On The Fabrication And Sustained-release Performance Of Emulsion Electrospun Polycaprolactone Fibers Loaded With Tetracycline Hydrochloride

Polymer nanofibers have been extensively used as biomaterials for diverse biomedical applications, due to the large surface area to volume ratio, high porosity and so on, which can simulate the structure and biological function of the extracellular matrix. Electrospinning is a simple and powerful technology to fabricate nanofibers. Therefore, biodegradable polymer materials can be prepared by the electrospinning method to be drug-loaded scaffold, which has broad application prospects in the field of tissue engineering.For water-soluble drugs, drugs can be encapsulated into the fibers by emulsion electrospinning. Current researches have successfully embedded the protein, abtibiotics, nucleic acid and anti-cancer drugs by emulsion electrospinning. However, it’s still a challenge to increase the drug loading capability and control the drug release behavior. There are few studies on the perspective of the emulsion system itself and carrying on systematic research about formation of emulsion and fibers and drug release profiles. Based on the above problems, polycaprolactone(PCL) fibers containing water-soluble drug, tetracycline hydrochloride(Tet) were prepared by emulsion electrospinning, this paper addresses the following aspects:(1) Establishment of stable emulsion system. By analyzing the formation mechanism and influence factors of emulsion, two different ways of emulsification were compared to select the appropriate emulsification method. Then, different concentrations of emulsifier(Span80) were prepared for emulsions. The stability of emulsion was characterized by the time duration when the emulsion lamination appeared due to demulsification. The morphological features of dispersed droplets were observed and photographed by an optical microscope.(2) Fabrication and characterization of core-sheath structure PCL/Tet nanofibers. By changing polymer concentration, drug concentration and emulsifier concentration to prepare PCL/Tet nanofiber samples. The morphology of the emulsion electrospun nanofibers was observed with a scanning electron microscope(SEM). ImageJ, Origin and SPSS softwares were also used to analyze the effects of main factors above on the diameter distribution of nanofibers. Drug distribution was observed from the fluorescence images by a laser scanning confocal microscope(LSCM). Core-sheath structure was observed by a transmission electron microscope(TEM). Attention was focused on the influence of emulsifier concentrations on formation of core-sheath structure and fiber hydrophilicity.(3) Study of drug loading and encapsulation efficiency and analysis of the influence of emulsifier concentration on drug loading capability of PCL/Tet fibers. By plotting cumulative Tet release curve in vitro test, the influence of emulsifier concentration on drug release behavior was analyzed.The results showed that stable emulsion could be prepared when concentration of Span80 kept in the range of 0.4% to 4.0%. The increase of Span80 facilitated the stability and uniformity of the dispersed droplets. The dispersed droplet size decreased with the increase of Span80 and it reached a plateau of about(1.07 ± 0.14) μm at the concentration of 2.0%. Fibers with 8% polymer concentration were more uniform with minimum diameter discrete degree. With the increase of Span80 concentration ranging from 0 to 4.0%, the spinnability of the spinning solution was improved and beads on the fiber surface were decreased. 0.5% was the lowest Span80 concentration to fabricate smooth fibers. When Span80 concentration increased from 0.5% to 1.0%, the diameter of fibers increased. With Span80 increased continuously to 4.0%, fibers were conglutinated which resulted in the increase of fiber diameter and irregularity. Fibers with Span80 concentration of 0.5%、1.0% and 2.0% had integral core-sheath structure and drugs were distributed in the core region of the fibers. Moreover, with the increase of Span80, the thickness of sheath layer had a tendency to become larger which leaded to the decrease of drug content embedded in the core. With the Span80 concentration increasing from 0 to 2.0%, hydrophilicity of fibers improved. Fibers without Span80 showed fairly low drug loading and encapsulation efficiency. Fibers with Span80 in the range of 0.5% to 2.0%, drug loading and encapsulation efficiency of fibers decreased with the increase of Span80. Compared with the fibers with Span80, fibers without Span80 showed a faster drug release. Fibers with Span80 concentration of 0.5%, 1.0% and 2.0% had a higher drug loading capability and longer effective release lifetime. The drug release profiles of core-sheath structure fibers conformed to Q = ktn Peppas model, in which 0.45< n< 0.89. It meant that drug release mechanism was the cooperation of diffusion and matrix erosion.