Thermosensitive Polypeptide-based Hydrogels:synthesis And Antitumor Application

Polypeptide hydrogels have a wide research space and market prospects because of their advantages such as injectable,biodegradability and biodegradability.In the biomedical field,hydrogels are often used as carriers for drug delivery,scaffolds for tissue engineering and 3D cell culture.Especially,drugs are carried out by degradation of the hydrogel and diffusion by itself when hydrogels are used as a drug carrier.The degradation products of polypeptide hydrogels don’t cause pH changes in suit compared with polyester hydrogels.In addition,the cross-linking method of polypeptide hydrogels is physical gelation.The advantage of the method is that it will not introduce organic small molecules,and it is safer than chemical cross-linking.However,the mechanical strength of the hydrogel formed by physical cross-linking method is lower,and the hydrogel formed may exhibit initial burst release when it is used as a carrier for drug transport.In this paper,in order to solve these problems,we designed and prepared functional hydrogels,and evaluated the gelation behavior,gelation mechanism and biocompatibility of hydrogels.Furthermore,the CDDP and the mouse colon tumor cells C26 were used as models in this study.The specific steps are as follows:1.The use of controlled methods to improve the performance of hydrogels is the only way to break the limitations of the original application.It is known that the hydrophobic groups facilitate the enhancement of the mechanical strength of temperature-sensitive hydrogels.Here,we prepared six kinds of methoxy-poly(ethylene glycol)-b-(poly(γ-ethyl-L-glutamate-co/b-L-pHenylalanine)(mPEG-b-(PELG-co/b-PLG))with different ratios and different sequences by ring-opening polymerization.All of the six polymers in the phosphate buffer solution(PBS)undergo a sol-gel transitions as the temperature increases,and the sol-gel transitions temperature drop and rise then as the hydrophobicity(L-phenylalanine)increased.In contrast,the elastic modulus shows the tendency of rising first and then decreasing.At the microscopic level,the secondary structure of the peptide(random coil,α-helix,and β-sheet)on the behavior of the gel was observed by(CD)and FTIR spectra.The results showed that this anomaly was due to the incorporated random coil.In summary,the results of the study offers more possibilities for the application of polymers.2.The initial burst release is a major limitation of injectable implants in situ drug delivery system.In this paper,we have developed an injectable heat-sensitive peptide cisplatin(CDDP)composite hydrogel that was used to improve CDDP release behavior and enhance the local anti-tumor efficacy.The methoxy-poly(ethylene glycol)-b-(poly(γ-ethyl-L-glutamate-co-L-glutamic acid)(mPEG-b-(PELG-co-PLG))not only changes in mechanical properties,but also can reduce the outbreak of hydrogel release effect through CDDP-complexted.Furthermore,the mPEG-b-(PELG-co-PLG)hydrogel has good biocompatibility and biodegradability in vivo.However,compared with the control group,a significantly lower IC50 was shown in vitro,and the anti-tumor efficacy of the CDDP composite hydrogel had a significant improvement in vivo.In summary,this injectable CDDP composite hydrogel may be a potential drug to improve local anti-tumor drug delivery.