-derivative-based organogel could be a promising matrix for sustained drug delivery of the drugs with low solubility. KeywordsBiocompatibility, gelator, in situ implant system, in vivo release, organogel History

Conventional and Unconventional Crystallization Mechanisms

“…Through manipulation of nucleation and growth, ultrasounds can potentially provide improved control for the assembly of crystal structures in foods to control texture or improve separation [8]. It is believed that these ultrasonic effects are superior to conventional agitation to control and stimulate the reaction rate, supersaturation level, nucleation, and crystal growth [22].…”

“…The formation of these structures through supramolecular assembly is of great interest, since they can form semisolid phases that are produced at low cost [32]. Several researchers have focused their studies on the properties of structurants to form organogels [22,[36][37][38].…”

Hansen Solubility Parameters as a Tool in the Quest for New Edible Oleogels

“…By understanding the Hansen space for molecules that gel vegetable oil, it will provide a targeted approach to identify new food‐grade gelators. In an attempt to observe if there is a region in Hansen space that is concentrated in oleogelators, a meta‐analysis was performed and 34 reported molecular gels that gelled vegetable oil were identified (Table ) (Bastiat & Leroux, ; Behera, Patil, Sargiri, Pal, & Ray, ; Feng, Chen, Cai, Wen, & Liu, ; Hanabusa, Hiratsuka, Kimura, & Shirai, ; Hanabusa, Inoue, Suzuki, Kimura, & Shirai, ; Hanabusa, Kawakami, Kimura, & Shirai, ; Hanabusa, Tanaka, Suzuki, Kimura, & Shirai, ; Hishikawa, Sada, Watanabe, Miyata, & Hanabusa, ; Li et al, ; Motulsky et al, ; Rao, Kamalraj, Swain, & Mishra, ; Rogers, Wright, & Marangoni, ; Suzuki, Uematsu, & Hanabusa, ; Suzuki, Yumoto, Shirai, & Hanabusa, ; Yu et al, , ). The benefit to preforming this type of analysis was it allows nonfood‐grade gelators to be used to identify the HSP of molecules that are able to vegetable oil.…”

“…HSP's frequency of occurrence of reported molecular gelators that gel vegetable oil. Data were obtained for n = 34 unique molecular gelators (Bastiat & Leroux, ; Feng et al, ; Hanabusa, Hiratsuka, et al, ; Hanabusa, Inoue, et al, ; Hanabusa, Kawakami, et al, ; Hanabusa, Tanaka, et al, ; Hishikawa et al, ; Li et al, ; Motulsky et al, ; Rao et al, ; Suzuki et al, , ; Yu et al, , )…”

Organogels based on amino acid derivatives and their optimization for drug release using response surface methodology

“…In our previous work, a series of amino acid based gelators were synthesized to explore the role of the gelator structure on functional properties, and found that the in situ organogel-forming implant has excellent biodegradability and biocompatibility, which indicates great potential for safe in situ forming drug delivery [29][30][31][32]. However, it is still questionable how the burst release could be modified through the formulation composition.…”