Development of Topical Delivery Systems for Flightless Neutralizing Antibody.
Flightless I (Flii) is an actin remodeling 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 optimized 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, localized 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 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 localized wound treatments.
Centre for Pharmaceutical Innovation and Development, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
Hanif
H
Haidari
Centre for Pharmaceutical Innovation and Development, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
Qian
Q
Zhang
Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.
Elizabeth
E
Melville
Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.
Zlatko
Z
Kopecki
Centre for Pharmaceutical Innovation and Development, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
Yunmei
Y
Song
Regenerative Medicine, Future Industries Institute, University of South Australia, Adelaide, South Australia, Australia.
Allison J
AJ
Cowin
Centre for Pharmaceutical Innovation and Development, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia. Electronic address: sanjay.garg@unisa.edu.au.
Sanjay
S
Garg
D000287:Administration, Topical; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D051379:Mice; D008840:Microfilament Proteins; D012869:Skin Absorption; D013552:Swine; D015534:Trans-Activators
D057134:Antibodies, Neutralizing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D003692:Delayed-Action Preparations; C000609263:FlII protein, mouse; D008840:Microfilament Proteins; D015534:Trans-Activators
in vitro models; permeability; protein delivery; transdermal drug delivery; wound healing