Transbuccal Delivery of CNS Therapeutic Nanoparticles: Synthesis, Characterization, and in Vitro Permeation Studies

Abstract

This work utilized polyamidoamine (PAMAM) dendrimer G4.5 as the underlying carrier to construct central nervous system (CNS) therapeutic nanoparticles and explored the buccal mucosa as an alternative absorption site for administration of the dendritic nanoparticles. Opioid peptide DPDPE was chosen as a model CNS drug. It was coupled to PAMAM dendrimer G4.5 with polyethylene glycol (PEG) (i.e., PEG-G4.5-DPDPE) or with PEG and transferrin receptor monoclonal antibody OX26 (i.e., OX26-PEG-G4.5-DPDPE). The therapeutic dendritic nanoparticles labeled with 5-(aminoacetamido) fluorescein (AAF) were studied for transbuccal transport using a vertical Franz diffusion cell system mounted with porcine buccal mucosa. For comparison, AAF-labeled PAMAM dendrimers G3.5 and G4.5 and fluorescein isothiocynate (FITC)-labeled G3.0 and G4.0 were also tested for transbuccal delivery. The permeability of PEG-G4.5 (AAF)-DPDPE and OX26-PEG-G4.5(AAF)-DPDPE were on the order of 10 -7-10 -6 cm/s. Coadministration of bile salt sodium glycodeoxycholate (NaGDC) enhanced the permeability of dendritic nanoparticles by multiple folds. Similarly, a multifold increase of permeability of dendritic nanoparticles across the porcine buccal mucosal resulted from the application of mucoadhesive gelatin/PEG semi-interpenetrating network (sIPN). These results indicate that transbuccal delivery is a possible route for administration of CNS therapeutic nanoparticles.

Department(s)

Chemical and Biochemical Engineering

Keywords and Phrases

Buccal mucosa; central nervous system (CNS); dendrimer; encephalin; nanomedicine; transbuccal delivery

International Standard Serial Number (ISSN)

1948-7193

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2011 American Chemical Society (ACS), All rights reserved.

Publication Date

16 Nov 2011

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