Polycarboxylic acid nanoparticles for ophthalmic drug delivery: an ex vivo evaluation with human cornea.

In ophthalmic drug delivery, a major problem is retaining an adequate concentration of a therapeutic agent in the pre-corneal area. Polycarboxylic acid carriers such as polyacrylic acid and polyitaconic acid in sub-colloidal, nanoparticulate hydrogel form have a strong potential for sustained release of a drug in ocular delivery. Formulations have been prepared of brimonidine loaded in polycarboxylic (polyacrylic and polyitaconic) acid nanoparticles for potential ophthalmic delivery. These particles were prepared by a reverse micro-emulsion polymerization technique with sizes in the range of 50 nm. The loading efficiencies of the drug brimonidine in the particles were shown to be between 80-85% for polyacrylic acid nanoparticles and between 65-70% for polyitaconic nanoparticles. The loading efficiency was also found to be pH dependent. In a preliminary biocompatibility test, human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability, whereas polyitaconic acid nanoparticles were found to be toxic. Two-photon laser scanning microscopic studies of the fluorescently labelled polyacrylic acid nanoparticles and human cornea shows that they are adhesive on the corneal surface. The polyacrylic acid nanoparticles demonstrated a controlled release of the opthalmological drug (Brimonidine) through the human cornea as compared to that of the commercial formulation, Alphagan.

Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery.

In ocular drug delivery, a major problem is providing an adequate concentration of a therapeutic agent in the precorneal area. Mucoadhesive carriers such as polyacrylic acid in sub-colloidal, nanoparticulate form, have a strong potential for ophthalmic drug delivery. A formulation of brimonidine loaded in polyacrylic acid nanoparticles has been prepared for potential delivery in ophthalmic therapy. The particles were prepared by a reverse microemulsion polymerization technique and their sizes were in the range of 50 nm. In a preliminary biocompatibility test, Caco-2 cells (human primary colonic tumour adenocarcinoma) and human corneal epithelial cells incubated with polyacrylic acid nanoparticles were found to retain their viability over varying times. The loading efficiency of the drug brimonidine in the particles was shown to be between 80-85% and pH dependent. The bioadhesive polyacrylic hydrogel nanoparticles, used in the present study, exhibited superior loading properties for brimonidine, and the formulation was stable for more than 5 weeks. When the drug-loaded nanoparticles were dispersed in a phosphate buffer saline (pH = 7.4), the drug was slowly released over several hours. Two-photon laser scanning microscopic studies of dye-conjugated polyacrylic acid nanoparticles demonstrated the accumulation of the particles on the surface and intercellular spaces of Caco-2 cells.

The application of radionuclide ventriculography to cardiac screening.

Screening asymptomatic individuals for latent coronary disease often requires sequential testing because exercise electrocardiography typically produces more false positive than true positive results in a population with a low prevalence of coronary disease. Cardiac scintigraphy is a technique that may be employed as a confirmatory test in lieu of coronary arteriography to further evaluate the significance of a positive exercise electrocardiogram. Radionuclide ventriculography was employed in 98 asymptomatic individuals who were considered to be at moderate risk of heart disease after risk factor analysis and exercise electrocardiography. Seventeen (17%) patients had an abnormal study and underwent cardiac catheterization. Seven had coronary artery disease, two had cardiomyopathy, and eight were normal. Eighty-one (83%) patients had a normal study. Because the sensitivity of radionuclide ventriculography is 63-80%, it was postulated that 2 to 5 individuals with disease were missed. Thus, from a population with an 11-14% prevalence of disease, two subsets were identified. A large subset in which a prevalence of 2-6% could be estimated was separated from a much smaller one in which a prevalence of approximately 50% was demonstrated.

Respiratory depression following retrobulbar bupivacaine: three case reports and literature review.

Retrobulbar bupivacaine (0.75%) administration has been implicated as a causative factor in respiratory distress, cardiovascular dysfunction, and various central nervous system disturbances. The three cases here demonstrate two separate occurrences of respiratory and central nervous system (CNS) complications following retrobulbar bupivacaine (Marcaine) injection. It is thought that the immediate and delayed occurrences result from inadvertent injection at either of two sites: intravascularly or directly into the membranous sheath surrounding the optic nerve.

The use of FEIBA (factor eight inhibitor bypassing activity) in cataract extraction in hemophilia A patient with inhibitor.

A 34-year-old patient, with severe factor VIII deficiency (anti-hemophilic factor deficiency) and inhibitor against factor VIII, underwent a phacoemulsification with posterior capsulatomy and thermal iridectomy under general anesthesia. FEIBA (Factor Eight Inhibitor Bypassing Activity) was used to achieve hemostasis. The surgical procedure was successful and no complication was ensued. A brief management of hemophilia A patient requiring surgery is discussed.