title: Clotrimazole nanoemulsion for malaria chemotherapy. Part II: stability assessment, in vivo pharmacodynamic evaluations and toxicological studies.
abstract: The aim of present investigation was to evaluate the potential of clotrimazole as antimalarial drug. Due to poor aqueous solubility and high lipophilicity, it was previously formulated in a nanoemulsion based system. The intrinsic effects of nanoemulsion on improvement of antimalarial activity of clotrimazole were assessed in mice infected with Plasmodium berghei and compared to its suspension formulation. In four-day suppressive test, mice treated with 10mg/kg clotrimazole nanoemulsion showed the highest suppression of parasitemia and; parasitemia was significantly lower than that of 10mg/kg clotrimazole suspension. In onset of activity and recrudescence test, percent reduction of parasitemia was significantly higher in 10 and 15 mg/kg clotrimazole nanoemulsion groups compared to 15 mg/kg suspension group. In both murine models, survival of mice treated with nanoemulsion was significantly prolonged compared to suspension at equivalent doses. The inhibition of parasite growth by clotrimazole in the nanoemulsion was dose dependent as determined by test for linear trend. In repeated dose oral toxicity, levels of serum liver enzymes and biomarkers of hepatotoxicity did not vary significantly from control. Six-month stability testing of the clotrimazole nanoemulsion exhibited no changes in various physiochemical attributes of drug product compared to initial analysis.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400019, Maharashtra, India. vivekborhade@gmail.com
authors.forename: Vivek
authors.initials: V
authors.lastname: Borhade
authors.forename: Sulabha
authors.initials: S
authors.lastname: Pathak
authors.forename: Shobhona
authors.initials: S
authors.lastname: Sharma
authors.forename: Vandana
authors.initials: V
authors.lastname: Patravale
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D003022:Clotrimazole / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D004195:Disease Models, Animal; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006813:Humidity; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D010962:Plasmodium berghei; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013696:Temperature
chemical_list: D000962:Antimalarials; D004655:Emulsions; D005079:Excipients; D003022:Clotrimazole