Preparation Of Polyamino Acid-based Physical Hydrogel For Local Drug Delivery

Thermal-sensitive hydrogel is a common drug carrier in the field of biomedicine.Because of its simple gelation mechanism,it is easily to be mixed with drugs at low temperature and easy to inject.It can slowly degrade after thermal-sensitive gelation and release drugs,but due to the traditional polyester thermal sensitive condensation gelatinization require high concentrations,difficult to change performance,and produce acidic stacks,which have certain limitations.In order to solve the above problems,we prepared polyamino acid thermal-sensitive hydrogels with excellent performance,evaluated the gelation performance,safety,and degradability.At the same time,we carried chemotherapeutic drugs Doxorubicin（DOX）and Erlotinib（Erl）to evaluate the application of these drug carriers in anti-tumor.The process details are as follows:（1）Three polyalanine copolymers with different degrees of polymerization were prepared by ring-opening polymerization（ROP）.These kinds of copolymers could underwent phase transition in phosphate buffer solution（PBS）,and the gel transition temperature decreases as the degree of polymerization increases.The formed hydrogels could be rapidly degraded in the presence of protease-K andα-chymotrypsin,and no inflammatory response could be generated at any time during the degradation process,and its had good safety.（2）Polyproline copolymers of three different degrees of polyvaline were prepared by ROP.These polymers could underwent phase changes in PBS.It was found that the gelation mechanism was similar to that of polyalanine.And it could be used as an injectable drug carrier,Post-treatment of human non-small cell lung cancer（A549）tumors with DOX and Erl hds significant effects and does not produce significant toxicity;（3）Three kinds of leucine copolymers with different degrees of polymerization were prepared by ROP.Select one of the copolymers and find that the gel had good performance,and the gel degradability is suitable,and it will not produce inflammatory reactions during degradation.This hydrogel was used in conjunction with a poly（L-lysine）-poly（L-phenylalanine-co-L-cysteine）(PLL₁₀-P(LC₅-co-LP₁₀))drug delivery core to treat A549 tumors and MCF-7/ADR tumors were found to have very good tumor suppressor ability.This polyamino acid thermosensitive gel has a simple synthesis step,good gel properties,degradability and safety.In the field of biological materials has a good development prospects.