Diffusion studies of nanometer polymersomes across tissue engineered human oral mucosa

Pharm Res. 2009 Jul;26(7):1718-28. doi: 10.1007/s11095-009-9882-6. Epub 2009 Apr 22.

Abstract

Purpose: To measure the diffusion of nanometer polymersomes through tissue engineered human oral mucosa.

Methods: In vitro models of full thickness tissue engineered oral mucosa (TEOM) were used to assess the penetration properties of two chemically different polymersomes comprising two of block copolymers, PMPC-PDPA and PEO-PDPA. These copolymers self-assemble into membrane-enclosed vesicular structures. Polymersomes were conjugated with fluorescent rhodamine in order to track polymersome diffusion. Imaging and quantification of the diffusion properties were assessed by confocal laser scanning microscopy (CLSM).

Results: TEOM is morphologically similar to natural oral mucosa. Using CLSM, both formulations were detectable in the TEOM within 6 h and after 48 h both penetrated up to 80 microm into the TEOM. Diffusion of PMPC-PDPA polymersomes was widespread across the epithelium with intra-epithelial uptake, while PEO-PDPA polymersomes also diffused into the epithelium.

Conclusions: CLSM was found to be an effective and versatile method for analysing the level of diffusion of polymersomes into TEOM. The penetration and retention of PMPC-PDPA and PEO-PDPA polymersomes means they may have potential for intra-epithelial drug delivery and/or trans-epithelial delivery of therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Cells, Cultured
  • Diffusion
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics*
  • Fibroblasts / metabolism
  • Humans
  • Keratinocytes / metabolism
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry
  • Microscopy, Confocal
  • Mouth Mucosa / metabolism*
  • Mouth Mucosa / ultrastructure
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / chemical synthesis
  • Phosphorylcholine / chemistry
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polymethacrylic Acids / chemical synthesis
  • Polymethacrylic Acids / chemistry*
  • Tissue Engineering / methods*

Substances

  • Drug Carriers
  • Methacrylates
  • Polymethacrylic Acids
  • poly(2-(diisopropylamino)ethyl methacrylate)
  • poly(2-methacryloyloxyethyl-phosphorylcholine)
  • Phosphorylcholine
  • Polyethylene Glycols