Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery

Drug Dev Ind Pharm. 2019 Apr;45(4):629-641. doi: 10.1080/03639045.2019.1569031. Epub 2019 Jan 28.

Abstract

Objective: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.

Methods: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.

Results: Particles with an average size of 25-40 nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.

Conclusion: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.

Keywords: Carbopol 934; Eudragit S100; Piroxicam; hydrogel; nanoprecipitation; pH responsive; transdermal drug delivery.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Drug Carriers / chemistry*
  • Drug Liberation*
  • Hydrogels / chemistry
  • Hydrogen-Ion Concentration
  • Mice
  • Nanoparticles / chemistry
  • Particle Size
  • Piroxicam / administration & dosage
  • Piroxicam / chemistry
  • Piroxicam / pharmacokinetics
  • Polymethacrylic Acids / chemistry
  • Skin / drug effects
  • Skin / metabolism
  • Skin Absorption / drug effects
  • Solubility

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Hydrogels
  • Polymethacrylic Acids
  • Piroxicam
  • methylmethacrylate-methacrylic acid copolymer