Distribution of fibroblast growth factor-2 (FGF-2) within model excisional wounds following topical application.
OBJECTIVE
To characterise the magnitude and distribution of fibroblast growth factor-2 (FGF-2) following topical application in hypromellose gel and film formulations or a solution in an animal wound model, in order to assess the potential of this route for treatment of chronic wounds.


METHODS
Topical formulations of FGF-2 were applied to punch biopsy wounds, and FGF-2 levels within the wound measured. Each 12 mm diameter wound received 0.3 microg FGF-2 in solution, a 7% (w/w) hypromellose gel, a dried hypromellose film on Melolin-backing or a saline control. After 2, 5 or 8 h the wounds were horizontally dissected into four sections (surface granulation, subcutaneous fat, superficial muscle and deep muscle) which were then analysed for FGF-2 concentration using ELISA. Confocal microscopy was used to evaluate the distribution of FGF-2 within the wound.


RESULTS
There were significant differences in the mean FGF-2 levels with respect to formulation and time following application (P < 0.05). FGF-2 penetrated faster into tissue when formulated as a solution than as a gel or a film. There did not appear to be a significant difference between the gel and the film with respect to total concentrations achieved in the tissue, although confocal microscopy showed differences in FGF-2 distribution within the wound.


CONCLUSIONS
Delivery of FGF-2 to wounds in a solution gave the greatest increase in tissue FGF-2 concentration when measured by ELISA and visualised using confocal microscopy. Gel and film formulations prolonged the release of FGF-2 into the wound, although FGF-2 levels were not significantly different from controls when measured by ELISA. Confocal microscopy highlighted the differences in the penetration and distribution of the FGF-2 within the wound when released from different formulations.
Braund
Rhiannon
R
School of Pharmacy, University of Otago, Dunedin, New Zealand. rhiannon.braund@otago.ac.nz
Hook
Sarah M
SM
Greenhill
Nicholas
N
Medlicott
Natalie J
NJ
D000287:Administration, Topical; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D005453:Fluorescence; D005782:Gels / Q000737:chemistry; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D018613:Microscopy, Confocal; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D012996:Solutions / Q000737:chemistry; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D005782:Gels; D011994:Recombinant Proteins; D012996:Solutions; D016222:Fibroblast Growth Factor 2; D065347:Hypromellose Derivatives; D008747:Methylcellulose