Ultra-flexible nanocarriers for enhanced topical delivery of a highly lipophilic antioxidative molecule for skin cancer chemoprevention

Cedar H.A. Boakye, Ketan Patel, Ravi Doddapaneni, Arvind Bagde, Nusrat Chowdhury, Stephen Safe, Mandip Singh

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Purpose: In this study, we developed cationic ultra-flexible nanocarriers (UltraFLEX-Nano) to surmount the skin barrier structure and to potentiate the topical delivery of a highly lipophilic antioxidative diindolylmethane derivative (DIM-D) for the inhibition of UV-induced DNA damage and skin carcinogenesis. Methods: UltraFLEX-Nano was prepared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol and tween-80 by ethanolic injection method; was characterized by Differential Scanning Calorimetric (DSC), Fourier Transform Infrared (FT-IR) and Atomic Force Microscopic (phase-imaging) analyses and permeation studies were performed in dermatomed human skin. The efficacy of DIM-D-UltraFLEX-Nano for skin cancer chemoprevention was evaluated in UVB-induced skin cancer model in vivo. Results: DIM-D-UltraFLEX-Nano formed a stable mono-dispersion (110.50 ± 0.71 nm) with >90% encapsulation of DIM-D that was supported by HPLC, DSC, FT-IR and AFM phase imaging. The blank formulation was non-toxic to human embryonic kidney cells. UltraFLEX-Nano was vastly deformable and highly permeable across the stratum corneum; there was significant (p < 0.01) skin deposition of DIM-D for UltraFLEX-Nano that was superior to PEG solution (13.83-fold). DIM-D-UltraFLEX-Nano pretreatment delayed the onset of UVB-induced tumorigenesis (2 weeks) and reduced (p < 0.05) the number of tumors observed in SKH-1 mice (3.33-fold), which was comparable to pretreatment with sunscreen (SPF30). Also, DIM-D-UltraFLEX-Nano caused decrease (p < 0.05) in UV-induced DNA damage (8-hydroxydeoxyguanosine), skin inflammation (PCNA), epidermal hyperplasia (c-myc, CyclinD1), immunosuppression (IL10), cell survival (AKT), metastasis (Vimentin, MMP-9, TIMP1) but increase in apoptosis (p53 and p21). Conclusion: UltraFLEX-Nano was efficient in enhancing the topical delivery of DIM-D. DIM-D-UltraFLEX-Nano was efficacious in delaying skin tumor incidence and multiplicity in SKH mice comparable to sunscreen (SPF30).

Original languageEnglish (US)
Pages (from-to)156-167
Number of pages12
JournalColloids and Surfaces B: Biointerfaces
Volume143
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Keywords

  • Chemoprevention
  • Diindolymethane (DIM)
  • Phytochemicals
  • Skin cancer
  • Skin delivery
  • Topical delivery
  • Ultra deformable nanocarriers

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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