NANOEMULSION AS A NOVEL OPHTHALMIC DELIVERY SYSTEM FOR ACETAZOLAMIDE

Objective: The aim of this work was to formulate the antiglaucoma drug acetazolamide as ocular nanoemulsion of high therapeutic efficacy and prolonged effect. Methods: Eighteen nanoemulsion formulaions consisting of different oils, surfactants and cosurfactants at various ratios and constant water content (39%) were prepared based on their constructed pseudoternary-phase diagrams. According to the In vitro release studies, three nanoemulsions which exhibited fast drug release were used to prepare acetazolamide nanoemulsions with higher water content (59%). The six nanoemulsions at either water content (39 or 59%) were evaluated for their physicochemical properties and ex- vivo corneal permeability. In addition, Draize rabbit eye irritation test was performed. Moreover, biological evaluation of acetazolamide nanoemulsions for their intraocular pressure lowering activity on glaucomatous albino rabbits was carried out. Results: Isopropyl myristate nanoemulsion prepared with cremophor EL and transcutol P exhibited the fastest drug release among all isopropyl myristate nanoemulsions. Oleic acid nanoemulsion prepared with mixture of tween 80 and cremophor EL as surfactants together with transcutol P showed the fastest drug release among other oleic acid nanoemulsion formulae. Similar results were also observed for peanut oil nanoemulsions. The above mentioned formulations either at 39% or 59% water content showed acceptable physicochemical properties and higher acetazolamide permeability coefficient through goat corneas than that reported for the free drug. They also were non irritant to rabbit eye. Therapeutic efficacy testing revealed that peanut oil nanoemulsion at 39% water content showed better and prolonged intraocular pressure lowering effect relative to either commercial brinzolamide eye drops (Azopt®) or the commercial oral acetazolamide tablet (Cidamex®). Conclusion: Acetazolamide was successfully formulated in nanoemulsion form which revealed high therapeutic efficacy in treatment of glaucoma together with a prolonged effect

Microporation-Mediated Transdermal Delivery of In Situ Gel Incorporating Etodolac-Loaded PLGA Nanoparticles for Management of Rheumatoid Arthritis

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and −6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and −23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day)

Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt

Classic galactosemia is caused by deficiency of galactose-1-phosphate uridylyltransferase (GALT). It causes serious morbidity and mortality if left untreated. Screening for galactosemia is not included in Egyptian neonatal screening program. The study aimed to define clinical presentation and complications of galactosemia at Pediatric Hepatology Clinic, Cairo University, Egypt. Thus, the clinical presentation, course and outcome of 37 children with documented galactosemia was studied. Jaundice was the main presentation (67.6%). Other presentations included; convulsions (29.7%), motor retardation (24.3%), mental retardation (5.4%), microcephaly (5.4%), failure to thrive (16.2%), hepatomegaly (62.2%), splenomegaly (35.1%), vomiting (16.2%), diarrhea (8.1%), liver cell failure (10.8%), renal tubular acidosis (5.4%), cataract (5.4%), autoimmune hepatitis (2.7%), self-mutilation (2.7%), combined immune deficiency (2.7%) and kernicterus (2.7%). There was no correlation of residual enzyme activity to severity, clinical presentation, liver function tests, liver biopsy findings or outcome apart from highly significant correlation with repeated chest infections (P = 0.001). Duration to diagnosis and exposure to galactose in diet correlated with liver pathology severity i.e. hepatocyte necrosis (P = 0.003) and cytoskeleton damage (P = 0.003), but not to outcome. Galactosemia should be suspected in any child with liver, neurologic disease and/or immunodeficiency. Its complications are potentially preventable. Early detection is mandatory to prevent serious morbidity and mortality. Initiation of neonatal screening for galactosemia in Egypt is recommended. Keywords: Classic galactosemia, Galactose-1-phosphate uridylyltransferase GALT, Convulsions motor retardation mental retardation, Kernicterus microcephaly, Liver cell failure autoimmune hepatitis, Cataract self-mutilation combined immune deficienc