Development of Topical Delivery Systems for Flightless Neutralizing Antibody.

Abstract:

: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.

journal_name

J Pharm Sci

authors

Haidari H,Zhang Q,Melville E,Kopecki Z,Song Y,Cowin AJ,Garg S

doi

10.1016/j.xphs.2017.03.012

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

1795-1804

issue

7

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(17)30169-7

journal_volume

106

pub_type

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