Immunohaematology and Transfusion Service, Apheresis And Cell Therapy Unit, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
AAPS PharmSciTech. 2011 Sep;12(3):893-9. doi: 10.1208/s12249-011-9649-3. Epub 2011 Jul 6.
Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2-8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.
目前,尚无针对移植物抗宿主病(GvHD)所致口腔黏膜炎(OM)的最佳治疗方法。血小板衍生生长因子(PDGFs)具有很强的组织修复能力,可能在修复黏膜屏障方面发挥作用。本研究旨在开发一种黏附制剂,以将富含血小板的裂解物施用于口腔,延长血小板裂解物与口腔黏膜的接触时间。对黏附制剂的体外特性(PDGF-AB 浓度、黏附特性、细胞毒性、成纤维细胞增殖、伤口愈合)进行了表征。此外,对 7 例接受其他治疗方法无效的 GvHD 伴 OM 患者进行了初步临床研究,以评估其可行性、安全性和疗效。GVPL(与富含血小板的裂解物混合的黏附凝胶载体)具有良好的黏附特性;此外,它在体外对成纤维细胞具有良好的生物相容性,能够增强成纤维细胞增殖和伤口愈合,并在 2-8°C 储存长达 14 天后保持疗效。在体内,5 例患者的临床反应良好至完全,1 例患者反应一般,1 例患者无反应。体外结果表明,GVPL 具有最佳的黏附性和愈合增强特性,且随着时间的推移(长达 14 天)保持稳定;初步临床结果表明,富含血小板的裂解物的黏附制剂经口腔应用是可行、安全、耐受良好且有效的。需要进行更大规模的对照随机研究。