Picheth Guilherme Fadel, Sierakowski Maria Rita, Woehl Marco Aurelio, Ono Lucy, Cofré Axel Rulf, Vanin Luana Pasetti, Pontarolo Roberto, De Freitas Rilton Alves
Biopol, Chemistry Department, Federal University of Paraná, Curitiba 81531-980, Paraná, Brazil; CEB, Pharmacy Department, Federal University of Paraná, Curitiba 80210-170, Paraná, Brazi.
Biopol, Chemistry Department, Federal University of Paraná, Curitiba 81531-980, Paraná, Brazil.
J Pharm Sci. 2014 Dec;103(12):3958-3965. doi: 10.1002/jps.24205. Epub 2014 Oct 10.
A novel wound-dressing biodevice, sensitive to lysozyme, an enzyme commonly found at infected skin wounds, was assembled by the layer-by-layer deposition of nanopolymeric chitosan and alginate films onto oxidized bacterial cellulose membranes incorporated with epidermal growth factor (EGF). Distinct EGF release profiles were obtained according to specific stimuli caused by infection. In in vitro conditions simulating noninfected wounds, the EGF rate and burst release effect were reduced by three deposited layers (Mt /M∞ of 0.25 at 3 h) in a process dependent on the porosity of the compact chitosan-alginate complex. The importance of the organized structure was revealed when an infected wound was simulated by adding lysozyme to the release medium, thus inducing the formation of a loosely polyelectrolyte architecture that caused rapid EGF diffusion (Mt /M∞ of 0.75 at 30 min). The results indicate that the nanopolymeric layers were capable of slowly releasing EGF as required for normal wound repair and rapidly undergoing architectural transitions that allow the diffusion of massive amounts of drug to enhance the process of re-epithelialization. In summary, the proposed system comprises the roles of both wound dressing and local delivery mechanism to recognize infections and respond with a burst of EGF release.
一种新型的伤口敷料生物装置,对溶菌酶敏感,溶菌酶是一种常见于感染皮肤伤口的酶,它通过将纳米聚合壳聚糖和藻酸盐薄膜逐层沉积到结合了表皮生长因子(EGF)的氧化细菌纤维素膜上组装而成。根据感染引起的特定刺激,获得了不同的EGF释放曲线。在模拟未感染伤口的体外条件下,EGF的释放速率和突释效应在依赖紧密壳聚糖 - 藻酸盐复合物孔隙率的过程中,因三层沉积而降低(3小时时Mt /M∞为0.25)。当通过向释放介质中添加溶菌酶来模拟感染伤口时,揭示了组织结构的重要性,从而诱导形成松散的聚电解质结构,导致EGF快速扩散(30分钟时Mt /M∞为0.75)。结果表明,纳米聚合物层能够根据正常伤口修复的需要缓慢释放EGF,并迅速经历结构转变,从而允许大量药物扩散以增强重新上皮化过程。总之,所提出的系统兼具伤口敷料和局部递送机制的作用,能够识别感染并通过EGF的突释做出反应。