Ocular Surface in vivo Tolerance to New Nanoparticulate Polymer Systems Designed for Drug Delivery

Ocular Surface in vivo Tolerance to New Nanoparticulate Polymer Systems Designed for Drug Delivery
2005
Y. Diebold1, A. Enr?quez de Salamanca1, M. Calonge1, A. Vila2, E.L. S. Carvalho2, M. de la Fuente2, B. Seijo2 and M.J. Alonso2
Investigative Ophthalmology & Visual Science
1 IOBA?University of Valladolid, Valladolid, Spain
2 Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela, Santiago de Compostela, Spain
Commercial Relationships: Y. Diebold, None; A. Enr?quez de Salamanca, None; M. Calonge, None; A. Vila, None; E.L.S. Carvalho, None; M. de la Fuente, None; B. Seijo, None; M.J. Alonso, None.
Support: FEDER?CICYT MAT2003?09713?C02?01 and MAT2004?04792?C02?01, Ministry of Science, Spain.
Abstract
Purpose: To evaluate the in vivo acute tolerance of ocular surface structures to new classes of nanoparticulate colloidal systems previously developed and tested in vitro by our group and designed as potential drug delivery systems for ocular administration.
Methods: Three different nanoparticulate systems were prepared by ionotropic gelation, followed by freeze drying in the presence of 5.0 % trehalose, and carrying bovine serum albumin as a marker molecule: chitosan?based nanoparticles (CH?NPs), hyaluronic acid?based nanoparticles (HA?NPs) and lipids?chitosan nanoparticle complexes (LNPs). In vivo acute tolerance of 0.5 mg/ml CH?NPs, HA?NPs and LNPs was studied in 15 female albino rabbits. Each formulation was instilled in OD every 30 minutes, for a total of 13 times, leaving OS untouched as a control. Clinical signs were evaluated previously and 3, 6, and 24 h after the first instillation and statistically analyzed using the Fisher?s exact test. Conjunctival impression cytology (CIC), collected 6 days before starting and 24 h after the first instillation, were done in all animals. Ocular structures were removed, fixed and processed for a pathology study. Experiments were performed in a masked fashion.
Results: Neither irritation nor damage was observed in vivo after ocular surface exposure to any class of nanoparticles and complexes. CIC showed normal characteristics related to size and distribution of goblet cells and N/C ratio. Ocular surface epithelia were not altered and lid tissues had no signs of edema or inflammation. Inflammatory cells were basically absent, although some scattered polymorphonuclear cells, also present in control eyes, were seen.
Conclusions: Tested CH?NPs, HA?NPs and LNPs were well tolerated and the ocular surface tissues remained normal after in vivo exposure. These results, along with previous results showing virtually no in vitro toxicity, add further support to the potential use these nanoparticulate systems as drug carriers to treat ocular surface disorders.
Key Words: conjunctiva ? cornea: epithelium ? cornea: tears/tear film/dry eye
? 2005, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. For permission to reproduce any part of this abstract, contact the ARVO Office at arvo@arvo.org.