Growth factor mediated cosmeceuticals and use thereof to enhance skin quality

Abstract

It has been discovered that vascular endothelial growth factor (“VEGF”) promotes migration of activated (but not differentiating) keratinocytes to skin. This growth factor specifically increases migration of keratinocytes of the “wounded skin” phenotype but does not have significant effects upon differentiated keratinocytes. It also increases collagen deposition and reduces wrinkles, enhances skin quality, and increases skin thickness to normal levels in individuals where skin has thinned due to age or disorder such as diabetes. It is particularly well suited for use as cosmeceuticals when applied in purified form and in known amounts. The data presented in the examples demonstrate efficacy and specificity of VEGF in enhancing migration of normal human keratinocytes as well as formation of new granulation tissue including collagen formation. VEGF induces keratinocyte and fibroblast migration, formation of new tissue, and not only induces deposition of collagen but improves alignment of the collagen fibers. Accordingly, this growth factor is highly suitable for use as a cosmeceutical, especially for skin resurfacing and reduction in wrinkles.

1 . A method of treating skin to enhance skin quality comprising administering topically or locally to the skin an effective amount of a composition wherein the active ingredient consists of VEGF. 
     
     
         2 . The method of  claim 1  comprising to the surface of the skin to be treated a composition consisting of VEGF or nucleic acid molecules expressing VEGF in a formulation for topical application to the skin. 
     
     
         3 . The method of  claim 1  comprising administering by intradermal or subcutaneous injection at or near the skin to be treated a composition consisting of VEGF or nucleic acid molecules expressing VEGF in a pharmaceutically acceptable carrier for injection. 
     
     
         4 . The method of  claim 1  wherein the composition comprises a sustained or controlled release formulation providing VEGF at the site to be treated for between one and 10 days. 
     
     
         5 . The method of  claim 1  wherein an effective amount of VEGF is administered to increase keratinocyte migration to the treated skin. 
     
     
         6 . The method of  claim 1  further comprising removing or scrubbing off some or all of the epidermal layer of the skin to be treated prior to or at the time of administration of the VEGF. 
     
     
         7 . The method of  claim 1  wherein an effective amount of VEGF is administered to promote increase keratinocyte migration, fibroblast proliferation and infiltration of macrophages. 
     
     
         8 . The method of  claim 7  wherein an effective amount of VEGF is administered to promote fibroblast proliferation to the skin to be treated. 
     
     
         9 . The method of  claim 7  wherein the VEGF is administered in an amount effective to promote collagen deposition. 
     
     
         10 . The method of  claim 7  wherein the amount of collagen decreases wrinkling or sagging of the skin. 
     
     
         11 . The method of  claim 7  wherein the collagen is oriented to increase stability of the dermis and decrease susceptibility to degradation. 
     
     
         12 . The method of  claim 1  wherein the VEGF is administered in an amount effective to stimulate infiltration of macrophages into the skin to be treated. 
     
     
         13 . The method of  claim 1  wherein the VEGF is administered in an amount effective to increase sub-dermal fat. 
     
     
         14 . The method of  claim 1  wherein the VEGF is administered to the skin in combination with an exfolliant or laser treatment. 
     
     
         15 . The method of  claim 1  wherein the VEGF is administered to the skin following or at the time of surgical removal or reshaping of the skin. 
     
     
         16 . The method of  claim 1  wherein the composition is administered to aged skin. 
     
     
         17 . The method of  claim 1  wherein the composition is administered to injured skin. 
     
     
         18 . The method of  claim 1  wherein the composition is administered to skin damaged by disease or sun. 
     
     
         19 . The method of  claim 1 , wherein at least about 1×10 7  recombinant viral particles are administered to the skin. 
     
     
         20 . A formulation for use in the method of  claims 1 .