Constrution Of Gel Drug-loading System Based On Tricyclic Triterpene Acid From Poria Cocos And Its Anti-breast Cancer Efficacy

Low molecular weight gels(LMWG)are a supramolecular system formed by low molecular weight gelling factors and solvents through complex non-covalent bonding including hydrogen bonding,hydrophobic interactions,and π-πinteractions.As a drug delivery system,LMWG has attracted many attentions due to its advantages of good biocompatibility,biodegradability and low toxicity.Our team’s previous research found a series of unmodified natural low molecular weight gelators,which have good biological activity and biocompatibility,and can form natural product gel without any modification.Based on the above research,this study isolated triterpene acid compounds with anti-oxidation and anti-tumor activity from natural product mash.The self-assembly gel was formed and used for the loading of the chemotherapeutic drug doxorubicin hydrochloride to construct a tricyclic triterpene acid gel drug-loading system,and its anti-breast cancer activity was studied.The main research contents are as follows:Firstly,the gel factor was separated and extracted from Poria Cocos,and its purity was determined to be 98%by high performance liquid chromatography.The gel was prepared by incorporation method,and the basic gel properties such as critical gelation concentration,phase transition temperature and rheological properties were tested.The results show that PAA can form a gel(PAA-Gel)rapidly in the ethanol water system,and has excellent gel properties,shear thinning and self-healing ability,and is an injectable gel carrier.SEM observation shows that the gel morphology is a network structure of fiber interlacing.Finally,the self-assembly driving force of PAA-Gel was studied by ultraviolet-visible spectrum,infrared spectrum and contact angle test,which proved that PAA-gel was formed by π-πinteraction and hydrogen bonding.Secondly,a gel drug carrier system with doxorubicin hydrochloride(DOX)as model drug was constructed(PAA-DOX Gel),and its anti-tumor activity in vitro was evaluated.The drug loading and rheological properties were further tested.The results showed that the basic gel properties of PAA-Gel did not change after the drug was successfully loaded,and it still had good rigidity and injectability.In vitro cytotoxicity test shows that PAA-DOX Gel has significantly better inhibitory effect on mouse breast cancer cell 4T1 and human breast cancer cell MCF-7 than free DOX group.Finally,a 4T1 tumor-bearing mouse model was established to study the in vivo release and antitumor activity of PAA-DOX Gel.The results showed that the PAA-DOX Gel group was significantly better than the free drug group.The pathological analysis of H&E and TUNEL immunohistochemical analysis showed that PAA-DOX Gel could induce apoptosis and necrosis of tumor cells.Evaluation of reduced drug side effects included mouse body weight change analysis,organ index analysis,cardiac H&E pathology studies,and effects on white blood cell count.The results showed that PAA-DOX Gel can effectively reduce the systemic toxicity of the drug,maintain the body weight stability of the mice;effectively inhibit the spleen enlargement and reduce the damage of the immune system;effectively protect the cardiomyocytes and reduce the toxicity of DOX HCL to the heart;PAA-DOX Gel also inhibits inflammation and congestion.The anti-oxidative ability of mice was analyzed.The results showed that the in situ injection of PAA-DOX Gel released the drug significantly increased the SOD activity in the serum of mice,indicating that the natural product also exerted its excellent antioxidant capacity.In summary,the successful construction of the natural product triterpene acid gel drug delivery system provides a new feasible way for drug delivery,and also provides a new idea for the study of natural product gel.