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Development of solid nanoparticles based on hydroxypropyl-β-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium

Gavini, Elisabetta and Spada, Gianpiera and Rassu, Giovanna and Cerri, Guido and Brundu, Antonio and Cossu, Massimo and Sorrenti, Milena and Giunchedi, Paolo (2011) Development of solid nanoparticles based on hydroxypropyl-β-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium. Journal of Pharmacy and Pharmacology, Vol. 63 (4), p. 472-482. eISSN 2042-7158. Article.

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DOI: 10.1111/j.2042-7158.2010.01220.x

Abstract

Objectives  Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs.
Methods  Preparation parameters were studied in order to develop solid pH-dependent drug-release nanoparticles, constituted by hydroxypropyl-β-cyclodextrin and/or Eudragit® L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion-evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced.

Key findings  Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH-dependent drug-release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa.

Conclusions  Formulations containing hydroxypropyl-β-cyclodextrin represent new colon-targeted nanoparticles for transmucosal delivery of drugs.

Item Type:Article
ID Code:6589
Status:Published
Refereed:Yes
Uncontrolled Keywords:Colon delivery, Eudragit L 100, hydroxypropyl-β-cyclodextrin, solid nanoparticles, transmucosal administration
Subjects:Area 03 - Scienze chimiche > CHIM/09 Farmaceutico tecnologico applicativo
Area 04 - Scienze della terra > GEO/09 Georisorse minerarie e applicazioni mineralogico- petrografiche per l'ambiente ed i beni culturali
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze botaniche, ecologiche e geologiche
001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:Wiley
eISSN:2042-7158
Copyright Holders:© 2011 The Authors, JPP © 2011 Royal Pharmaceutical Society
Deposited On:18 Nov 2011 10:23

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