Effect of Diabetes on Transscleral Delivery of Celecoxib

• Published in: Pharmaceutical research 2009-02, Vol.26 (2), p.404-414
• Main Authors: Cheruvu, Narayan P. S, Amrite, Aniruddha C, Kompella, Uday B
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood Glucose - metabolism; Blood-Retinal Barrier - metabolism; blood-retinal-barrier; Body Weight; Capillary Permeability; Celecoxib; Cornea - metabolism; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - blood; Cyclooxygenase Inhibitors - pharmacokinetics; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - metabolism; Diabetic Retinopathy - etiology; Diabetic Retinopathy - metabolism; Drug delivery systems; Eyes & eyesight; General pharmacology; Lens, Crystalline - metabolism; Male; Medical Law; Medical sciences; Nonsteroidal anti-inflammatory drugs; periocular injection; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; pigmentation; Pyrazoles - administration & dosage; Pyrazoles - blood; Pyrazoles - pharmacokinetics; Rats; Rats, Inbred BN; Rats, Sprague-Dawley; Research Paper; Retina; Rodents; Sclera - metabolism; Species Specificity; Sulfonamides - administration & dosage; Sulfonamides - blood; Sulfonamides - pharmacokinetics; transscleral; Vitreous Body - metabolism
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9757-2

Purpose To investigate the effects of diabetes on transscleral retinal delivery of celecoxib in albino and pigmented rats. Methods Albino (Sprague Dawley--SD) and pigmented (Brown Norway--BN) rats were made diabetic by a single intraperitoneal injection of streptozotocin (60 mg/kg) following 24 h of fasting and diabetes was confirmed (blood glucose >250 mg/dL). Two months after diabetes induction, the integrity of blood-retinal-barrier in control versus diabetic rats from both strains was compared by using FITC-dextran leakage assay. Fifty microliter suspension of celecoxib (3 mg/rat) was injected periocularly in both the strains in one eye, 2 months following diabetes induction. The animals were euthanized at the end of 0.25, 0.5, 1, 2, 3, 4, 8, and 12 h post-dosing and celecoxib levels in ocular tissues and plasma were estimated using a HPLC assay. Results Diabetes (2-month duration) resulted in 2.4 and 3.5 fold higher blood-retinal barrier leakage in diabetic SD and BN rats, respectively, compared to controls. The area under tissue celecoxib concentration versus time curves (AUC) for sclera, cornea, and lens were not significantly different between control and diabetic animals. However, retinal and vitreal AUCs of celecoxib in treated eyes were approximately 1.5-fold and 2-fold higher in diabetic SD and BN rats, respectively, as compared to the controls. Conclusions Transscleral retinal and vitreal delivery of celecoxib is significantly higher in diabetic animals of both strains. The increase in retinal delivery of celecoxib due to diabetes is higher in pigmented rats compared to albino rats. Higher delivery of celecoxib in diabetic animals compared to control animals can be attributed to the disruption of blood-retinal barrier due to diabetes.