Construction Of Multi-walled Carbon Nanotubes Drug Carrier And Study Of The Drug-loading Mechanism

Insoluble durg is an important part in the new drug development.The poor water solubility has a direct impact on its bioavailability.Improve the dissolution can help the insoluble drug to improve its bioavailability.Therefore,it is necessary to ues the pharmaceutical means to improve the solubility of the poorly soluble drugs.Although carbon nanotubes have excellent mechanical,electrical and other characteristics,but its low solubility in solvents was greatly restricted its application.In order to make carbon nanotubes to be better applied in biomedicine,its dispersion must be improved.In this study,multi-walled carbon nanotubes(MWNTs)was used as a raw material.MWNTs were modified with a carboxyl group through the acid treatment,and then connected with other molecules.In this study,three insoluble drugs were using as model drugs.MWNTs were used as a carrier to load the modle drugs through three different methods(the fusion method,the incipient wetness impregnation method,and the solvent method).And then the dissolution was determined.The results showed that CNT had a high drug loading.The drug loading of samples made by the solvent method was determined by adsorption time,drug concentration,solvent,ultrasonic conditions.The carbon nanotube drug delivery system could improve the dissolution of the insoluble drugs.Among them,the samples loaded CAR has a shorter adsorption equilibrium time and larger drug loading.So we used CAR as a model drug for subsequent trials.PAMAM,with a high degree of geometric symmetry,a large number of surface functional groups,molecular memory,are widely used in the field of medicine.In this study,methyl acrylate and ethylene diamine were used as raw materials to prepare G3.0 PAMAM through repeated Michael addition reaction and amidation reaction.Infrared spectrum of the product was agreed with the literature.PAMAM-MWNTs were prepared by condensation reaction.The increased amide peaks in the infrared spectra was indicated that PAMAM and MWNTs had been connected through the condensation reaction.The PAMAM-MWNTs had a better dispersion than the unmodified MWNTs.PAMAM-MWNTs was stable in HC1(pH=1)、PBS buffer(pH=6.8)and distilled water.The effects of different pore size,specific surface area and physical state were systematically studied using scanning electron microscopy(SEM),thermogravimetric analysis(TGA),Fourier transformation infrared spectroscopy(FT-IR),differential scanning calorimetry(DSC),nitrogen adsorption,X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS).Experimental results showed that the method of drug loading determined the physical state of the drug and the distribution of the drug in the carrier,thus effected the dissolution and solubility of drugs.The sample made by the fusion method had a drug release of 80%within 1 hour,which could be applied to immediate-release drug delivery systems.The sample made by the solvent method released slowly and could by applied to the sustained release drug delivery system.In addition,the dissolution rate could be adjusted by the drug loading,so we could achieve our ideal release effect.Therefore,the establishment of carbon nanotube delivery system could establish a reference for the immediate release,sustained release drug delivery system of other insoluble drugs.In addition,we studied the degradation of PAMAM-MWNTs under the conditions of artificial gastric juice and artificial intestinal fluid,and no degradation was found.Gastrointestinal irritation and cell toxicity experiments showed that the CNTs had less gastrointestinal irritation and toxicity on Caco-2 cell.It could be well used in oral administration.The pharmacokinetic studies showed that the bioavailability of the CAR capsule increased slightly comparing with the commercially available tablets.