Preparation Of Water-stable Zein-based Electrospun Fibers And Drug Release Properties

With the development of drug synthesis and drug screening technologies,the number of poorly water-soluble drugs keeps rising.The bioavailability of drugs and their clinic performance are seriously limited by their poor water-solubility,which also puts forward a higher demand for drug delivery systems.Therefore,an improvement in the dissolution of poorly water-soluble drugs has become a hot research topic in the medical and pharmaceutical fields.As typical representatives of electrohydrodynamic technology,electrospinning and electrospraying,which can transform poorly water-soluble drugs into amorphous states,have been considered as effective methods to produce a new generation of solid dispersions.Additionally,electrospun nanofibers are regarded as potential materials for wound dressings and tissue engineering scaffolds,due to high specific area,high porosity and nano-scale 3D fibrous structures,which can mimic the extracellular matrix.In this paper,a poorly water-soluble non-steroidal anti-inflammatory drug indomethacin(IND)was used as a model drug.Plant protein zein with good biocompatibility was co-electrospun with water-stable cellulose derivative ethyl cellulose(EC)to prepare the drug-loaded zein/EC electrospun nanofirous matrix.The influence of different zein/EC ratio on fiber morphologies,surface wettability,water-stability and mechanical performance was studied to select an optimal zein/EC electrospun nanofibrous matrix,on which in vitro drug release experiments were conducted.Results showed that the fiber morphologies were desirable when the ratio reached 1:1.X-ray energy dispersion mapping showed that IND was evenly distributed in the fibrous matrix.All the components were only mixed physically,and IND was transformed into amorphous states according to the result of physical states analysis.The drug-loaded zein/EC(1:1)electrospun nanofibrous mat displayed desirable water-stability and mechanical performance,and was selected as the matrix.The in vitro drug release experiments revealed that the dissolution of IND was improved when loaded in the electrospun zein/EC(1:1)nanofibers.However,further enhancement was still needed in the dissolution profile.Based on electrospun zein/EC(1:1)nanofibers,water-soluble polymer polyethylene oxide(PEO)was introduced,and drug-loaded electrospun zein/EC/PEO fibers with different PEO contents were prepared.The impact of PEO contents on the fibrous morphologies,surface wettability,water stability,mechanical performance and drug release properties was discussed.Besides,in vitro cytotoxicity assay was also performed to evaluate bio-compatibility.The results revealed that the average fiber diameter increased with the addition of PEO.A bimodal distribution of fiber diameter was observed when the content of PEO was 5%.Surface wettability was improved by the introduction of PEO,with good water-stability maintained.The Young's modulus was enhanced by PEO.According to the result of in vitro drug release experiments,PEO improved the dissolution of IND at the initial stage.The improvement was most noted when 10% PEO was added.Electrospun zein/EC/PEO fibers showed good bio-compatibility according to the cytotoxicity assay.In order to mimic the extracellular matrix and make the best of the electrospun nanofibers,drug-loaded fiber/particle nanocomposites were prepared via simultaneous electrospinning and electrospraying.Drug-loaded zein/EC nanofibers were produced by electrospinning.Meanwhile,electrospraying was conducted to produce drug-loaded PEO nanoparticles.IND and tetracycline hydrochloride(TH)were applied here as model drugs.IND-loaded single drug zein/EC/PEO nanocomposite and IND/TH-loaded dual drug zein/EC/PEO nanocomposite were successfully prepared.Electrosprayed PEO nanoparticles with good morphologies were produced with a mixed solvent system,containing acetic acid,deionized water and ethanol when PEO concentration was set at 10%.Drug-loaded electrosprayed nanoparticles,deposited on the drug-loaded electrospun zein/EC nanofibrous matrix,improved the surface wettability.The result of in vitro drug release experiments illustrated that the dissolution of IND was improved when incorporated in the electrosprayed PEO nanoparticles.The initial burst of IND and a sustained release of TH were realized according to drug release profile of the IND/TH dual drug nanocomposite.