Evaluation of cyclosporine A eye absorption after administration of liposomal or conventional forms in animal model

A lot of researches have investigated the effects of topical cyclosporine A on the eye surface layers' diseases. By now the main limitation in cyclosporine application is the low permeation of the drug into the posterior segments of the eye. The aim of present study was to formulate high permeable dosage form can be beneficial in the topical treatment of the uveitis. To reach higher corneal drug absorption and drug concentration in the posterior segments of the eye, 3 nanoliposomal formulations containing 0.5 mg/ml cyclosporine A were prepared. Liposomal formulations and the commercial product [Restasis] were instilled in the right and left eyes of the rabbits, respectively. The rabbits were killed in the 3, 7, 14 and 28 days of study and the aqueous humor and vitreous were extracted. Mean size of liposomal formulation number 1, number 2 and number 3 were 107.2 +/- 0.7, 129.3 +/- 0.9 and 144.8 +/- 1.8 nm and their zeta potential were -5.0 +/- 1.7, -5.5 +/- 2.3 and 44.6 +/- 6.2 mV, respectively. Results of ocular analysis showed that the liposomal formulations could increase the concentration of the drug in the aqueous and vitreous like Restasis. But, in contrast with what has been expected the findings of this study implicate nanoliposomal formulations prepared could not make a significant difference in concentration of the drug in aqueous and vitreous humor compared to Restasis [anionic microemulsion]. In conclusion, we can state that liposomes with the same composition as our formulations are not more efficient than microemulsion for cyclosporine as ophthalmic drug delivery

Synthesis of novel 4-[l-[4-fluorobenzyl]-5-imidazolyl] dihydropyridines and studying their effects on rat blood pressure

Calcium-channel Mockers have an important role in the treatment of several cardiovascular disorders. Derivatives of 1, 4-dihydropyridine are one of the most potent calcium antagonists. In this study four novel 1, 4-dihydropyridine calcium channel blockers were synthesized and their hypotensive properties were investigated in male rats. Four 1, 4-dihydropyridines bearing l-[4-fluorobenzyl]-54midazoIyl substituent at 4 position [5a-d] were synthesized and tested for hypotensive activity in male rats. The animal was anaesthetized and the right jugular vein was cannulated for the administration of test agents. The left carotid artery was cannulated and connected to a pressure transducer for continuous monitoring of arterial blood pressure. All synthesized compounds lowered rat blood pressure significantly in comparison with DMSO as vehicle and nifedipine as positive control. The hypotensive effects of all compounds were less than that of nifedipine at 2 and 4 mg/kg [P< 0.05]. The order of their effects on mean arterial blood pressure [MABP] was 5b>5c>5a>5d at dose of 4 mg/kg [P< 0.05]. All compounds tested increased heart rate in comparison with DMSO [P< 0.05]. The chronotropic effect of nifedipine was significantly less than synthesized compounds at dose of 4 mg/kg [P< 0.01]. The results showed that these novels 1, 4-dihydropyridines decreased mean arterial blood pressure [MABP] significantly, while increased heart rate in rat