Title
Development of Topical Delivery Systems for Flightless Neutralizing Antibody
Author
Hanif Haidari, Qian Zhang, Elizabeth Melville, Zlatko Kopecki, Yunmei Song, Allison J. Cowin, Sanjay Garg
Year
2017
Journal
Journal of Pharmaceutical Sciences
Abstract
Flightless I (Flii) is an actin remodelling protein important for cytoskeletal regulation and cellular processes including migration, proliferation and adhesion. Previous studies have clearly identified Flii as a novel therapeutical target for improved wound repair and have demonstrated Flii regulation using Flii neutralizing antibodies (FnAb) in different models of wound healing in vivo. Here we describe the development of an optimised topical delivery system that can neutralize Flii activity in the epidermis. Topical delivery of FnAb is an attractive approach as it provides a convenient application, sustained release, localised effect and reduced dosage. Three successful formulations were developed, and their physical and chemical stability examined. The in vitro release revealed prolonged and sustained release of FnAb in all of the tested formulations. Additionally, penetration studies using intact porcine skin showed that FnAb penetrated the epidermis and upper papillary dermis. The penetrated FnAb significantly reduced Flii expression compared to dosed matched IgG controls. This study has successfully developed a topical delivery system for FnAb that could serve as a potential platform for future localised wound treatments.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Antibodies, Thermal stability, Biochemistry