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    Octaarginine functionalized nanoencapsulated system: In vitro and in vivo evaluation of bFGF loaded formulation for wound healing
    (Elsevier, 2022) Erel-Akbaba, Gulsah; Akbaba, Hasan; Keselik, Erdi; Bahceci, Selen Akyol; Senyigit, Zeynep; Temiz, Tijen Kaya
    Despite all treatment efforts, diabetic wounds are still a major health concern that needs to be solved. Growth factor-based therapeutic approaches offer promising results for wound healing therapy. However, their high sensitivity to proteolysis causes repetitive application, and associated high cost makes it necessary to develop an effective delivery system. In this study, an innovative approach for protein delivery was developed and evaluated in terms of wound healing activity. For this purpose, basic fibroblast growth factor was first encapsulated into chitosan and alginate based polymeric system. Then, a cell penetrating peptide, octaarginine, was incorporated onto the system to achieve a higher therapeutic effect. The characterization studies were performed, and the optimal nanoparticle system was dispersed in hydroxypropyl methylcellulose for providing skin application. The in vitro and in vivo efficiency of the system was also evaluated. According to the results, the obtained gel formulation is safe for the applied doses up to 150 mg/mL and significantly promotes fibroblast cell migration in 48 h. Furthermore, in vivo studies revealed that the diabetic wound healing efficiency of basic fibroblast growth factor nanoencapsulated gel system significantly accelerates wound healing. Moreover, by functionalizing this system with octaarginine, epithelization, granulation of tissue formation, and treatment efficacy were promoted. In conclusion, this work designs a suitable cell penetrating peptide functionalized nanoencapsulated system for growth factor delivery, which provides a promising therapeutic potential for hard-to-heal skin lesions, particu-larly diabetic wounds.