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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery

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Souza, Joel G. [1] ; Dias, Karina [1] ; Silva, Silas A. M. [2] ; de Rezende, Lucas C. D. [1] ; Rocha, Eduardo M. [3] ; Emery, Flavio S. [1] ; Lopez, Renata F. V. [1]
Total Authors: 7
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, BR-14040903 Ribeirao Preto, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Med, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Ophthalmol, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF CONTROLLED RELEASE; v. 200, p. 115-124, FEB 28 2015.
Web of Science Citations: 24

Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by C-13-NMR, H-1-NMR and DOSY. PAMAMG3.5 and PAMAMG4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3.5, respectively. In vivo experiments, however, revealed that iontophoresis of Dex-PAMAM-G3.5 increased Dex concentration in the aqueous humor by 6.6-fold, while iontophoresis of Dex-PAMAM G4 and Dex increased it 2.5 and 2-fold, respectively. Therefore, iontophoresis targeted PAMAM to the cornea but it is the sustained delivery of the Dex from PAMAM that prevents its rapid elimination from the aqueous humor. In conclusion, iontophoresis of PAMAM complexes represents a promising strategy for targeted and sustained topical drug delivery to the eye. (C) 2015 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 11/11305-1 - Dendrimers as nanocarriers in the ocular administration of drugs using iontophoresis
Grantee:Renata Fonseca Vianna Lopez
Support Opportunities: Regular Research Grants
FAPESP's process: 10/19210-7 - Potential evaluation of dendrimer and iontophoresis association for ocular drugs administration
Grantee:Joel Gonçalves de Souza
Support Opportunities: Scholarships in Brazil - Doctorate