Background: Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis. Purpose: The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration. Methods: NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box-Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X 1 ], surfactant concentration [X 2 ], and sonication frequency [X 3 ]) on particle size (R 1), zeta potential (ZP; R 2), and drug entrapment efficiency (EE%) (R 3) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated. Results: The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (P app) and steady-state flux (J ss) reached 11.59×10-2 cm h-1 and 3.94 mol h-1 , respectively, in comparison with 7.28×10-2 cm h-1 and 2.48 mol h-1 for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against Aspergillus fumigatus ATCC 1022 and a Candida albicans clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate , that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues. Conclusion: Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.

No abstract

Several derivatives containing the thieno [2,3-d]pyrimidine system were prepared starting from 2-amino-4,5-dihydronaphtho[2,1-b]thiophene-1-carbonitrile (1). In particular, the synthesis and structure characterization of 8,9-dihydronaphtho-[1 ,2 :4,5]thieno [3,2-e] [1,2,4]triazolo [4,3-c]pyrimidine derivatives 13-16 and their isomerization to 8,9-dihydronaphtho[1 ,2 :4,5]thieno [3,2-e]

Keywords: Amidoalkylation / Trichloroacetimidate / Synthesis / Indolizidines / Glycosidase Inhibitor / Lentiginosine N-α-Hydroxyalkylamides 6a,b, readily available from L-tartrate, with trichloroacetonitrile furnish O-(2-oxopyrrolidin-5-yl)trichloroacetimidates 3a,b. α-Amido-alkylation studies of 3a,b with allyl-trimethylsilane and electron-rich benzene derivatives as C-nucleophiles afforded 5-allyl-and 5-aryl-2-pyrrolidinones 2a,b, 7a,b, and 8−10. The target compound

A series of 2-methyl-N-substituted-benzimidazoles, bearing hydroxypyrrolidinon-5-yl or hydroxypyrrolidin-2-yl, 2,3:5,6-di-O-isopropylidene--D-mannofuranoside, 2,3,5,6-tetrahydroxy--D-mannofuranoside, 1:2,5:6-di-O-isopropylidene--D-gluco-furanose,3-O-benzyl-6,7-dideoxy-1:2-O-isopropylidene--D-xylo-heptofuranos-5-ulose, 3-O-benzyl-6,7-dideoxy-1,2-dihydroxy--D-xylo-heptofuranos-5-ulose, 1,2,5,6-tetrahydroxy--D-glucofuranose sugar moieties, were obtained in good yields from 2-methyl N-(trichloroacetamidomethyl)benzimidazole as a donor and carbohydrate residues as acceptor precursors in the presence of catalytic amount of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as Lewis acid. Compounds 6, 7, 10, 13, 15, and 16 showed significant anti-inflammatory and analgesic activities.

No abstract

No abstract

No abstract