The mucoadhesive and gastroretentive properties of hydrophobin-coated porous silicon nanoparticle oral drug delivery systems

Biomaterials. 2012 Apr;33(11):3353-62. doi: 10.1016/j.biomaterials.2012.01.029. Epub 2012 Jan 29.

Abstract

Impediments to intestinal absorption, such as poor solubility and instability in the variable conditions of the gastrointestinal (GI) tract plague many of the current drugs restricting their oral bioavailability. Particulate drug delivery systems hold great promise in solving these problems, but their effectiveness might be limited by their often rapid transit through the GI tract. Here we describe a bioadhesive oral drug delivery system based on thermally-hydrocarbonized porous silicon (THCPSi) functionalized with a self-assembled amphiphilic protein coating consisting of a class II hydrophobin (HFBII) from Trichoderma reesei. The HFBII-THCPSi nanoparticles were found to be non-cytotoxic and mucoadhesive in AGS cells, prompting their use in a biodistribution study in rats after oral administration. The passage of HFBII-THCPSi nanoparticles in the rat GI tract was significantly slower than that of uncoated THCPSi, and the nanoparticles were retained in stomach by gastric mucoadhesion up to 3 h after administration. Upon entry to the small intestine, the mucoadhesive properties were lost, resulting in the rapid transit of the nanoparticles through the remainder of the GI tract. The gastroretentive drug delivery system with a dual function presented here is a viable alternative for improving drug bioavailability in the oral route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesiveness
  • Administration, Oral
  • Animals
  • Coated Materials, Biocompatible
  • Fungal Proteins / chemistry*
  • Fungal Proteins / pharmacokinetics*
  • Gastric Mucosa / metabolism*
  • Gastrointestinal Tract / metabolism*
  • Intestinal Absorption / physiology*
  • Male
  • Metabolic Clearance Rate
  • Nanocapsules / administration & dosage
  • Nanocapsules / chemistry*
  • Organ Specificity
  • Porosity
  • Rats, Wistar
  • Silicon
  • Tissue Distribution

Substances

  • Coated Materials, Biocompatible
  • Fungal Proteins
  • Nanocapsules
  • Silicon