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Comparative studies of various hyaluronic acids produced by microbial fermentation for potential topical ophthalmic applications
Author(s) -
Guillaumie Fanny,
Furrer Pascal,
FeltBaeyens Olivia,
Fuhlendorff Birgit L.,
Nymand Søren,
Westh Peter,
Gurny Robert,
SchwachAbdellaoui Khadija
Publication year - 2009
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.32481
Subject(s) - hyaluronic acid , materials science , differential scanning calorimetry , filtration (mathematics) , chromatography , biomedical engineering , chemistry , medicine , statistics , physics , mathematics , anatomy , thermodynamics
Abstract This work presents a comparative study of various hyaluronic acids (HA) produced by fermentation of either Bacillus subtilis or Streptococcus towards the selection of an optimal molecular weight (MW) HA for the preparation of topical ophthalmic formulations. The influence of HA MW on water binding capacity, sterile filtration, rheological properties, precorneal residence time and ocular tolerance of ophthalmic solutions was investigated. Molecular weight did not affect hydration of hyaluronic acid according to differential scanning calorimetry (DSC). In general, medium MW HA (0.6–1 MDa) resulted in solutions that were superior in terms of sterile filtration and kinematic viscosity requirements compared to high MW HA (>1 MDa). Moreover, all HA‐based solutions exhibited well‐defined viscoelastic properties that depend on MW. Gamma scintigraphic data indicated that HA MW at 0.1% concentration (w/v) and HA origin did not significantly affect the corneal residence time on rabbit eyes. A 0.3% solution of high MW HA had a prolonged residence time in the precorneal area compared to a medium MW HA at the same concentration. Finally, an in vivo ocular irritation test based on confocal laser scanning ophthalmoscopy (CLSO) conclusively showed the excellent tolerance of both Bacillus ‐derived HA and Streptococcus ‐derived HA after topical instillation onto the corneal surface. Overall, this comprehensive work highlights the superiority of medium MW hyaluronic acid for topical ophthalmic formulations based on their physico‐chemical and biological properties, tolerance and handling. Such solutions are expected to enhance tear film stability, to allow for maximum comfort, and to exhibit high residence times, while being biocompatible and easy to sterile filter. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010