043The Structure and Composition of Liposomes can Affect Skin Regeneration, Morphology, and Growth Factor Expression in Acute Wounds

Introduction: Liposomal gene transfer is an effective therapeutic approach for the treatment of several pathophysiologic states. 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. Methods: 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 molecular mechanisms after gene transfer, protein expression, dermal, and epidermal regeneration. Results: DOTAP/Chol increased IGF‐I and KGF protein concentration and caused concomitant cellular responses, e.g., by increasing IGFBP‐3, p < 0.05. DOTAP/Chol liposomes improved epidermal regeneration by exhibiting the most rapid area and linear wound reepithelization compared to DMRIE or control, p < 0.001. DOTAP/Chol and DMRIE exerted promitogenic and anti‐apoptotic 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 VEGF concentrations and thus neovascularization when compared with DMRIE and saline, p < 0.001. Summary: 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. Acknowledgments: Clayton Foundation for Research