Percutaneous delivery of
growth factors is often used to treat
wounds, and for cosmetic purposes, as a way of accelerating healing and skin regeneration, respectively. However, the
therapeutic effects of
growth factors are diminished by their poor absorption when delivered percutaneously, in addition to their rapid degradation by
proteinases. To overcome these obstacles, we constructed two skin-permeable compounds.
Basic fibroblast growth factor (bFGF) and
vascular endothelial growth factor-A (
VEGF-A) were both genetically paired with low-molecular-weight
protamine (LMWP), to yield the compounds LMWP-bFGF and LMWP-
VEGF-A, respectively. The molecular weights and N-terminal amino acid sequences of LMWP-bFGF and LMWP-
VEGF-A confirmed that the N-terminus-specific conjugation of LMWP with bFGF and
VEGF-A had been successful. The biological abilities of the native factors to stimulate human fibroblast (CCD-986sk) and endothelial cell proliferation were preserved. Both compounds significantly promoted
wound (scratch) recovery and enhanced
procollagen type I C-peptide synthesis in CCD-986sk cells (to levels 184 and 133% those of the native compounds, respectively). The LMWP-conjugated
growth factors were significantly more permeable than the native forms (by 7.29- and 29.22-fold, respectively). Finally, encapsulation of the compounds in positively charged elastic nanoliposomes (115 ± 1.54 nm in diameter with a zeta potential of 57.2 ± 3.05 mV) further improved both permeation and stability. Thus, nanoliposomes loaded with LMWP-conjugated
growth factors are expected to enhance skin regeneration; the materials will find applications in wound-healing
therapies and anti-wrinkle
cosmetics.