Fabrication Of Acid-responsive Electrospun Fibrous Scaffolds Based On Sodium Bicarbonate For Drug Carrier

Electrospun fibers have been widely studied as tissue regeneration,growing engineering scaffolds and drug delivery. At present, theapplication of electrospun fibers as tissue engineering and acid-responsivedrug carriers have been studied and have initial progress, but there are stillsome problems that needed to be solved, for example, the unsustainable ofthe scaffolds, fast initial release and long-term release control are causedby the large specific surface area and the high responsivity. In order toaddress these issues, the sustained acid-responsive electrospun fibers werefabricated by adding SB into the fibers, and the anti-inflammation andanti-tumordrugs were used as drug model to investigate theacid-responsive release and long-term acid-responsive release of the drugs.The composite fibers as long-term release drug carriers were studied andthe smart long-term short-term acid-responsive dual drug-loaded scaffoldswere investigated.First, PLLA-SB composite fibers were fabricated via blendingelectrospinning, the SB was fabricated into the electrospun PLLA fiberswith IBU and5-Fu separately. The results show that the morphologies ofthe fibers were smooth, indicating that the loaded drugs and SB werehomogeneous distributed. In the acid environment, the total drug releaserate of electrospun PLLA/SB fibers was higher than PLLA fibers, and therelease rate increased along with the increase of SB. The electrospunPLLA/SB fibers with the same content of SB had higher release rete in theacid environment than the neutral environment. After the in vitro release,the PLLA/SB composite fibers maintained the original structure and morphology. The cell environment experiment shows that cell attachmentwas improved and the cell proliferation rate was enhanced on thePLLA/SB electrospun scaffolds. A novel acid-responsive electrospunfibrous scaffold was easily fabricated, which provided a rapidacid-responsive controlled drug release (early stage) and stable3Dstructure as tissue engineering scaffolds (late stage) for cell growth.Secondly, the DOX was pre-loaded into the MSNs, then theelectrospun PLLA-(MSN-DOX)-IBU composite fibers were fabricated viacosolvent electrospinning. The results showed that the (MSN-DOX)nanoparticles could be wrapped into the fibers and the surfaces of thefibers had rough secondary structures. This particular structure made theelectrospun PLLA-MSN-DOX composite fibers had small initial burstrelease, long-term release and could realize the long-term drug release. Incontrast, the release of IBU was relatively quick and had higher totalrelease rate. The electrospun composite fibers maintained their originalstructure. Therefore, the IBU that were fabricated directly into the fibersmay realize the effect of inhibiting inflammation at the initial stage, whilethe anti-tumor drug which was pre-loaded in the MSNs then fabricated intothe electrospun fibers had the effect of long-term release, so the compositefibers had multiple functions of inhibiting inflammation at the early stage,anti-tumor in long-term and repair tissue.At last, based on the experiments above, SB was combined into theMSNs via electrostatic adsorption, PLLA-(MSN-DOX)-SB-IBU fiberswere fabricated via cosolvent electrospinning. Study results show that the(MNS-DOX) and (MSN-DOX)-SB were successfully fabricated by thecosolvent electrospinning method. In the in vitro release profile of DOX,the electrospun PLLA-(MSN-DOX)-SB fibers had lower total release rateand longer release period. The electrospun PLLA-(MSN-DOX)-SB-IBUfibers had fast short-term release profile of IBU and relatively slow andlong-term release profile of DOX. The electrospun fiber becameacid-responsive because of the existence of SB. The release of DOX became acid-responsive and could be adjusted by the content of SB andDOX. Therefore, the composite fibers which had the effect of inhibitinginflammation at the early stage and releasing anti-tumor drug for long-termcould be fabricated by pre-load SB into the MSNs.In conclusion, in this paper, SB was fabricated into the electrospunfibers in different ways, to realize the acid-responsive release of theanti-inflammation drug IBU and the anti-tumor drug5-Fu, and thestructure of the electrospun fibers was maintained. The electrospun fiberswhich had the effect of the quick release of anti-inflammation drug and thelong-term release of anti-tumor drug were fabricated by pre-loading druginto the MSNs. Further, the acid-responsive, long-term, adjusted release ofthe anti-tumor drug DOX was achieved by pre-loaded the SB into theMSNs. Therefore, this paper offered a new method for the smartacid-responsive release of drug, the tissue repair, it also offered a newthought for the clinical integration tissue repair.