Department of Pharmaceutical Chemistry, University of Pavia, Viale Taramelli 12, Pavia, Italy.
J Pharm Pharmacol. 2011 Feb;63(2):189-98. doi: 10.1111/j.2042-7158.2010.01208.x. Epub 2010 Nov 18.
Growth factors contained in platelet α-granules initiate and modulate tissue repair and are proposed for the treatment of soft and hard-tissue surgical conditions and in the management of non-healing wounds. Platelet lysate is a hemoderivative obtained from platelet-rich plasma and is capable of releasing a pool of growth factors. Many medical and surgical techniques have been proposed for the treatment of corneal lesions; management of these conditions remains problematic and healing with standard protocols is unattainable. The aim of this study was to develop formulations suitable for prolonging the contact of platelet lysate with the damaged cornea for the time necessary to exert a therapeutic effect.
Two vehicles, one based on polyacrylic acid and one based on chitosan, were autoclaved and loaded with platelet lysate and the resultant formulations were characterized for rheology, mucoadhesion, vehicle compatibility and stability. The proliferation effect was tested on two cell culture types (rabbit corneal epithelial cells and fibroblasts). An in-vitro wound-healing test was performed on fibroblasts. In both cases the formulations were compared with platelet lysate diluted with saline at the same concentration.
Both formulations maintained the rheological and mucoadhesive properties of the vehicles and the proliferative activity of platelet lysate. The chitosan formulation was able to significantly enhance epithelial cell growth even after storage of up to 2 weeks (in-use conditions), while the polyacrylic acid formulation was less efficient, probably due to the characteristics of the cell model used.
The in-vitro wound-healing test performed on fibroblasts confirmed the differences between the two vehicles. The effect induced by the platelet lysate and chitosan formulation was faster than that of the polyacrylic acid formulation and complete in-vitro wound repair was achieved within 48 h.
血小板α-颗粒中包含的生长因子启动并调节组织修复,可用于治疗软组织和硬组织手术状况,并管理难愈性伤口。血小板裂解液是从富含血小板的血浆中获得的血液衍生物,能够释放出大量的生长因子。已经提出了许多用于治疗角膜病变的医疗和外科技术;但这些情况下的管理仍然存在问题,且按照标准方案无法实现愈合。本研究旨在开发适合延长血小板裂解液与受损角膜接触时间的制剂,以发挥治疗效果。
两种载体,一种基于聚丙烯酸,另一种基于壳聚糖,经高压灭菌并加载血小板裂解液,对所得制剂的流变性、黏膜附着力、载体相容性和稳定性进行了表征。在两种细胞培养类型(兔角膜上皮细胞和成纤维细胞)上测试了增殖效果。在成纤维细胞上进行了体外伤口愈合试验。在这两种情况下,将制剂与用生理盐水稀释至相同浓度的血小板裂解液进行比较。
两种制剂均保持了载体的流变学和黏膜附着力特性以及血小板裂解液的增殖活性。壳聚糖制剂即使在长达 2 周的储存后(使用条件下),仍能显著增强上皮细胞的生长,而聚丙烯酸制剂的效果较差,这可能是由于所用细胞模型的特性所致。
在成纤维细胞上进行的体外伤口愈合试验证实了两种载体之间的差异。由血小板裂解液和壳聚糖制剂诱导的作用比聚丙烯酸制剂更快,在 48 小时内即可实现完全的体外伤口修复。