Liposomal gene transfer is an effective therapeutic approach to improve dermal and epidermal regeneration. The purpose of the present study was to define whether the
biological or chemical structure of a
liposome influences cellular and
biological regeneration in the skin, and to determine by which mechanisms possible changes occur. Rats were inflicted a full-excision acute
wound and divided into three groups to receive weekly
subcutaneous injections of
DMRIE liposomes plus the Lac Z gene, or
DOTAP/Chol
liposomes plus the Lac Z gene, or saline. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine cellular responses after gene transfer,
protein expression, dermal and epidermal regeneration.
DOTAP/Chol increased
IGF-I and KGF
protein concentration and caused concomitant cellular responses, for example, by increasing
IGFBP-3, P<0.05.
DOTAP/Chol
liposomes improved epidermal regeneration by exhibiting the most rapid area and linear
wound re-epithelization compared to
DMRIE or control, P<0.001.
DOTAP/Chol and
DMRIE exerted promitogenic and antiapoptotic effects on basal keratinocytes, P<0.05. Dermal regeneration was improved in
DOTAP/Chol-treated animals by an increased
collagen deposition and morphology, P<0.001.
DOTAP/Chol
liposomes increased
vascular endothelial growth factor concentrations and thus neovascularization when compared with
DMRIE and saline, P<0.001. In the present study, we showed that different
liposomes have different effects on intracellular and
biological responses based on its chemical and molecular structure. For gene transfer in acute
wounds, the administration of
DOTAP/Chol
liposomes appears to be beneficial.