The Preparation And Properties Of Combined Drug Delivery Micellar System Of CLB And DOX

The tumor is a diseases seriously harm to human health currently,and along with the rising incidence,so the treatment of malignant tumors has become the biggest challenge today.Traditional single antitumor drugs have many defects in the course of treatment,such as low bioavailability of drugs,long-term single drug will produce tumor resistance,thus using the way of drug combinations to reverse the resistance of the tumor usually.Doxorubicin(DOX)and Chlorambucil(CLB)are used in clinical treatment of bone tumors,lymphoma and so on,but they are both poor water solubility,and DOX is easy producing drug resistance and high toxicity.Therefore,this paper uses the polymer nano-carrier with reducing response to load two drugs at the same time to achieve the purpose of overcoming tumor resistance,accelerating drug release,reducing dosage,reducing toxicity and improving biocompatibility.In this paper,we designed a hydrophilic segment with L-cysteine as the central molecule,Fmoc as the hydrophobic segment and PEG(750)with the disulfide bond as the crosslinking agent,then binding the anti-cancer drug CLB to form redox-stimulated responsive amphiphilic drug-loading compounds,and another anti-cancer drug DOX was loaded into the micelles by the method of physical embedding,then polymer nanocomposite micelles of PEG-SS-Cys-CLB/DOX was designed.The structure of the amphiphilic drug-loaded compound was analyzed and characterized by 1H NMR and MALDI-TOF-MASS.The critical micelle concentration was 0.01 mg/mL by measuring the fluorescence probe pyrene.The drug loading of DOX was 7.6%by UV spectrophotometer.The particle size,Zeta potential and polydispersity index(PDI)of the micelles,respectively,were 12.43 nm,-1.37 and 0.413 by measuring the dynamic light scattering instrument(DLS).The minimum critical melting point of polymer nanocomposite micelles was 53 ? by means of micro melting point spectrometer.The in vitro drug release properties of the polymer nanocomposite system were tested using an ultraviolet spectrophotometer,the maximal release rate of CLB was 81.7%,and the maximum cumulative drug release rate of DOX was 86.5%.The combined administration of the micellar system has a reduced susceptibility targeting,rapidly released in tumor tissue,good stability,long circulation,and high bioavailability of the drug.So as to avoid using a single drug for a long time to produce cancer resistance,providing a potential application value.