Multifunctional Nanotube-Mucoadhesive Poly(methyl vinyl ether-co-maleic acid)@Hydroxypropyl Methylcellulose Acetate Succinate Composite for Site-Specific Oral Drug Delivery

Adv Healthc Mater. 2017 Oct;6(20). doi: 10.1002/adhm.201700629. Epub 2017 Jul 17.

Abstract

An advanced oral drug delivery system that can effectively deliver drugs with poor oral bioavailability is strongly desirable. Herein, a multifunctional nano-in-micro structured composite is developed by encapsulation of the mucoadhesive poly(methyl vinyl ether-co-maleic acid) modified halloysite nanotubes (HNTs) with the pH-responsive hydroxypropyl methylcellulose acetate succinate by the microfluidics to control the drug release, increase cell-particle interaction, and improve drug absorption. The microparticles show spherical shape, homogeneous particle size distribution (58 ± 1 µm), and pH-responsive dissolution behavior at pH > 6, and they prevent the premature release of curcumin in simulated pH conditions of the stomach and immediately release the curcumin in simulated pH conditions of the small intestine. The surface modification of HNT with mucoadhesive poly(methyl vinyl ether-co-maleic acid) significantly enhances its interactions with the intestinal Caco-2/HT29-MTX cells and the mouse small intestines, and increases the permeability of curcumin across the co-cultured Caco-2/HT29-MTX cell monolayers by about 13 times compared to the free curcumin. Therefore, the developed multifunctional nanotube-mucoadhesive poly(methyl vinyl ether-co-maleic acid)@hydroxypropyl methylcellulose acetate succinate composite is a promising oral drug delivery system for drugs with poor oral bioavailability.

Keywords: curcumin; halloysite nanotubes; microfluidics; oral drug delivery; pH-responsive.

MeSH terms

  • Administration, Oral
  • Animals
  • Caco-2 Cells
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Curcumin / chemistry
  • Curcumin / metabolism
  • Curcumin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacology
  • Drug Liberation
  • HT29 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Intestine, Small / metabolism
  • Maleates / chemistry*
  • Methyl Ethers / chemistry*
  • Methylcellulose / analogs & derivatives*
  • Methylcellulose / chemistry
  • Mice
  • Nanotubes / chemistry*
  • Particle Size
  • Permeability / drug effects
  • Polyvinyls / chemistry*

Substances

  • Drug Carriers
  • Maleates
  • Methyl Ethers
  • Polyvinyls
  • poly(vinyl methyl ether)
  • hydroxypropylmethylcellulose acetate succinate
  • Methylcellulose
  • maleic acid
  • Curcumin