以天然高分子包覆聚氧化乙烯之同軸電紡奈米纖維製備與特性探討

Abstract

本研究使用同軸靜電紡絲法製備具有核/殼層結構之奈米纖維，在材料的選擇上，以合成高分子聚氧化乙烯(PEO)作為核層材料，以提供整體膜材的機械強度，並利用其易於電紡的性質帶出殼層溶液，形成同軸纖維；殼層材料則選用天然高分子幾丁聚糖(chitosan)和動物明膠(gelatin)，以提高膜材的生物相容性及抗菌性，並形成質傳阻力，延緩核層中的藥物釋放速率，以期作為可攜帶藥物的生醫材料。 在同軸纖維的製備上，本研究配製了不同高分子濃度和不同溶劑組成之核/殼層溶液，搭配不同電壓及流量比進行同軸電紡，藉由溶液性質分析及SEM觀察電紡纖維型態，來探討溶液性質和製程參數對於電紡結果的影響。在殼層溶液方面，提高溶劑(醋酸水溶液)中的醋酸含量可以有效降低溶液的表面張力和導電度，是能否電紡出纖維的關鍵，溶質的濃度則主要影響了溶液的黏度，也須控制在一定範圍內，實驗結果顯示當溶劑中醋酸濃度為50 wt%，溶質幾丁聚醣和動物明膠的濃度皆為8 wt%時，能夠製備出最均勻的纖維。在核層溶液的搭配上，溶質PEO的濃度會大幅影響溶液黏度，而溶劑的選擇則會影響到電紡時針尖的穩定性和濕度耐受性，以純水作為溶劑針尖溶液的噴出容易不穩定，溶劑改為醋酸水溶液可以穩定針尖的噴出，但對於濕度耐受度不佳，而溶劑選用乙醇水溶液則可以穩定地電紡，同時具有較高的濕度耐受力。實驗結果顯示以6 wt% 的PEO溶解於50 wt%乙醇水溶液作為核層溶液，搭配上述殼層溶液，並在施加電壓為25 kV、收集距離為24公分下能夠最穩定地電紡，並形成均勻的同軸奈米纖維。 確定溶液組成和操作參數後，以TEM進行結構確認，證實纖維確實具有同軸結構，且核/殼層流量比為0.30 : 0.30 mL/h時可以得到最佳同軸型態，而由SEM圖則可以計算出在此流量比狀況下纖維之直徑約為809.93 ± 220.88 nm；紅外線吸收光譜的測試結果也證明核/殼層材料同時存在於膜材中。之後，將纖維膜以戊二醛(glutaraldehyde)進行不同時間的交聯反應，再測定其抗拉強度，結果顯示交聯反應可以提高膜材的抗拉強度至1.78 ± 0.07 MPa，且本系統最佳的交聯時間為1小時。最後將膜材作為藥物載體，分別將親水性小分子 — 茶鹼，和疏水性小分子 — 苯左卡因置於核層再進行藥物釋放測定，結果顯示同軸纖維膜雖仍有藥物快速大量釋放的現象，但與純PEO纖維膜相比已改善許多。總結來說，本實驗製備之同軸奈米纖維膜材不但具有較高的抗拉強度和良好的細胞相容性，更具有延緩藥物釋放的功能，是非常具有潛力之生醫材料。

In this research, coaxial nanofibers with core/shell structures were fabricated by coaxial electrospinning. Polyethylene oxide (PEO) was chosen as core material to provide proper mechanical strength and to assist the electrospinnability of shell materials, namely, chitosan and gelatin. Both of biopolymer were chosen to enhance the biocompatibility of nanofibers and to provide the antibacterial effect. The shell layer could yield mass transfer resistance and thus slowed down the drug release from the core layer. The nanofiber mats could act as drug-carrying biomaterials. Various core/shell solutions with different concentrations and compositions of solutes and solvents were prepared and electrospun into coaxial nanofibers using different electrospinning conditions such as applied voltages, flow rates and collecting distances. The effects of solution properties and electrospinning conditions on the morphology of coaxial nanofibers were investigated. The concentration of acetic acid in the shell solution was crucial. As the concentration of acetic acid increased, the surface tension and conductivity of solution decreased, thus causing the morphology of nanofibers to become more uniform. The concentration of natural polymer in the shell solution, which would affect the viscosity of the solution, should be also in a proper range. Results revealed that the use of 50 wt% acetic acid aqueous solution as the solvent, 8 wt% chitosan and 8 wt% gelatin as solutes could result in the most uniform nanofibers. As for core solution, its viscosity was significantly affected by the concentration of the solute PEO, while the composition of solvent affected the stability of electrospinning jet and electrospinnability at a higher humidity. When the solvent was pure water, electrospinning jet was unstable. When the solvent was aqueous acetic acid solution, the jet was stable but the electrospinnability at a higher humidity was poor. When the solvent was aqueous ethanol solution, the jet was stable and the electrospinnability at a higher humidity was satisfactory. Hence the most promising core solution contained 6 wt% PEO as the solute and 50 wt% ethanol aqueous solution as the solvent. We also found that the optimum coaxial electrospinning should be carried out under 25 kV applied voltage and 24 cm collecting distance for the best result. The core/shell structure was then confirmed by TEM images, and it was found that when the solution flow rate ratio was 0.30:0.30 mL/h (core:shell), the coaxial structure was the best. SEM images indicated that the nanofiber diameters were in the range of 809.93 ± 220.88 nm when the flow rate is 0.30:0.30 mL/h (core:shell). The results of FT-IR analysis confirmed that both core and shell materials were present in the coaxial nanofibers. To enhance the tensile strength, the coaxial nanofibers mats were crosslinked by glutaradehyde for different times. The tensile strength of coaxial nanofiber mats was enhanced to 1.78 ± 0.07 MPa with a crosslinking time of 1 hour. Finally, the coaxial nanofiber mat was utilized as a drug carrier. Theophylline (a hydrophilic drug) and benzocaine (a hydrophobic drug) were added to the core solution. The drug release curves indicated that the core/shell structure could significantly reduce the initial burst of drug release. It is believed that the prepared coaxial nanofiber mat, which has good tensile strength and improved drug release characteristics, is a promising biomaterial.