Acidic fibroblast growth factor: evaluation of topical formulations in a diabetic mouse wound healing model.
The efficacy of topical formulations of acidic fibroblast growth factor (aFGF) in healing of full-thickness wounds has been studied in a diabetic db+/db+ mouse model. The effect of several formulation variables, dose, and application frequency was examined. It was found that wound healing in diabetic animals treated with aFGF or placebo was slower than in their nondiabetic littermates. The availability of aFGF from the viscous vehicle employed in this study (1% hydroxyethyl cellulose) was demonstrated in vitro using diffusion cells. The viscous formulation of aFGF was equally effective in wound healing as a nonviscous formulation in phosphate-buffered saline. A formulation containing heparin (necessary for full biological and conformational stability of aFGF) at a mass ratio of 3:1 to aFGF was more efficacious than formulations with lower heparin: aFGF ratios. Wounds treated with three doses of 3.0 micrograms/cm2 aFGF healed faster than those treated with a single dose of 3.0 micrograms/cm2 aFGF. Three applications of 3.0 or 0.6 microgram/cm2 a FGF were equally effective in accelerating wound healing.
Matuszewska
B
B
Department of Pharmaceutical Research and Development, Merck Research Laboratories, West Point, Pennsylvania 19486.
Keogan
M
M
Fisher
D M
DM
Soper
K A
KA
Hoe
C M
CM
Huber
A C
AC
Bondi
J V
JV
D000287:Administration, Topical; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D005079:Excipients; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006493:Heparin / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D014945:Wound Healing / Q000187:drug effects*
D001786:Blood Glucose; D005079:Excipients; D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D002482:Cellulose; C002283:hydroxyethylcellulose; D006493:Heparin