Novel antibacterial nanofibrous PLLA scaffolds.
Novel antibacterial nanofibrous PLLA scaffolds.
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DOI：
10.1016/j.jconrel.2010.05.035
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发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Ma PX
中科院分区：
文献类型：
--
作者：
Feng K;Sun H;Bradley MA;Dupler EJ;Giannobile WV;Ma PX
为了在牙科、牙周和骨感染的治疗中获得较高的局部生物活性和较低的全身副作用，一个局部的和时间控制的给药系统是至关重要的。在这项研究中，开发了一种三维(3D)多孔组织工程支架，能够以受控的方式释放抗生素，从而长期抑制细菌生长。采用改进的油包水(w/o/o)乳化法，成功地将高度溶解的抗生素药物多西环素(Doxy)包合到PLGA纳米球中。然后将PLGA纳米球(NS)引入到具有良好互联大孔结构的预制纳米纤维PLLA支架中。研究了4种不同PLGA NS制剂在PLLA支架上的释药动力学。Doxy可以以局部和时间控制的方式从NS-支架中释放。Doxy的释放是由Doxy在NS外的扩散控制的，并且强烈依赖于PLGA的物理化学性质。PLGA50-6.5K、PLGA50-64K和PLGA75-113K支架可快速释放Doxy，具有较高的起爆释放量，而PLGA85-142K支架具有较低的起爆释放量，可将Doxy的释药延长至6周以上。与单独使用生理盐水相比，安装在3-D支架上的生理盐水显著减少了最初的突发释放。体外抗菌实验表明，PLGA85 NS支架对常见细菌(金黄色葡萄球菌和大肠杆菌)的生长有较长时间的抑制作用。Doxy成功地结合到3-D支架上，并从支架上控制释放，将纳米纤维支架的用途从输送生长因子等大分子扩展到输送小的亲水性药物，从而允许更广泛的应用和更复杂的组织工程策略。
In order to achieve high local bioactivity and low systemic side effects of antibiotics in the treatment of dental, periodontal and bone infections, a localized and temporally controlled delivery system is crucial. In this study, a three-dimensional (3D) porous tissue engineering scaffold was developed with the ability to release antibiotics in a controlled fashion for long-term inhibition of bacterial growth. The highly soluble antibiotic drug, Doxycycline (DOXY), was successfully incorporated into PLGA nanospheres using a modified water-in-oil-in-oil (w/o/o) emulsion method. The PLGA nanospheres (NS) were then incorporated into prefabricated nanofibrous PLLA scaffolds with a well interconnected macroporous structure. The release kinetics of DOXY from four different PLGA NS formulations on a PLLA scaffold was investigated. DOXY could be released from the NS-scaffolds in a locally and temporally controlled manner. The DOXY release is controlled by DOXY diffusion out of the NS and is strongly dependent upon the physical and chemical properties of the PLGA. While PLGA50-6.5K, PLGA50-64K, and PLGA75-113K NS-scaffolds discharge DOXY rapidly with a high initial burst release, PLGA85-142K NS-scaffold can extend the release of DOXY to longer than 6 weeks with a low initial burst release. Compared to NS alone, the NS incorporated on a 3-D scaffold had significantly reduced the initial burst release. In vitro antibacterial tests of PLGA85 NS-scaffold demonstrated its ability to inhibit common bacterial growth (S.aureus and E.coli) for a prolonged duration. The successful incorporation of DOXY onto 3-D scaffolds and its controlled release from scaffolds extends the usage of nano-fibrous scaffolds from the delivery of large molecules such as growth factors to the delivery of small hydrophilic drugs, allowing for a broader application and a more complex tissue engineering strategy.
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