Nanoparticles for local drug delivery to the oral mucosa: proof of principle studies.

Abstract

PURPOSE:

To determine if solid lipid nanoparticles represent a viable strategy for local delivery of poorly water soluble and unstable chemopreventive compounds to human oral tissues.

METHODS:

Nanoparticle uptake and compound retention evaluations employed monolayer-cultured human oral squamous cell carcinoma (OSCC) cell lines and normal human oral mucosal explants. Feasibility of nanoparticle delivery was also evaluated with respect to the presence of phase-III efflux transporters in normal oral mucosal tissue and OSCC tissues.

RESULTS:

Functional uptake assays confirmed significantly greater internalization of nanoparticle-delivered fluorescent probe relative to free-fluorescent probe delivery, while concurrently demonstrating nanoparticle uptake rate differences among the OSCC cell lines and the phagocytic control human monocyte cell line. Mucosal explants exhibited nanoparticle penetration and internalization in the spinous and basal epithelial layers (7/10 specimens), and also exhibited the presence of the phase-III efflux transporters multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP).

CONCLUSIONS:

These data confirm nanoparticle internalization by OSCC cells and support the premise that nanoparticle-based delivery provides higher final intracellular levels relative to bolus administration. Furthermore, the penetration and subsequent internalization of nanoparticles within the proliferating basal layer cells demonstrates the feasibility of nanoparticle formulations for local delivery and stabilization of oral chemopreventive compounds.

• Authors: Andrew S Holpuch, Garrett J Hummel, Meng Tong, Garrett A Seghi, Ping Pei, Ping Ma, Russell J Mumper, Susan R Mallery
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 7 Pg. 1224-36 (Jul 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 20354767 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoic acid
• Antibiotics, Antineoplastic
• Boron Compounds
• Fluorescent Dyes
• Idarubicin

Topics

• Antibiotics, Antineoplastic (administration & dosage, pharmacokinetics)
• Blotting, Western
• Boron Compounds (administration & dosage, pharmacokinetics)
• Carcinoma, Squamous Cell (prevention & control)
• Cells, Cultured
• Drug Delivery Systems
• Fluorescent Dyes (administration & dosage, pharmacokinetics)
• Humans
• Idarubicin (administration & dosage, pharmacokinetics)
• Immunohistochemistry
• Mouth Mucosa (metabolism, pathology)
• Nanoparticles (administration & dosage)