Local In Vitro Delivery Of Rapamycin From Electrospun PEO/PDLLA Nanofibers For Glioblastoma Treatment

ObjectiveTo establish the safe and effective sustained release system with rapamycin(Rapa),which based on polyethylene oxide ethane/poly(D L-lactic acid)(PEO/PDLLA)for control-released carrier materials,making the drug released slowly and smoothly from the carrier,it also reduce the local neurological side effects because of the sudden release.By in vitro cytotoxicity experiments to explore the antitumor effect of U 87 and U251 glioma cells.Method(1)Different ratio of materials was made by electrospinning technology without drug fiber membrane which aimed to determine the best ratio between the two materials.And then added different amounts of Rapa to built the drug-loaded membranes.Nanofiber morphology was analyzed by scanning electron microscopy.The physical state of Rapa within the fibers was investigated by X-ray diffraction(XRD)and fourier transform infrared(FT-IR).Water contact angle was measured to evaluate the hydrophilic and hydrophobic of membranes.(2)To determine the encapsulation efficiency(EE)and drug-loading rate within the fibers.Rapa-loaded PEO/PDLLA electrospun meshes were incubated in 5 ml PBS which placed in a water bath at 37? and 60rpm/min.At predetermined time points.samples of medium were collected and replaced with an equal volume of fresh PBS.Rapa concentration was measured by high-performance liquid chromatography(HPLC).According to the amounts of Rapa released from fibers and cumulative amounts of drug to formulate the drug release curve.And to observe the degradation state of the fibers by SEM after three and seven days respectively.(3)After sterilization by irradiation with cobalt-60,membrane samples loaded with different concentrations of Rapa(0,0.5,1,and 2 wt%)were placed in a 96-well containing U87 and U251 tumor cells.The medium was changed daily,and the plates were incubated for 1,3,5,7 days,the cell viability was assayed with Cell Counting Kit-8.ResultThe surface of different amounts of drug-loaded fibers was smooth with a uniform diameter after selecting the best ratio of PEO and PDLLA and without seeing obvious drug crystallization.The FT-IR peak which was observed for drug powder was also observed in the spectra of the Rapa-loaded nanofiber meshes,indicating that the drug chemical functional groups were not damaged during the electrospinning.The results of XRD showed that the low amount of Rapa and PEO-PDLLA interactions that hindered crystal formation.Blending fibers' crystallinity was lower than that of each material and drug itself.The degradation process of fiber membrane was consistent with the drug release curve.The releasing rate and time was different from each membrane due to the different drug loading rate.but all of them showed the ability of constantly inhibiting glioma cells in vitro.Among them,the membrane with 1wt%Rapa exhibited more stable and persistent antitumor activity with little sudden released.ConclusionRapa-loaded composite nanofiber by using biodegradable materials PEO and PDLLA as a sustained delivery system is feasible which has good physical and chemical properties.While the drug concentration is increased within a certain range,the release time of drug will be increased accordingly and more stable.The 1wt%Rapa-loaded PEO/PDLLA nanofiber exhibited better advantages which could be a method for local chemotherapy following surgery.