Showing papers by "Roop K. Khar published in 2015"
TL;DR: Highly mono-disperse spherical and rod-shaped silver nanoparticles synthesized using reverse microemulsion and aqueous phase methods have a promising potential as to lower the toxicity of Ag NPs.
Abstract: In the present study, toxicity of nanoparticles is evaluated for assessing their effect on liver and kidney. We have synthesized highly mono-disperse spherical and rod-shaped silver nanoparticles using reverse microemulsion and aqueous phase methods. These were characterized by UV-vis spectrophotometer, dynamic light scattering, and transmission electron microscope confirming the formation of different sizes of spherical-shaped and rod-shaped silver nanoparticles (Ag NPs). Acute toxicity of different shapes and sizes of Ag NPs and their modulations by using Withania somnifera were evaluated through biochemical and histopathological changes in liver and kidney tissues of Wistar rats. We also evaluated cytotoxicity in specific murin macrophages through confocal microscopy. Cytotoxicity analysis indicates that median lethal dose (LD50) for 20, 50, and 100-nm size spherical and 100-nm rod-shaped Ag NPs was 0.25, 0.35, 0.35, and 0.35 mg/ml, respectively. We also calculated clinically important protein concentration to illustrate the efficacy of Ag nanomaterials. These studies indicated that 20, 50, and 100-nm spherical Ag NPs (35 mg/kg, 23 days) increased the biochemically important enzymes and substrate levels glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), creatinine, and urea concentration in serum, showing liver and kidney tissue damage. After 23 days of treatment of Ag NPs (20, 50, and 100 nm spherical), along with W. somnifera, toxicity of Ag NPs significantly decreased and marginalized. However, no significant changes were observed for 100-nm rod-shaped Ag NPs on normal liver and kidney architecture. Given their low toxic effects and high uptake efficiency, these have a promising potential as to lower the toxicity of Ag NPs.
14 citations
TL;DR: The results indicate that oral drug treatment of irinotecan in presence of temporary P-gp inhibition could be as equally safe and effective as intravenous administration.
Abstract: We have recently demonstrated that the oral bioavailability of irinotecan (80 mg/kg) can be increased at least 7-fold by co-administration of the P-gp blocker verapamil (25 mg/kg, Oral). As a result, co-treatment with P-gp inhibitor could be a useful strategy for bioavailability enhancement. However, in view of narrow therapeutic index, the co-administration of irinotecan and verapamil may result in unanticipated toxicities. Therefore, dose optimisation studies of irinotecan were performed when it is given in conjunction with a P-gp inhibitor. For dose optimization study, the bioavailability and pharmacokinetic parameters were studied in rats after oral administration of irinotecan at three doses (i.e. 20, 40 and 80 mg/kg) alone and in combination with verapamil (25 mg/kg, oral). The area under the plasma-concentration time curve (AUC) of irinotecan at 20, 40 and 80 mg/kg was 3.51 ± 1.20, 8.81 ± 1.93 and 14.03 ± 2.18 h µg/ml, respectively which after treatment with verapamil, increased dose dependently to 7.84 ± 1.20, 19.94 ± 2.39 and 61.71 ± 15.0 h µg/ml, respectively. In addition to irinotecan, plasma concentrations of SN-38, one of the major active metabolite of irinotecan, were also monitored. The less than proportional increase in SN-38 AUC from 20 to 80 mg/kg is consistent with the saturation of carboxylesterase. Our results indicate that oral drug treatment of irinotecan in presence of temporary P-gp inhibition could be as equally safe and effective as intravenous administration. Nevertheless, safe P-gp inhibitors need to be identified as alternatives to verapamil for development of efficacious oral irinotecan formulations.
2 citations