Design And Preparation Of Novel β - Cyclodextrin - Chitosan Amphiphilic Polymer CCP1221 And Preliminary Study On Reversing Cell

To decrease the toxicity and side effect of Adriamycin, an amphiphilic copolymer micelles drug delivery system composed of chitosan and β-cyclodextrin which could improve the solubility and clinical applicability of Adriamycin was prepared. A higher solubility and better performance of controlled release of drugs in these micelles could be obtained through the self-assembly of micelles. It is promising to utilize these nanoparticle micelles as a drug carrier beacuse the narrow distribution of particle size and the stable core-shell structure bring micelles numerous advantages for example the facility to encapsulate hydrophobic drugs, the enhancement of accumulation and permeability of drugs in tumor tissues which could achieve an passive targeted effect. Researches described as below were carried out in this paper:Based on the structure of chitosan, maleic anhydride was introduced as a hydrophilic chain through maleylated reaction while the structures of oleic acid and β-cyclodextrin were introduced as hydrophobic moieties through oelylated reaction and Michael addition respectively. The synthesized product was characterized by FT-IR and 1H-NMR which demonstrated the success of the synthesis of copolymers. The substitution degree of structures of each unit was calculated. The substitution degree of p-cyclodextrin and malyel was 6.8% and 17.4% respectively while that of oleyl was ranged from 5.4% to 8.9%.The technologies of fluorescence probe method and dynamic lighting scattering method were employed to determine the critical micellar concentration and the size distribution of nanoparticles. The results showed that the CMC was ranged from 0.015 to 0.046 mg/mL while the particle size of micelles loading ADR or not was ranged from 193.6 to 242.5nm and 237.6 to 289.8 nm respectively. The loading content and encapsulation efficiency was ranged from 5.35% to 7.72% and 61.7% to 78.05% respectively. About 63.19% ADR was freed away from micelles in drug in vitro release experiment.The cytotoxicity of micelles without drugs to MCF-7 cell lines and MCF-7/ADR cell lines was analyzed through MTT method which ascertained the suitable range of concentration of micelles used in followed treatment was from 0.25mg/mL to 1 mg/mL. Under the same method, the IC50 value of mixture of ADR and CCP1221 copolymers at different concentrations to MCF-7/Adr cell lines was determined. The reversal effect fold could be acquired by comparing the IC50 values obtained in experiments above. The results demonstrated that the reversal effect of CCP1221 copolymer was ranged from 3 to 15.82 folds to free ADR in MCF-7/ADR cell lines.