In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions

Leah Benington; Jingxin Mo; Mingxin Li; Gunesh Rajan; Cornelia Locher; Lee Yong Lim

doi:10.3390/ph17020247

In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions

Pharmaceuticals (Basel). 2024 Feb 14;17(2):247. doi: 10.3390/ph17020247.

Authors

Leah Benington¹, Jingxin Mo^{2

3}, Mingxin Li^{2

4}, Gunesh Rajan^{5

6}, Cornelia Locher¹, Lee Yong Lim¹

Affiliations

¹ Division of Pharmacy, School of Allied Health, University of Western Australia, Perth, WA 6009, Australia.
² Neuroscience Laboratory, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
³ Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Department of Pharmacy, Tangshan Central Hospital, Tangshan 063000, China.
⁵ Otolaryngology, Head & Neck Surgery, Division of Surgery, Medical School, University of Western Australia, Perth, WA 6009, Australia.
⁶ Department of Otolaryngology, Head & Neck Surgery, Luzerner Kantonsspital, 6000 Luzern, Switzerland.

Abstract

Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP.

Keywords: basic fibroblast growth factor; fibroblast growth factor 2; processing stability; stabilisation; thermal stability.

Grants and funding

This research received funding from the University of Western Australia and the Guilin Medical University. L.B. was the recipient of an Australian Government Research Training Program (RTP) scholarship.