A Mucoadhesive Polymer Extracted from Tamarind Seed Improves the Intraocular Penetration and Efficacy of Rufloxacin in Topical Treatment of Experimental Bacterial Keratitis

ABSTRACT Bacterial keratitis is a serious infectious ocular disease requiring prompt treatment to prevent frequent and severe visual disabilities. Standard treatment of bacterial keratitis includes topical administration of concentrated antibiotic solutions repeated at frequent intervals in order to reach sufficiently high drug levels in the corneal tissue to inhibit bacterial growth. However, this regimen has been associated with toxicity to the corneal epithelium and requires patient hospitalization. In the present study, a mucoadhesive polymer extracted from tamarind seeds was used for ocular delivery of 0.3% rufloxacin in the treatment of experimental Pseudomonas aeruginosa and Staphylococcus aureus keratitis in rabbits. The polysaccharide significantly increased the intra-aqueous penetration of rufloxacin in both infected and uninfected eyes. Rufloxacin delivered by the polysaccharide reduced P. aeruginosa and S. aureus in the cornea at a higher rate than that obtained by rufloxacin alone. In particular, use of the polysaccharide allowed a substantial reduction of S. aureus in the cornea to be achieved even when the time interval between drug administrations was extended. These results suggest that the tamarind seed polysaccharide prolongs the precorneal residence times of antibiotics and enhances drug accumulation in the cornea, probably by reducing the washout of topically administered drugs. The tamarind seed polysaccharide appears to be a promising candidate as a vehicle for the topical treatment of bacterial keratitis.

[1]  A. Ludwig,et al.  The use of mucoadhesive polymers in ocular drug delivery. , 2005, Advanced drug delivery reviews.

[2]  L. Laroche,et al.  Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases , 2003, The British journal of ophthalmology.

[3]  R. Cavalli,et al.  Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. , 2002, International journal of pharmaceutics.

[4]  L. Zografos,et al.  Bacterial keratitis: a prospective clinical and microbiological study , 2001, The British journal of ophthalmology.

[5]  S. Burgalassi,et al.  Gel-forming erodible inserts for ocular controlled delivery of ofloxacin. , 2001, International journal of pharmaceutics.

[6]  P. McDonnell,et al.  Bacteriologic and Clinical Efficacy of Ofloxacin 0.3% Versus Ciprofloxacin 0.3% Ophthalmic Solutions in the Treatment of Patients with Culture-positive Bacterial Keratitis , 2001, Cornea.

[7]  H. Taylor,et al.  Increased incidence of corneal perforation after topical fluoroquinolone treatment for microbial keratitis. , 2001, American journal of ophthalmology.

[8]  E. Ghelardi,et al.  Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits. , 2000, The Journal of antimicrobial chemotherapy.

[9]  G. Alexandrakis,et al.  Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones. , 2000, Ophthalmology.

[10]  H. Taylor,et al.  Fluoroquinolone and fortified antibiotics for treating bacterial corneal ulcers , 2000, The British journal of ophthalmology.

[11]  G. Banchelli,et al.  A New Viscosity Enhancer for Ophthalmic Preparations Devoid of Toxicity for Human Conjunctival Cells , 2000 .

[12]  S. Pauluzzi,et al.  Penetration of Rufloxacin into the Cerebrospinal Fluid in Patients with Inflamed and Uninflamed Meninges , 2000, Antimicrobial Agents and Chemotherapy.

[13]  H. Dua,et al.  Antimicrobial defensin peptides of the human ocular surface , 1999, The British journal of ophthalmology.

[14]  S. Burgalassi,et al.  Development of a Simple Dry Eye Model in the Albino Rabbit and Evaluation of Some Tear Substitutes , 1999, Ophthalmic Research.

[15]  K. Mcclellan Mucosal defense of the outer eye. , 1997, Survey of ophthalmology.

[16]  James M. Hill,et al.  Ocular drug delivery: A comparison of transcorneal iontophoresis to corneal collagen shields , 1995 .

[17]  James M. Hill,et al.  Pharmacokinetic Considerations in the Treatment of Bacterial Keratitis , 1994, Clinical pharmacokinetics.

[18]  R. Snyder,et al.  Penetration of topically applied ciprofloxacin, norfloxacin, and ofloxacin into the aqueous humor. , 1994, Ophthalmology.

[19]  J. Hadgraft,et al.  Evaluation of Mucoadhesive Polymers in Ocular Drug Delivery. II. Polymer-Coated Vesicles , 1992, Pharmaceutical Research.

[20]  M. Ligtenberg,et al.  Cell membrane-associated mucins and their adhesion-modulating property. , 1992, Trends in biochemical sciences.

[21]  R. Wise,et al.  The in-vitro activity of two new quinolones: rufloxacin and MF 961. , 1992, The Journal of antimicrobial chemotherapy.

[22]  B. Imbimbo,et al.  Pharmacokinetics and tissue penetration of rufloxacin, a long acting quinolone antimicrobial agent. , 1991, The Journal of antimicrobial chemotherapy.

[23]  A. Oomomo [Pseudomonas aeruginosa ocular infection]. , 1991, Nihon rinsho. Japanese journal of clinical medicine.

[24]  J. Hadgraft,et al.  Evaluation of Mucoadhesive Polymers in Ocular Drug Delivery. I. Viscous Solutions , 1991, Pharmaceutical Research.

[25]  J. A. Hobden,et al.  The role of pneumolysin in ocular infections with Streptococcus pneumoniae. , 1990, Current eye research.

[26]  J. Bosso,et al.  The comparative in vitro activity of ofloxacin and selected ophthalmic antimicrobial agents against ocular bacterial isolates. , 1989, American journal of ophthalmology.

[27]  C. Basbaum,et al.  Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells , 2002, Nature Medicine.

[28]  P. Garg,et al.  Bilateral infectious keratitis after laser in situ keratomileusis: a case report and review of the literature. , 2001, Ophthalmology.

[29]  G. Banchelli,et al.  Effect of Xyfoglucan (Tamarind Seed Polysaccharide) on Conjunctival Cell Adhesion to Laminin and on Corneal Epithelium Wound Healing , 2000, European journal of ophthalmology.

[30]  Sibel Özyazgan,et al.  Penetration of topically applied ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor of the uninflamed human eye. , 1997, Journal of chemotherapy.

[31]  H. Lazarus,et al.  Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity. , 1991, Current eye research.