Chitosan-based nanostructures: A delivery platform for ocular therapeutics ☆ Maria de la Fuente b , Manuela Raviña a , Patrizia Paolicelli a , Alejandro Sanchez a , Begoña Seijo a , Maria Jose Alonso a, ⁎ a Department of Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Faculty of Pharmacy, Campus Sur, 15782 Santiago de Compostela, Spain b Department of Pharmaceutical and Biological Chemistry, University of London, The School of Pharmacy, WC1 1AX London, UK abstract article info Article history: Received 1 July 2009 Accepted 10 November 2009 Available online 1 December 2009 Keywords: Chitosan Ocular Ophthalmics Drug delivery Gene delivery Hyaluronan Nanocapsules Nanoparticles Nanostructures Emulsions Nanoscience and nanotechnology has caused important breakthroughs in different therapeutic areas. In particular, the application of nanotechnology in ophthalmology has led to the development of novel strategies for the treatment of ocular disorders. Indeed, the association of an active molecule to a nanocarrier allows the molecule to intimately interact with specific ocular structures, to overcome ocular barriers and to prolong its residence in the target tissue. Over the last decade, our group has designed and developed a delivery platform based on the polysaccharide chitosan, which suits the requirements of the topical ocular route. These nanosystems have been specifically adapted for the delivery of hydrophilic and lipophilic drugs and also polynucleotides onto the eye surface. The results collected up until now suggest the potential of this delivery platform and the subsequent need of a full preclinical evaluation in order to satisfy the specific regulatory demands of this mode of administration. © 2009 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 2. Critical barriers in ocular therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 2.1. Critical barriers for classical low molecular weight compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 2.1.1. Lipophilic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103 2.1.2. Hydrophilic drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 2.2. Critical barriers for gene-based therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 3. Chitosan solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 4. Chitosan-based delivery vehicles for small molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106 4.1. Chitosan-based nanoemulsions and nanocapsules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 4.2. Chitosan coated nanocapsules and nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 4.3. Chitosan nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 4.4. Chitosan/cyclodextrin nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 5. Chitosan-based delivery vehicles for gene therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 5.1. Chitosan–DNA complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 5.2. Chitosan nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 5.3. Chitosan/hyaluronic acid nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 5.4. Chitosan/alginate nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 5.5. Chitosan–lipid complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 6. Biodistribution, toxicity and biocompatibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 6.1. Biodistribution: interaction of Chitosan-based nanoparticles with the ocular epithelia . . . . . . . . . . . . . . . . . . . . . . . . 111 Advanced Drug Delivery Reviews 62 (2010) 100–117 ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on “Chitosan-Based Formulations of Drugs, Imaging Agents and Biotherapeutics”. ⁎ Corresponding author. Tel.: +34 981 563100(14885); fax: +34 981 547148. E-mail address: mariaj.alonso@usc.es (M.J. Alonso). 0169-409X/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.addr.2009.11.026 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr