Development and In Vitro Evaluation of Vitamin E-Enriched Nanoemulsion Vehicles Loaded with Genistein for Chemoprevention Against UVB-Induced Skin Damage

J Pharm Sci. 2015 Oct;104(10):3510-23. doi: 10.1002/jps.24547. Epub 2015 Jun 24.

Abstract

There is a great need for effective protection against cutaneous pathologies arising from chronic exposure to harmful solar UVB radiations. A promising pharmaceutical strategy to improve the efficacy of chemotherapeutic/preventative natural compounds (e.g., soy isoflavone Genistein, Gen) is to enhance their dermal delivery using nanoemulsion (NE) formulations. This report investigates the development of nanoemulsified tocotrienol(T3)-rich fraction of red palm oil (Tocomin®), to yield an optimal NE delivery system for dermal photoprotection (z-average size <150 nm, ζ-potential ≈ -30 mV, polydispersity index < 0.25). Physicochemical characterization and photostability studies indicate NE formulations utilizing surfactant mixture (Smix) of Solutol® HS-15 (SHS15) blended with vitamin E TPGS (TPGS) as cosurfactant was significantly superior to formulations that utilized Lutrol® F68 (LF68) as the cosurfactant. A ratio of 60:40 of SHS15-TPGS-NE was further identified as lead Tocomin® NE topical platform using in vitro pharmaceutical skin reactivity studies that assess cutaneous irritancy and cytotoxicity. Prototype Tocomin® NE loaded with the antiphotocarcinogenic molecule Gen (Gen-Tocomin® NE) showed slow-release profile in both liquid and cream forms. Gen-Tocomin® NE also showed excellent biocompatibility, and provided substantial UVB protection to cultured subcutaneous L929 fibroblasts, indicating the great potential of our Tocomin® NE warranting further prototype development as topical pharmaceutical platform for skin photoprotection applications.

Keywords: biocompatibility; cancer chemoprevention; controlled release; in vitro models; nanoemulsion; photoprotection; physicochemical properties; self-emulsifying; skin reactivity; tocotrienol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Dogs
  • Drug Delivery Systems
  • Drug Stability
  • Emulsions
  • Genistein / administration & dosage*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Nanostructures
  • Palm Oil
  • Pharmaceutical Vehicles
  • Plant Oils
  • Skin Aging / drug effects*
  • Skin Aging / radiation effects*
  • Skin Neoplasms / prevention & control
  • Surface-Active Agents
  • Ultraviolet Rays
  • Vitamin E / administration & dosage*
  • Vitamin E / chemistry

Substances

  • Anticarcinogenic Agents
  • Emulsions
  • Pharmaceutical Vehicles
  • Plant Oils
  • Surface-Active Agents
  • Vitamin E
  • Palm Oil
  • Genistein