Preparation Of Caprolactam Thermo-sensitive Electrospun Nanofiber And Its Application In Drug Release

Electrospinning is a broadly used technology which utilizes electrical forces to produce fine fiber, and has become popular for the fabrication of polymeric biomaterials in recent years because it can produce fibers with controlled morphology, porosity, and composition by using simple equipment. The resultant nanofibers are particularly interesting for the field of biomedical engineering as wound dressing, tissue engineering scaffolds, and drug delivery carriers.Controlled drug release at a defined rate over a definite period of time is possible with biocompatible delivery carrier of polymers. Nanofiber mats have been applied as drug carriers in the drug delivery system because of their high functional characteristics and because the drug delivery system relies on the principle that dissolution rate of a particulate drug increases with increasing surface area of both the drug and the corresponding carrier. Moreover, the large surface area of nanofibers allows for fast and efficient solvent evaporation, which provides the incorporated drug limited time to recrystallize which favours the formation of amorphous dispersions or solid solutions. A number of researchers have successfully encapsulated drugs within electrospun fibers by mixing the drugs in the polymer solution to be electrospun. Depending on the polymer carrier used, the release of pharmaceutical dosage can be designed as rapid, immediate, delayed, or modified dissolution.Many intelligent drug carriers have been reported so far, including temperature-, pH-, magnetic field, electric field responsive systems. Temperature sensitivity is one of the most interesting properties in stimulus responsive systems among them and temperature is one of the best signals in terms of easy and safe medical applications. N-vinylcaprolactam (NVCL) is an important intermidate which is used to synthetize thermo-sensitive polymer of Poly(N-vinylcaprolactam)(PNVCL) series. PNVCL has not been studied as intensively as e.g. Poly(N-isopropylacrylamide), but it also possesses very interesting properties for applications of medical and biotechnological material, daily chemical production and other fields, e.g. solubility in water and organic solvents, temperature sensitivity, biocompatibility, high absorption ability and a transition temperature (33℃) in the range of physiological temperature.This investigation synthesized a thermo-sensitive copolymer PNVCL-co-MAA of different molecular weight by free radical polymerization of N-vinylcaprolactam (NVCL) and α-methacrylic acid (MAA). Then thermo-sensitive nanofibers were fabricated by combining with electrospinning means. At last, the studies which purposed to clarify biocompatibility of nanofibers and behavioural characteristic of nanofibers carring different drugs at different temperature were carried out.The main contents include:Using water as a reaction solvent, oxidation-reduction system as initiator system, NVCL and MAA as monomer, synthesized the temperature-sensitive polymer PNVCL-co-MAA. The conditions for synthesis were:NVCL concentration of4%(w/v), MAA concentration of0.4%(v/v), initiator APS concentration of0.16%(w/v). After that, polymer PNVCL-co-MAA was dissolved in appropriate organic solvent, and thermo-sensitive nanofibers was fabricated by combining with electrospinning means. By optimizing experiment, the results indicated that the optimum parameters were:mixed methyl alcohol and N,N-dimethylacetamide (DMAc) as solvent, volume ratio of85:15, spinning solution concentrition of0.1g/mL, inside diameter of flat syringe needle of0.90mm, aluminium foil as receiver, voltage of16kV, electrode distance of22cm.Four kinds of PNVCL-co-MAA polymer with different molecular weight were synthesized by changing the ratio of MAA in reaction system of polymerization process,0.2%,0.3%,0.4%,0.5%(v/v) respectively. Electrospun nanofibers which carried two kinds of drugs (hydrophobic Ketoprofen and hydrophilic Captopril) respectively were fabricated under optimum electrospinning condition mentioned above. A certain quantity of all samples dissolved in pH7.4phosphate buffer (PBS), and release test in vitro was carried out at different temperature. The results indicated that, fibers mat was more hydrophilic, dissolving fast, and drug release behavior showed rapid release at20℃(under LCST); conversely, fibers mat was more hydrophobic, dissolving slow, and drug release behavior showed modified release at40℃(above LCST). In addition, the higher the ratio of MAA was, the more slowly drug released because of chemical structure and steric hinerance of NVCL perhaps. The character of drug release was not only connected with nature of polymer materials itself, but also that of drug.The results of MTT test showed that the PNVCL-co-MAA nanofibers was not toxic to cells, and therefore was a kind of safe and no toxic polymer material.