Design And Synthesis Of Gemcitabine Hydrogel And Its Anticancer Effect In Pancreatic Cancer

Gemcitabine as a basis for combined with other chemotherapeutic drugs(NAB paclitaxel and s-1) is for the frontline treatment of pancreatic cancer chemotherapy,but included gemcitabine and most other chemotherapy drugs generally have poor water solubility, serious side effect and low loading efficiencies problems. To improve the water solubility, reduce the side effects, the application of polymeric micelles, polymeric nanoparticles are currently being extensively used, but these nanocarriers have low drug loading rate and difficult to fabricate. The small molecular peptide hydrogel has wide application foreground in controllable delivery of therapeutic agents and regenerative medicine aspact, they can increase its water solubility and can also be more effective drug targeting in cancer cells and tumor tissue. This paper aim to increase the water solubility and loading efficiencies through the gemcitabine and peptide binding to make drug derivatives, the derivative can self-assembly into hydrogel, and it can deliver drugs through chemical reactions and enzyme catalyzed reactions, it may be widely used as new durg delivery system.Methods1.Synthesis and characterization of small molecular peptide: solid phase peptide synthesis was used to obtain four small molecule peptide chain: GFFYGRGD,GFFYGRGE, FBA-GFFYGRGD, FBA-GFFYGRGE; RP-HPLC was used to purify small molecule peptide; using H NMR and LC-MAS to confirm the structure of small molecular peptide.2. Preparation and characterization of Gemcitabine-loaded small molecules hydrogels: design a hydrogel system based on Schiff base formation; Rheology was performed to characterize the mechanical properties of the resulting hydrogels;Transmission electron microscopy(TEM) was then used to characterize the morphology of nanostructures in the peptide solutions and the hydrogels; the release behaviour of gemcitabine from the gel at 37 ? performed to study the release rate of gemcitabine at different pH values.3. Anti-cancer study of gemcitabine–peptide: MTT cell viability test was alsoused to measure the IC50 values of gemcitabine and gemcitabine–peptid conjugates to pancreatic cancer cells.Results1.Using solid phase peptide synthesis of small molecule peptide crude product yield up to 90%, After RP-HPLC, the purity of small molecular peptides reached more than 95%.2. Gemcitabine-loaded small molecules hydrogels were formed through the Schiff base formation; the rheolgy results show that gemcitabine-loaded small molecular hydrogel has good anti pressure, anti shearing force; TEM results indicated that the addition of gemcitabine to the nanofiber, the nanofiber was longer, thicker,and they entangled with each other to form a dense hydrogel forming network;Release profile of gemcitabine from gel at different pH values suggested that in the acidic environment, the gemcitabine release rate was higher.3.MTT results suggested that, gemcitabine–peptide conjugates possessed better inhibition capacities to pancreatic cancer cells comparing with the free gemcitabine.Conclusion1. Gemcitabine can be combined with small molecule peptide to form a hydrogel through the schiff base formation, it can effectively improve the loading efficiency and solubility of gemcitabine.2. Due to supramolecular nanofibers and hydrogels have good biocompatibility and responsiveness they hold great promise for controllable delivery of therapeutic agents; Gemcitabine-loaded small molecules hydrogels can not only improve the water solubility of Gemcitabine, but also increase the drug targeting.