Study On Preparation Of Podophyllotoxin-loaded Nanomicelles

Due to its special structural properties,micelles are often used as carriers for poorly soluble drugs in drug delivery systems.Some poorly soluble drugs are often encapsulated in the hydrophobic core of micelles by appropriate drug loading methods,thereby improving the solubility of poorly soluble drugs.targeting,stability,etc,improve the bioavailability of drugs in the body.In this paper,two commonly used polymer materials,mPEG-PLGA(methoxy-polyethylene glycol-polylactic acid-glycolic acid copolymer)and mPEG-PTMC(methoxy-polyethylene glycol-polytrimethylene carbonate)were selected.The traditional Chinese medicine component Podophyllotoxin(POD)is loaded by an appropriate drug-loading method to improve the insufficiency of POD for anti-tumor treatment.Two kinds of polymer micelles were studied before the formulation of POD.Firstly,two groups of drug-loaded micelles were screened by single factor,and their formulation was optimized by star design-response surface methodology.Drug loading efficiency(DLC)and entrapment efficiency(DLE)of mPEG-PLGA group were as high as 7.45%(+1.06)and 85.28%(+0.136),respectively.The drug loading and encapsulation rates of mPEG-PTMC group were as high as 6.7%(+0.08)and 84.13%(+2.87),respectively,and the results were reproducible.Characterization of drug-loaded nanomicelles: A series of characterization methods were used to characterize drug-loaded micelles.Including the comparison of particle size of micelles before and after drug loading,a series of stability studies of drug-loaded micelles,determination of POD phase in Drug-loaded micelles,hemolysis experiments of polymer micelles and morphology of erythrocytes,etc.The results show that the prepared drug-loaded micelles have smaller particle size,and a series of stability measurements also show that the drug-loaded micelles prepared by us can be well adapted to all aspects of stable investigation.Pharmacodynamic evaluation of drug-loaded micelles in vitro and in vivo: It was found that drug-loaded micelles could be absorbed by cancer cells and released into the nucleus of cells.In vitro evaluation results showed that blank micelles had little toxicity to the selected two kinds of cancer cells.On the contrary,drug-loaded micelles had significant inhibitory effect on the two kinds of cancer cells in a concentration-dependent manner,the inhibitory rate was high at high concentration,but relatively low at low concentration.In vivo studies of two drug-loaded micelles showed that nano-drug-loaded micelles could reduce the toxicity and side effects of drugs on normal tissues and the growth rate of tumors compared with naked micelles.Based on the above analysis,the preparation of two drug-loaded micelles for anti-tumor treatment will have a good application prospect.