Diffusion studies of nanometer polymersomes across tissue engineered human oral mucosa.
OBJECTIVE
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.
Hearnden
Vanessa
V
Biomaterials and Tissue Engineering Group, Department of Engineering Materials, Kroto Research Institute, North Campus, University of Sheffield, Broad Lane, Sheffield S37HQ, UK.
Lomas
Hannah
H
Macneil
Sheila
S
Thornhill
Martin
M
Murdoch
Craig
C
Lewis
Andrew
A
Madsen
Jeppe
J
Blanazs
Adam
A
Armes
Steve
S
Battaglia
Giuseppe
G
D001692:Biological Transport; D002478:Cells, Cultured; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry; D018613:Microscopy, Confocal; D009061:Mouth Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
D004337:Drug Carriers; D008689:Methacrylates; D011109:Polymethacrylic Acids; C511861:poly(2-(diisopropylamino)ethyl methacrylate); C115766:poly(2-methacryloyloxyethyl-phosphorylcholine); D010767:Phosphorylcholine; D011092:Polyethylene Glycols