Impact of C-Phycocyanin-Loaded Transfersomes on Early Epidermal Proliferation in a Murine Skin Carcinogenesis Model

Abstract

Background: Early tumor-promoting events in skin carcinogenesis are characterized by increased keratinocyte proliferation, epidermal hyperplasia, and architectural alterations of the skin. Natural bioactive compounds with antiproliferative properties may represent promising chemopreventive strategies. C-phycocyanin (C-PC), a cyanobacteria - derived biliprotein, has demonstrated cytostatic and anti-inflammatory effects in experimental models (1-2). However, its topical delivery and influence on early tumor promotion require further investigation. Aim(s): To evaluate whether C-PC-loaded transfersomes modulate early proliferation- and dysplasiaassociated alterations in a mouse DMBA/TPA model of skin tumor promotion. Methods: Experimental skin carcinogenesis was induced using a classical DMBA/TPA initiation– promotion protocol. Animals were treated with C-PC-loaded transfersomes, empty transfersomes, or cancerogenic formulations. Histological assessment included epidermal thickness, rete ridge depth, and dysplasia grading. Immunohistochemical analysis of Ki-67 expression was performed separately in basal and suprabasal epidermal layers. Correlation analysis between suprabasal Ki-67 index and histopathological parameters was conducted. Statistical analysis included Welch’s ANOVA with Games–Howell post hoc test, Kruskal–Wallis analysis, and Spearman correlation (p < 0.05). Results: Tumor promotion induced marked epidermal hyperplasia, increased rete ridge formation, and elevated Ki-67 expression extending into suprabasal layers. Treatment with C-PC-loaded transfersomes significantly reduced epidermal thickness and suprabasal proliferative activity compared to untreated promoted skin. Suprabasal Ki-67 index positively correlated with epidermal thickness, rete ridge depth, and dysplasia grade, indicating its sensitivity as a marker of early pathological proliferation. Conclusion: Topical delivery of C-PC via transfersomes was associated with attenuation of early proliferative and structural alterations during skin tumor promotion in this experimental model. Further studies are required to clarify the underlying mechanisms and to determine their potential relevance in long-term chemopreventive strategies.