Study On Supramolecular Hydrogel Based On MPECT Nanoparticles And ?-Cyclodextrins For Drug Delivery

Supramolecular hydrogel has broad prospect of application in the field of biomedicine.A novel injectable and high-solid-content drug-loaded supramolecular hydrogel(PTX-mPECT NP/?-CD^gel)was prepared by self-assembly of inclusion complexes based on PTX-loaded mPECT?methoxy poly?ethylene glycol?-b-poly??-caprolactone-co-1,4,8-trioxa[4.6]spiro-9-un-decanone??nanoparticles?PTX-mPECT NPs?and?-cyclodextrin??-CD?in this paper,which could solve the problem that the hydrogels have poor loading ability of hydrophobic drugs.In the first part,gelation occurred when the aqueous solution of?-CD was added into the PTX-mPECT NPs aqueous dispersion within several seconds after stirring.It was proved that the hydrophobic cores formed by self-assembly of amphiphilic polymer mPECT and the microcrystals of polypseudorotaxanes formed by?-CD and PEG blocks could serve as two-level cross-linkings for the gel formation.PTX-mPECT NPs aqueous dispersion with different DLC presented uniform size and stable structures and PTX-mPECT NP/?-CD^gel displayed a uniform network structure,which means this system could effectively load PTX.Additionally,the gel with highest drug loading content has greater strength and the internal structure was more closely.Rheological studies showed that PTX-mPECT NP/?-CD^gel with good injectability underwent a shear-induced sol-gel transition.Importantly,with the erosion of the hydrogel,PTX-loaded NPs could be released again and then PTX released further.The results of in vitro drug-release studies demonstrated a sustained-release behavior,and the cumulative release of PTX was about 35%after 20 days.And then,as a local drug delivery system for chemtherapy,the biocompatibility and antitumor effect of PTX-mPECT NP/?-CD^gel were evaluated in vitro and in vivo.The mPECT NP/?-CD^gel exhibited nontoxic in the short-term or long-term cytotoxicity assay in vitro.Additionally,the results of cell-uptake studies and in vitro cytotoxicity studies indicated that the PTX-loaded NPs have been delivered to cells and killed tumor cells efficiently.And its nano-structure will contribute PTX-loaded NPs with higher cytotoxicity compared with free PTX.Smaller size of tumor volumes and higher suppression of tumor growth demonstrated the remarkable anticancer effect of PTX-mPECT NP/?-CD^gel upon peritumoral injection.Significantly,via peritumoral administration,PTX-mPECT NP/?-CD^gel showed good biocompatibility and nontoxicity to other normal tissues.These results showed that high-solid-content PTX-mPECT NP/?-CD^gel based on in situ systems could be a promising candidate for local precise chemtherapy.