Fabrication Of Self-Nanoemulsifying Fibrous Membrane And Its Biomedical Application

Objectives:To fabricate self-nanoemulsifying fibrous membrane(SNE-FM)enhancing drug permeation for the purpose of promoting topical therapeutic effect by compositing self-nanoemulsifying drug delivery system(SNEDDS)into electrospun fibers.Methods:SNEDDS and polymers were co-dissolved in organic alcohol solvent for blend electrospinning of SNE-FM.The SNE-FM was investigated from the perspective of micro-morphology and macro-performance by SEM,FI-TR,universal mechanical tester,DLS and SAXS.Its effect of drug permeation enhancement after self-nanoemulsifying was determined with a Franz Cell experiment and an artificial connective tissue model experiment.A modified Valia-Chien device was applied to investigate the release profile of the SNE-FM simulating the conditions under which a patch should go though in application.The biocompatibility of the SNE-FM was evaluated with Live/Dead staining and CCK-8 assay.Moreover,a rat model of rheumatoid arthritis was induced by Freud's adjuvant complete to evaluate the in vivo performance of an ibuprofen-laden SNE-FM treating acute inflammation.Results:SNE-FM was successfully fabricated with smooth and uniform micro-morphology.The SNE-FM showed a robust mechanical performance,and it was found that incorporation of certain amount of SNEDDS promoted the mechanical strength and stability of the fibers.The SNE-FM also showed the function of self-nanoemulsifying as it was expected,and the nanoemulsion thus produced enhanced the transdermal permeation and diffusion in connective tissue model.The drug release profile of the PLLA-based SNE-FM fitted Ritger-Peppas model and demonstrated its potential to be rationally regulated by adjusting the amount of incorporation of SNEDDS and drug.Furthermore,the SNE-FM was of good biocompatibility,showing no significant influence on the adhesion,growth and proliferation of fibroblasts.Meanwhile,the SNE-FM was proved to be more effective compared to regular drug-laden fibrous membrane in inhibition and relief of the acute inflammation in vivo.Conclusions:In this study,SNE-FM was fabricated for the first time for delivery of nanoemulsion which promoted drug absorption and permeation.The SNE-FM showed stable performance of self-nanoemulsifying and enhanced drug permeation both in vitro and in vivo,as well as promoted therapeutic effect in vivo.This study provided topical drug delivery with a new strategy of cost-effectivity,good controllability and handleability.