Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrating polymer network hydrogels based on hyaluronic acid/poly (N-isopropylacrylamide) for transdermal delivery of luteolin

Int J Biol Macromol. 2018 Oct 15;118(Pt A):731-740. doi: 10.1016/j.ijbiomac.2018.06.061. Epub 2018 Jun 27.

Abstract

In this study, we prepared double cross-linked interpenetrating polymer network (IPN) hydrogels composed of temperature sensitive poly (N-isopropylacrylamide) (PNIPAM) and pH sensitive hyaluronic acid (HA) by radical polymerization and Michael addition. Their physicochemical properties for transdermal delivery of luteolin inhibiting the hyperproliferation of keratinocytes in psoriasis were investigated and drug release studies were performed. Double networks of HA/PNIPAM IPN hydrogel were identified through FT-IR and 13CNMR. By measuring the swelling ratios pH and temperature sensitivity were confirmed, and it was influenced by the content of a cross-linking agent. As a result of texture analysis and rheometry, a IPN hydrogel with 3% crosslinker content had the most adhesive and stable cross-linked network. Therefore, luteolin was loaded on this hydrogel. Its drug release behavior was determined at various temperatures and pH using several drug release kinetic models. As a result of skin permeation study, HA/PNIPAM IPN hydrogel effectively delivers luteolin to the epidermis and dermis. No toxicity was observed as a result of observing cytotoxicity of the hydrogel for application to the skin. In conclusion, IPN hydrogels can be developed as carriers of transdermal delivery system of luteolin for psoriasis skin relief.

Keywords: Interpenetrating polymer network hydrogel; Luteolin; Temperature-sensitive; pH-sensitive.

MeSH terms

  • Acrylic Resins* / chemistry
  • Acrylic Resins* / pharmacokinetics
  • Acrylic Resins* / pharmacology
  • Administration, Cutaneous
  • Animals
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / pharmacology
  • Hot Temperature*
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacokinetics
  • Hyaluronic Acid* / pharmacology
  • Hydrogels* / chemistry
  • Hydrogels* / pharmacokinetics
  • Hydrogels* / pharmacology
  • Keratinocytes / metabolism
  • Luteolin* / chemistry
  • Luteolin* / pharmacokinetics
  • Luteolin* / pharmacology
  • Skin Absorption / drug effects*
  • Swine
  • Swine, Miniature

Substances

  • Acrylic Resins
  • Delayed-Action Preparations
  • Hydrogels
  • Hyaluronic Acid
  • Luteolin