Preparation And In Vitro Release Of PH Sensitive Cyclodextrin Micelles Loaded With Paclitaxel

Amphiphilic copolymers can be self-assembled to form micelles and other assemblies.Polymeric micelles have many advantages as pharmaceutical carriers in the application of drug delivery systems.Paclitaxel as a clinical application of more anti-cancer drugs,due to its poor water solubility,greatly reduced its efficacy.Therefore,the development of a drug carrier that increases the solubility of paclitaxel and reduces the toxic side effects has been a hot spot in the field of hydrophobic drug delivery systems.Amphiphilic polymer materials can determine the performance of polymer micelles.In this paper,a Schiff base reaction occurs with mono-6-formyl-deoxy-p-cyclodextrin and octadecylamine to form an amphiphilic polymer with dynamic covalent bond.The imine bond in polymeric micelles can be broken under acidic conditions to release the hydrophobic drug paclitaxel.A pH-sensitive drug carrier was constructed,and the physicochemical properties and in vitro release of drug-loaded micelles were further studied.Mainly includes the following content:(1)Cyclodextrin derivatives were synthesized by modification of the hydroxyl group at the 6-position of β-cyclodextrin.The resulting cyclodextrin derivatives and block copolymers were characterized.(2)Taking 6-β-CD-N-ODMA as material and taking anticancer drug paclitaxel as model drug,drug-loaded micelles were obtained by dialysis method so as to increase paclitaxel.Then the orthogonal test was used to optimize the preparation method of drug-loaded micelles.The optimum conditions were as follows:DMF 5ml,paclitaxel 3mg,materials 50mg and water 2ml.The drug-loaded micelles prepared by this process have a drug loading of 1.97%.(3)The physicochemical properties and in vitro release properties of the prepared PTX/6-β-CD-N-ODMA micelles were investigated.The average particle size of drug-loaded micelles was 261.6nm,the PDI was 0.235 and the Zeta potential was 20.3mV which measured by dynamic light scattering.The shape of PTX/6-β-CD-N-ODMA micelles was observed as rod-like structure by scanning electron microscopy.The drug release properties of PTX/6-β-CD-N-ODMA micelles in pH 5.0 and pH 7.4 buffer solutions were investigated.The results showed that the micelles were pH-sensitive.