Study On Structure And Performance Regulation Of Self-adhesive Electrospun Membranes For Topical Patch

Transdermal drug delivery systems（TDDS）have attained great attention due to their advantages of avoiding the first-pass effect in the liver,maintaining a constant blood drug concentration,easy administration and good revocability.Among them,topical patches are widely used because of their simple structure.However,their key components（matrix）for transdermal administration are insufficient in drug release and air permeability.To overcome the above disadvantages,various electrospun membranes have been developed.However,most electrospun membranes do not have adhesion and are difficult to apply directly to the surface,which affects the efficiency of transdermal drug delivery.Since polystyrene thermoplastic elastomer based pressure-sensitive adhesives have good biocompatibility,controllable adhesion and high drug loading,this paper develops a self-adhesive electrospun membranes suitable for transdermal drug delivery and systematically studies how to regulate the system structure and properties via C5 resin,poly（styrene isoprene phenylethylene）（SIS）or Poly（styrene-b-（ethylene-co-butene）-b-styrene）（SEBS）,model drugs,and drug loading.The main contents are as follows:（1）Taking synthetic capsaicin as the model drug,C5 petroleum resin and SIS as the matrix,and using C5 petroleum resin to control the structure of the electrospinning fiber membrane patch.The effects of matrix composition on the structure,adhesion properties and air permeability of drug-loaded SIS/C5 electrospinning membranes and the regulation rules were studied.The results showed that with the increase of C5 resin content,the cross-linked structure of the fiber membrane increased,the water vapor permeability showed a decreasing trend as a whole,but remained at about 6.5×10^-3 g/（h·cm²）,the initial viscosity and 180°peel strength increase gradually.Among them,when the ratio of SIS/C5 is 2:1,the initial viscosity and 180°peel strength of the spinning fiber matrix are 0.64 N/cm² and 0.2 k N/m,respectively,which meet the requirements of human skin.（2）Using SIS/C5（2:1）electrospinning membrane as a platform,drug-loaded fiber membrane patches with different loadings of synthetic capsaicin（2%,4%,6%,8%）were prepared.The effects of drug loading on the structure,adhesive properties,air permeability and drug release properties of the patch and the regulation rules were studied.The results showed that the synthetic capsaicin existed in the matrix in an amorphous state without crystal precipitation;the fiber membrane showed a good cross-linked structure.The loading of the drug is beneficial to improve the water vapor permeability of the spun film patch;When the drug loading was 0-8%（mass fraction）,the initial adhesion of the drug-loaded spinning film was0.6-0.8 N/cm²,the 180°peel strength is maintained at 0.2-0.3 k N/m,the retention viscosity was greater than 7 days,and there was no residue during the peel.The drug release in vitro showed the characteristics of sustained release,and the 24-hour cumulative drug release rate of the spun films with different drug loadings was greater than 50%.Compared with the commercially available capsaicin patches,it showed better adhesion properties and air permeability.（3）Using 1,4-dichloromethoxybutane（BCMB）as chloromethylation reagent,SEBS with different degree of chloromethylation were synthesized（CMSEBS）,and then polyethylene glycol monomethyl ether（MPEG）was grafted to synthesize branched polymer SEBS-g-MPEG with controllable content of MPEG.The effects of solvent,spinning solution concentration,spinning voltage and working distance on the morphology of electrospun fibers were investigated.The results showed that,the degree of chloromethylation increased with the increase of the amount of BCMB.The prepared SEBS-g-MPEG is well dissolved in mixed solvent tetrahydrofuran,acetone and toluene.When the concentration of the spinning solution is 10%,the spinning voltage is 18 k V,and the working distance is 20 cm,the electrospun fibers have no beads,the surface is smooth,and the fiber diameter is uniform,which is suitable for drug loading.