Carboxymethyl-?-cyclodextrin Grafted Chitosan As Drug Nanocarrier And Hypoglycemic Effect Of Oral Insulin/carrier

Chitosan(CS)is a cationic natural polymer derived from chitin by partial deacetylation.Because of its non-toxic,biocompatible,biodegradable and mucoadhesive properties,CS is widely used in the pharmaceutical field as oral carrier systems for protein drugs.Cyclodextrins(CDs)are basket-shaped molecules that have a hydrophobic central cavity and a hydrophilic outer shell.The hydrophobic chamber of CDs is able to interact with various hydrophobic domains of guest molecules forming non-covalent inclusion complexes.In this paper,the Carboxymethyl-?-cyclodextrin(CMCD)was grafted onto CS,and then the CMCD grafted CS nanoparticles(CMCD-g-CS NPs)were prepared based on ionic gelation mechanism of anionic TPP.The physicochemical properties of the prepared CMCD-g-CS NPs were characterized by modern analytical technology,for example,fourier transforms infrared spectroscopy,nuclear magnetic resonance,transmission electron microscopy and dynamic light scattering etc.Bovine serum albumin(BSA),a model protein drug,was loaded in prepared nanocarriers with ideal entrapment efficiency(EE)and loading content(LC).The drug release profiles of BSA loaded nanoparticles were studied in simulated gastric fluid(SGF),simulated intestinal fluid(SIF)and simulated colonic fluid(SCF).It was found that the drug loaded nanovehicles displayed a typical sustained controlled release profiles and the amount of BSA released from the nanocarriers was much higher in SIF and SCF than it in SGF.The research results suggested that the CMCD-g-CS NPs had the potential as promising nanocarriers for oral delivery of protein drugs.Then,the CMCD-g-CS NPs were used as insulin delivery carrier for improving the therapeutic efficacy of oral drug.The prepared nanocarriers exhibited favorable loading capacity and encapsulation efficiency of insulin.The release experiment in vitro showed that the nanocarriers could efficiently protect insulin at SGFenvironment and release drug in the SCF.The oral administration of insulin/CMCD-g-CS NPs effectively promoted drug internalization into Caco-2 cell and augmented hypoglycemic effect in diabetic mice.The liver function study verified that the CMCD-g-CS NPs had not obvious toxicity to experimental mice.Therefore,the CMCD-g-CS NPs could be effective and safe oral insulin delivery carriers for future clinical application.