The structure and composition of liposomes can affect skin regeneration, morphology and growth factor expression in acute wounds.
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.
Jeschke
M G
MG
Galveston Burns Unit and Department of Surgery, Shriners Hospital for Children, University Texas Medical Branch, TX 77550, USA.
Sandmann
G
G
Finnerty
C C
CC
Herndon
D N
DN
Pereira
C T
CT
Schubert
T
T
Klein
D
D
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002784:Cholesterol / Q000008:administration & dosage*; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage / Q000737:chemistry; D051523:Fibroblast Growth Factor 7 / Q000032:analysis; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D008970:Molecular Weight; D018919:Neovascularization, Physiologic; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D011487:Protein Conformation; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism / Q000628:therapy*
D005229:Fatty Acids, Monounsaturated; D006133:Growth Substances; D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D008081:Liposomes; D010982:Platelet-Derived Growth Factor; D000644:Quaternary Ammonium Compounds; D042461:Vascular Endothelial Growth Factor A; D051523:Fibroblast Growth Factor 7; C087276:(3-dimyristyloxypropyl)(dimethyl)(hydroxyethyl)ammonium; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane