Chitosan nanoparticles loaded with dorzolamide and pramipexole Sofia Papadimitriou a , Dimitrios Bikiaris a, * , Konstantinos Avgoustakis b , Evangelos Karavas c , Manolis Georgarakis d a Laboratory of Organic Chemical Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece b Laboratory of Pharmaceutical Technology, Department of Pharmacy, University of Patras, Rio 26500, Patras, Greece c Pharmathen S.A., Pharmaceutical Industry, Dervenakion Str., 6, Pallini Attikis, 153 51 Attiki, Greece d Section of Pharmaceutics and Drug Control, Department of Pharmacy, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece Received 25 June 2007; received in revised form 16 October 2007; accepted 2 November 2007 Available online 13 November 2007 Abstract Chitosan (CS) nanoparticles of dorzolamide hydrochloride (Dorzo) and pramipexole hydrochloride (Prami) were prepared by the ionic gelation method and their in vitro properties were studied. The long-term objective is the development of efficient ocular formu- lations for Dorzo and efficient oral formulations for Prami. The particle size of nanoparticles was affected by the CS/drug ratio whereas it was not affected by the type of drug (Dorzo or Prami). Drug association efficiency to the nanoparticles did not appear to correlate with the drug/CS ratio whereas the loading capacity tended to fall with increasing drug proportion. Based on WAXD data, Dorzo was dis- persed in the nanoparticles in crystalline form, probably due to the weak interaction developed between Dorzo and CS/TPP matrix as FT-IR data indicated. In contrast, WAXD and step-scan DSC data indicated that Prami formed a molecular dispersion within the nano- particles. This was probably due to the potent interactions developed between Prami and CS/TPP matrix, as FT-IR data revealed. The nanoparticles exhibited mucoadhesive properties which diminished with increasing drug content. Sustained in vitro drug release was observed with the Dorzo-loaded CS nanoparticles in PBS (pH 7.4) and with the Prami-loaded CS nanoparticles in simulated intestinal fluid. The results obtained in this study suggest that the Dorzo-loaded CS nanoparticles and the Prami-loaded CS nanoparticles could be further evaluated for the controlled ocular delivery of Dorzo and the controlled oral delivery of Prami, respectively. Ó 2007 Elsevier Ltd. All rights reserved. Keywords: Chitosan; Nanoparticles; Ionotropic gelation; Pramipexole; Dorzolamide 1. Introduction CS, a (1-4)2-amino 2-deoxy b-D-glucan, is a deacetylated form of chitin, an abundant polysaccharide present in crus- tacean shells. CS is biocompatible (Hirano & Noishiki, 1985) and, because of its cationic nature, has good muco- adhesive and membrane permeability-enhancing properties (Illum, 1998, 2007). Therefore, CS has been extensively investigated for its potential as absorption enhancer across intestinal epithelium for drugs, peptides, and proteins (Kotez et al., 1997; Lavelle, 2000; Takeuchi, Yamamoto, Niwa, Hino, & Kawashima, 1996; Van der Lubben, Ver- hoef, Borchard, & Junginer, 2001) and for the preparation of various systems for mucosal drug delivery (Cui, Qian, & Yin, 2006; Dodane & Vilivalam, 1998; Kumar, Muzzarelli, Muzzarelli, Sashiwa, & Domb, 2004; Paul & Sharma, 2000; Prego, Garcia, Torres, & Alonso, 2005). Hydrophilic nano- particles based on CS receive currently increasing interest as they could control the rate of drug release, prolonging the duration of the therapeutic effect, and deliver the drug to specific sites in the body (Agnihotri, Mallikarjuna, & Aminabhavi, 2004; Janes, Calvo, & Alonso, 2001; Prabah- aran & Mano, 2005). CS can form nanoparticles using, amongst other methods, ionotropic gelation. The method is based on the gelation of CS when it comes in contact with specific polyanions due to the formation of inter- and intramolecular cross-linkages mediated by these poly- 0144-8617/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbpol.2007.11.007 * Corresponding author. Tel.: +30 2310 997812; fax: +30 2310 997667. E-mail address: dbic@chem.auth.gr (D. Bikiaris). www.elsevier.com/locate/carbpol Available online at www.sciencedirect.com Carbohydrate Polymers 73 (2008) 44–54