Biodegradable Electrospun Ultrafine Fibers

Electrospinning technology is a simple and cost-effective method to prepare ultrafine fibers. Within the last decade, significant progress was achieved on its theoretical and experimental studies. The diameter of electrospun fibers is usually 1-3 orders smaller than that of common fibers prepared by conventional spinning techniques, thus, promising prospective was expected on the applications of the electrospun fibers in reinforced composites, filtration, protective clothing, optical and electrical devices and especially biomedical fields such as tissue engineering scaffolds, drug delivery and controlled release, wound dressing and so on, which are attracting more and more attention in the world. However, due to the complexity of the electrospinning process and the diversity of the electrospinning parameters, one of the challenges in electrospinning is the preparation of the electrospun fibers with narrow diameter distribution. Moreover, the application of electrospun fibers in drug delivery and controlled release was developed only within the last two or three years, and so some problems still need to be solved such as drug burst release. In order to solve the above problems, this thesis systematically studied the influences of solvent system, surfactant, electrospinning flow rate, diameter of the spinning outlet, environmental temperature and atmosphere flowing on the electropinning process and the morphology of electrospun fibers by using PLA, PLGA (80/20) and PCL as fiber-forming materials, and analyzed the characteristics of the electrospun fibers obtained. Based on these results, we further studied the enzymatic degradation behaviors of PLLA and PCL electrospun ultrafine fibers. Great progress was achieved in the encapsulation of rifampin, paclitaxel and doxorubicin by PLLA fibers, and constant drug release profiles were obtained. The main results were listed as follows: 1. PLA,PCL and PLGA(80/20) electrospun ultrafine fibers were prepared by using chloroform, chloroform/acetone, 1,2-dichloromethane and chloroform/ 1,2-dichloromethane as solvent systems. The optimal solvent system was chloroform/acetone mixture with 1:1 volume ratio, and the electropinning process and the morphology of the fibers were improved greatly. The addition of cationic surfactant triethyl benzyl ammonium chloride (TEBAC) and anionic surfactant sodium dodecyl sulphate (SDS) could also significantly improve the electropinning process and the morphology of the fibers, while the improvements achieved by the nonionic surfactant aliphatic PPO-PEO ether (AEO10) was less significant. More pressure applied to the solution and larger spinning outlet resulted in higher solution flow rate, and adhesive fibers might be obtained in extreme case. In addition, coiled and entangled fibers were obtained due to the air circulation around the spinning site. 2. The apparent porosity of PLA, PCL and PLGA(80/20) electrospun fibers were very high, being 89 %, 68 % and 80 %, repectively, and so the mechanical properties of the electrospun fibers were not as good as those of the corresponding films. 3. Although the electrospinning process results in alignment and orientation of the polymer chains within the fiber to a great extent, crystalline structure can not be developed very well due to the quick solidification of the fiber. Thus, crystallinity of the PCL fiber mats was lower than that of the corresponding film according to DSC and WXAD results. As for the PLLA fiber mats, DSC analyses revealed that the crystallinity in the fiber mats was enhanced due to the movement of the polymer chains during the heating process. 4. Proteinase K carried a little positive charges in Tris-HCl buffer, and so anionic surfactants could adsorb proteinase K, while cationic surfactants repulsed it. Thus, the enzymatic degradation rate of PLLA fiber mats containing 5 wt% SDS was faster thanthat of PLLA fibers containing 5 wt% TEBAC. Although high orientation may lie in PLLA chains, PLLA fibers were in noncrystalline state during the whole degradation process. No obvious crystallization occurred. 5. To the contrary, lipase PS was negative in the phosphate buffer (PBS), and so the cationic surfactant TEBAC could adsorb lipase PS, which resulted in faster degradation rate of PCL fiber mats containing 5 wt% TEBAC, while the repulsion effect of the anionic surfactant SDS prohibited PCL fibers from degradation. According to DSC and WAXD results, the crystallinity of PCL fibers containing 5 wt% TEBAC was enhanced during the degradation, probably due to the following two reasons: firstly, the degradation of PCL fibers by lipase PS preferentially occurred at the amorphous domains; and secondly, the degradation temperature (37 ℃) was above the Tg temperature of PCL and near the Tc of PCL, and thus the movements of the aligned and oriented PCL chains in the fibers caused the formation of new crystals and the increase in crystallinity. 6. The improvements in the electrospinning process and in the diameter distribution of the electrospun fibers could also be accomplished by adding certain amounts of rifampin, paclitaxel and doxorubicin. 7. Both the SEM photographs and the results of the controlled drug release experiments showed perfect encapsulation of the model drug--rifampin and the anticancer drug--paclitaxel inside the PLLA fibers. The release behavior of rifampin-PLLA fibers and paclitaxel-PLLA fibers followed zero-order kinetics, and no burst release occurred. The degradation of PLLA fibers was the main reason of the release. Such results were firstly reported in the world, and essential progress was made in the electrospun fibers drug formulation. 8. The drugs'solubility in the solvent system and compatibility with the polymer materials will directly influence the encapsulation effect. Generally, lipophilic drugs can be encapsulated inside the lipophilic polymer fibers. So the hydrophilic drug--doxorubicin hydrochloride was difficult to be encapsulated inside the lipophilicPLLA fibers, and many doxorubicin hydrochloride particles were observed outside or on the surface of fibers. Correspondingly, serious burst release was observed, which mainly resulted from the dissolution or diffusion of doxorubicin hydrochloride outside or on the surface of fibers. However, when hydrophilic doxorubicin hydrochloride was converted into lipophilic doxorubicin, the better encapsulation effect was achieved, its enzymatic release was constant, and no burst release occurred. 9. The perfect encapsulation of rifampin inside PLGA (80/20) fibers can also be accomplished as revealed by SEM photographs. The release rate of rifampin-PLGA (80/20) fibers in PBS was increased with increasing rifampin content. The more rifampin content, the quicker the rifampin release rate. At the initial period, the diffusion of rifampin was the main reason of release, and at the later period, both the diffusion of rifampin and the degradation of PLGA (80/20) fibers contributed to the release. Properly increasing rifampin content (30 wt%) resulted in a constant release behavior. 10. The increase of the concentration of TEBAC or SDS in PBS accelerated the release rate of rifampin-PLGA (80/20) fibers to a certain extent. The addition of the surfactants could decrease the surface tension of PBS, and so increased the soaking ability of water to the PLGA (80/20) fibers, thus accelerating the diffusion of rifampin.