ABSTRACT
Two different chitosan (CS) nanocarriers namely nanoparticles and nanoemulsion were developed to prolong Indomethacin (IM) precorneal residence time and to improve its ocular bioavailability the main limitations in its management of post-operative inflammation and intraocular irritation after cataract extraction. CS-nanoparticles were developed by modified ionic gelation of CS with tripolyphosphate while nanoemulsion was prepared by spontaneous emulsification technique. Transmission electron microscopy revealed regular well-identified spherical shape. The nanoparticles had a mean size of 280 nm, a zeta potential of + 17 mV and high loading efficiency of 84.8 % while the mean size of nanoemulsion was affected by the nature of the surfactant used and varies between 220-690 nm. In vitro release studies, performed under sink conditions, revealed small initial burst release during the first hour followed by slow gradual drug release of 76 and 86% from nanoparticles and nanoemulsion respectively during a 24 h period. In vivo studies and histopathological examination revealed that eyes of rabbits treated with nanoemulsion showed clearer healing of corneal chemical ulcer with moderate effective inhibition of polymorph nuclear leukocytic infiltration (PMNLs) compared with nanoparticles preparation. Moreover, following topical instillation of CS-nanoemulsion to rabbits, it was possible to achieve therapeutic concentration of IM in the cornea through out the duration of the study and fairly high IM level in inner ocular structure, aqueous humor. These levels were significantly higher than those obtained following instillation of IM solution. Therefore, CS nanocarriers developed in this study were able to contact intimately with the cornea providing slow gradual IM release with long-term drug level thereby increasing delivery to both external and internal ocular tissues.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Chitosan/chemistry , Indomethacin/administration & dosage , Nanoparticles/administration & dosage , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aqueous Humor/metabolism , Area Under Curve , Chemical Phenomena , Chemistry, Physical , Cornea/metabolism , Drug Delivery Systems , Drug Stability , Emulsions , Excipients , Indomethacin/pharmacokinetics , Indomethacin/therapeutic use , Keratitis/drug therapy , Keratitis/pathology , Male , Microscopy, Electron, Transmission , Ophthalmic Solutions , Particle Size , Powders , Rabbits , Reference Standards , SolutionsABSTRACT
BACKGROUND: The study evaluates whether Optison used during dobutamine stress echocardiography (DSE) will improve endocardial border definition and whether this will translate to an improvement in sensitivity and specificity of the test in patients with poor echocardiographic windows. DSE is extremely valuable in the workup of patients with coronary artery disease. The test is limited in patients with suboptimal endocardial border visualization. Frequent studies have demonstrated improved endocardial border visualization with intravenous contrast agents at rest. METHODS AND RESULTS: We studied 229 patients: 112 had good rest echocardiography with no contrast and 117 had poor rest echocardiography with Optison injection during DSE. Percentage of endocardial border visualization, wall thickening, sensitivity, and specificity were compared in both groups, as was interobserver variability. Both groups were matched with respect to age, percentage of previous myocardial infarctions, resting wall motion abnormality, percentage of coronary stenosis, and number of diseased coronary arteries. Optison significantly improved endocardial border visualization, especially at peak stress. The ability to measure wall thickening was significantly higher in the contrast DSE group with suboptimal images versus the noncontrast group with optimal images (89% ability to measure wall thickening vs 71%, P =.01). This resulted in a comparable sensitivity (79% vs 71%, P = not significant [NS]), specificity (76% vs 82%, P = NS), and diagnostic accuracy (80% vs 76%, P = NS). Agreement on test interpretation was higher among 3 observers in contrast DSE versus noncontrast DSE groups (79% vs 69%, P =.01). CONCLUSIONS: In patients with poor echocardiographic windows, the use of Optison during DSE improves endocardial border visualization, which translates to a comparable sensitivity and specificity to noncontrast DSE tests in patients with good echocardiographic windows.
