Study Of Amino Acid Derivatives Organogel For Sustained Drug Delivery System

This paper aim at studying sustain propertied of amino acid derivatives organogel in oral drug delivery system and parenteral delivery system. Biodegradable amino acid derivatives'gelators were sythensized and organogel was prepared. Its properties were determined, in order to expect to provide theory support for the research of develop sustained organogel by extending the drug release time, avoiding peak and valley phenomenon, and reducing drug adverse reaction.Using "amino acids nucleophilic substitution method" , L-alanine, L-lysine and L-phenylalanine as parent to carry out amide reaction with lauroyl chloride, so six gel factor LAM, LLM, LPM, LAA, LLA, and LPA were synthesized. Seven medicinal oil phases were used to prepared organic gel, respectively. Then discuss the mechanism of gelling and inspect the influence of the molecular structure of gel factor on gel properties. The results showed that the driving force in forming the organogel is the hydrogen bond between the intermolecular. The structure of the gelator has significant effect on the mechanics,thermodynamics, degradation properties of the organogel system. The gel without or with too much hydrogen bond donors in the molecular structure can not form gels.In order to discuss the feasibility of organic gel as oral slow-release drug delivery system,the mechanics, thermodynamic properties of blank amino acid derivatives organic gel were first studied. The flow method was used to determine the phase transition temperature of organic gel, it is shown that different gelators and the proportion of gelators are related to the phase transition temperature, the controllability of Tgs can be achieved by the adjustment between the structure and the concentration of gelators, so as to achieve the organic gel systems with stable thermodynamic properties which was expected.The rheological experimental results showed that the rheological curve of organic situ gel have constant elastic modulus (G'), viscous modulus (G") and low Angle, and present the frequency dependence. And the rheological parameters of this system showed obvious structure and concentration dependence of gelators, and the drug delivery system with appropriate viscosity and mechanical strength can be achieved by regulating the structure and consumption of gelators.The difficult capacitive model drug nimodipine (NM) were added into the gel, then study the in vivo and in vitro release behavior and explore the nature of the sustained-release drug delivery and release law of organogel. The results show that the NM can directly dissolve in the oil phase. The in vitro release mechanism is closely associated with the gelator structure and concentration: the differences of the structure and concentration of gelator, resulting in the differences of drug release rate and release mechanism. Compared to the NM aqueous suspension, MRT,t1/2, Tmax of the NM-OG significantly increases,indicating that the NM organic gel to improve the drug in the body burst release, with significant sustained drug release capabilities. Compared with the control group, NM organic gel can significantly improve the drug's relative bioavailability.Select polypeptides of thymopentin (TPS) as a model drug to study the feasibility of the organic gel system as the carrier of the protein polypeptides. The TPS is made of W / O microemulsion and added into the organogel, the system has good stability. The organic gel system which contains TPS has low release rate in vitro, and 10 hours of the release of 90%.Pharmacodynamic experiments showed that the preparation of oral TPS organic gel formulations have a significant enhancement to the non-specific immune function, specific cellular immunity and humoral immunity of the immunocompromised mice, the same with injectable formulations pharmacodynamic results. This proved that organic situ gel contained the capabilities of drug-loaded and controlled drug release.In order to explore the feasibility of organicgel as the nonoral sustained-release drug delivery systems, the degradation and biocompatibility of the system were studied. The results show that both LAM-OG and the LLM-OG system degradated slowly in vitro and in vivo, but due to the in the presence of enzymes, in vivo degradation was significantly faster than in vitro degradation. Subcutaneous injection of the organic gel tissue sections showed that there is no acute inflammatory response in the early injection, and showed a lower inflammatory response in 4-8 weeks healing process, suggesting that such in situ gel system has good in vivo biocompatibility.To explore the release law of the in situ gel, poorly soluble model drug estradiol (E2)were add into the gel, and in vivo and in vitro release behavior were carried out, The results showed that E2-IOG has significant in vitro sustained release effect, which may provide cumulative sustained release to release the drug up to 30 days. Gelator structure and concentration affect the E2 release rate and release form. Compared to the E2 oil solution, in vivo role of time of rats was extended by three days to one month,MRT,t1/2, Tmax of E2 in situ gel significantly increase and Cmax decreases, indicating that E2-IOG has a significant drug delivery capabilities in the presence of improving the burst release of drug in the body.In vivo results show that in situ gel formulations can achieve the effect of long-acting sustained-release by adjusting the structure and concentration of the gelator.This paper developed a good biocompatibility, biodegradable amino acid derivatives organic gel drug delivery system and clarify the advantages and drug release mechanism of the organic gels as sustained release drug storage, and provides a scientific basis for further study of the type of organic gel as of oral sustained-release drug delivery systems and in situ long-term sustained-release drug delivery system.