Pharmaceutical Research

, Volume 26, Issue 7, pp 1718–1728 | Cite as

Diffusion Studies of Nanometer Polymersomes Across Tissue Engineered Human Oral Mucosa

  • Vanessa Hearnden
  • Hannah Lomas
  • Sheila MacNeil
  • Martin Thornhill
  • Craig Murdoch
  • Andrew Lewis
  • Jeppe Madsen
  • Adam Blanazs
  • Steve Armes
  • Giuseppe Battaglia
Research Paper

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 μm 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.

KEY WORDS

confocal laser scanning microscopy diffusion epithelium oral mucosa polymersome 

Abbreviations

ALI

Air liquid interface

ATRP

Atomic transfer radical polymerisation

CLSM

Confocal laser scanning microscopy

DED

De-epithelialized dermis

PEO23-PDPA15

Poly(ethylene oxide)-poly(2-(diisopropylamino)ethyl methacrylate)

PMPC25-PDPA70

2-(Methacryloyloxy)ethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate

THF

Tetrahydrofuran

TEM

Transmission electron microscopy

TEOM

Tissue engineered oral mucosa

Notes

Acknowledgments

We would like to thank Dr. Anthony Bullock, Dr. Helen Colley, Mr. Tom Smart and Ms. Marzia Massignani for their help and guidance. This work was supported by funding from EPSRC (DTA PhD studentship to Vanessa Hearnden) and Biocompatibles UK Ltd.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Vanessa Hearnden
    • 1
    • 2
  • Hannah Lomas
    • 1
  • Sheila MacNeil
    • 1
  • Martin Thornhill
    • 2
  • Craig Murdoch
    • 2
  • Andrew Lewis
    • 3
  • Jeppe Madsen
    • 4
  • Adam Blanazs
    • 4
  • Steve Armes
    • 4
  • Giuseppe Battaglia
    • 1
  1. 1.Biomaterials and Tissue Engineering Group, Department of Engineering Materials, Kroto Research Institute, North CampusUniversity of SheffieldSheffieldUK
  2. 2.Department of Oral & Maxillofacial Medicine & Surgery, School of Clinical DentistryUniversity of SheffieldSheffieldUK
  3. 3.Biocompatibles UK Ltd.FarnhamUK
  4. 4.Department of ChemistryUniversity of SheffieldSheffieldUK

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