pH triggered and charge attracted nanogel for simultaneous evaluation of penetration and toxicity against skin cancer: In-vitro and ex-vivo study

Int J Biol Macromol. 2019 May 1:128:740-751. doi: 10.1016/j.ijbiomac.2019.01.147. Epub 2019 Jan 27.

Abstract

The current research is focused to develop and investigate the toxicity and penetration potential of biocompatible chitosan nanogel encapsulating capecitabine by ionic interaction mechanism exhibiting pH triggered transdermal targeting. The nanogel (CPNL) was synthesized by ion gelation mechanism using Pluronic F 127 and surface decoration by Transcutol as non-ionic penetration enhancer. The CPNL possesses fine morphology and nano size range when evaluated by TEM, SEM and DLS analysis with cationic charge and slightly acidic pH assayed by zeta potential and pH analysis. It showed pH responsive drug release characteristics mimicking the skin cancer micro-environment. The MTT assay and apoptotic index of CPNL on HaCaT cell line elaborated optimal cell toxicity and retention on 24h of exposure. The ex-vivo skin penetration analysis exhibited noteworthy diffusion and penetration caliber through concentration depth profile, steady state flux and fluorescent skin imaging on porcine tissue. Overall outcomes suggested CPNL as a potent alternative biocompatible, transdermal nanotherapy against skin cancer displaying significant penetration caliber with enhance toxicity on cancerous cell.

Keywords: Capecitabine; Nanogel; Skin cancer.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Capecitabine / chemistry
  • Capecitabine / pharmacology
  • Capecitabine / therapeutic use
  • Cell Line
  • Chitosan / chemistry
  • Diffusion
  • Drug Carriers / chemistry*
  • Drug Carriers / toxicity*
  • Drug Liberation
  • Ethylene Glycols / chemistry
  • Gels
  • Humans
  • Hydrogen-Ion Concentration
  • Nanostructures / chemistry*
  • Particle Size
  • Permeability
  • Poloxamer / chemistry
  • Skin / metabolism
  • Skin Neoplasms / drug therapy*
  • Surface Properties

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Ethylene Glycols
  • Gels
  • Poloxamer
  • Capecitabine
  • Chitosan
  • carbitol