Rahmani-Neishaboor Elham, Jackson John, Burt Helen, Ghahary Aziz
BC Professional Fire Fighters' Burn & Wound Healing Research Lab. Jack Bell Research Center, 2660 Oak St., Vancouver, B.C. V6H 3Z6, Canada.
Pharm Res. 2009 Aug;26(8):2002-14. doi: 10.1007/s11095-009-9916-0. Epub 2009 Jun 17.
Stratifin is a potent anti-fibrogenic factor that stimulates the expression of matrix metalloproteinase-1 (MMP-1) in dermal fibroblasts. The propose of this work was to develop a controlled release delivery system for stratifin that can be applied at the time of wound closure to release stratifin and stimulate the expression of MMP-1 in a sustained manner over the late stages of wound healing (after 3 days).
Stratifin was complexed to chitosan particles, which were then encapsulated in PLGA microspheres and blended into crosslinked hyaluronic acid films. In vitro release was assessed using fluorescent-tagged stratifin, cytotoxicity by MTT assay and bioactivity by measuring the levels of MMP-1 expression in cultured fibroblasts.
The release of stratifin was delayed for 3 days and then controlled for 30 days so that 60% of the total stratifin loaded was released. The released protein significantly stimulated the expression of MMP-1 in cultured fibroblasts without compromising cell viability. By complexing to chitosan, the initial burst release was reduced, so that only 5% of stratifin was released in 3 days.
This stratifin delivery system has the potential to be used as an anti-fibrogenic factor-associated wound insert for improving post-surgical scarring in closed wound.
层粘连蛋白是一种强效抗纤维化因子,可刺激真皮成纤维细胞中基质金属蛋白酶-1(MMP-1)的表达。本研究的目的是开发一种层粘连蛋白控释递送系统,该系统可在伤口闭合时应用,以释放层粘连蛋白并在伤口愈合后期(3天后)持续刺激MMP-1的表达。
将层粘连蛋白与壳聚糖颗粒复合,然后将其包裹在聚乳酸-羟基乙酸共聚物(PLGA)微球中,并混入交联透明质酸膜中。使用荧光标记的层粘连蛋白评估体外释放,通过MTT法评估细胞毒性,并通过测量培养的成纤维细胞中MMP-1表达水平评估生物活性。
层粘连蛋白的释放延迟3天,然后持续30天,使得加载的层粘连蛋白总量的60%被释放。释放的蛋白显著刺激培养的成纤维细胞中MMP-1的表达,而不影响细胞活力。通过与壳聚糖复合,减少了初始突释,使得3天内仅5%的层粘连蛋白被释放。
这种层粘连蛋白递送系统有潜力用作抗纤维化因子相关的伤口植入物,以改善闭合伤口的术后瘢痕形成。