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Gels 2017, 3(2), 22; doi:10.3390/gels3020022

Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases

1
Department of Drug Science and Technology, University of Torino, via P. Giuria 9, 10125 Torino, Italy
2
Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, USA
3
Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Gaio Paradossi
Received: 10 March 2017 / Revised: 29 May 2017 / Accepted: 1 June 2017 / Published: 8 June 2017
(This article belongs to the Special Issue Micro- and Nanogels)
View Full-Text   |   Download PDF [5707 KB, uploaded 8 June 2017]   |  

Abstract

Glucocorticoids are widely prescribed in treatment of rheumatoid arthritis, asthma, systemic lupus erythematosus, lymphoid neoplasia, skin and eye inflammations. However, well-documented adverse effects offset their therapeutic advantages. In this work, novel nano-hydrogels for the sustained delivery of dexamethasone were designed to increase both bioavailability and duration of the administered drug and reducing the therapeutic dose. Hydrogels are soft materials consisting of water-swollen cross-linked polymers to which the insertion of cyclodextrin (CD) moieties adds hydrophobic drug-complexing sites. Polyamidoamines (PAAs) are biocompatible and biodegradable polymers apt to create CD moieties in hydrogels. In this work, β or γ-CD/PAA nanogels have been developed. In vitro studies showed that a pretreatment for 24–48 h with dexamethasone-loaded, β-CD/PAA nanogel (nanodexa) inhibits adhesion of Jurkat cells to human umbilical vein endothelial cells (HUVEC) in conditions mimicking inflammation. This inhibitory effect was faster and higher than that displayed by free dexamethasone. Moreover, nanodexa inhibited COX-2 expression induced by PMA+A23187 in Jurkat cells after 24–48 h incubation in the 10−8–10−5 M concentration range, while dexamethasone was effective only at 10−5 M after 48 h treatment. Hence, the novel nanogel-dexamethasone formulation combines faster action with lower doses, suggesting the potential for being more manageable than the free drug, reducing its adverse side effects. View Full-Text
Keywords: dexamethasone; cyclodextrin/polyamidoamine nanohydrogels; topical delivery; β- and γ-Cyclodextrins; COX-2 expression dexamethasone; cyclodextrin/polyamidoamine nanohydrogels; topical delivery; β- and γ-Cyclodextrins; COX-2 expression
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Argenziano, M.; Dianzani, C.; Ferrara, B.; Swaminathan, S.; Manfredi, A.; Ranucci, E.; Cavalli, R.; Ferruti, P. Cyclodextrin-Based Nanohydrogels Containing Polyamidoamine Units: A New Dexamethasone Delivery System for Inflammatory Diseases. Gels 2017, 3, 22.

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