title: Improved antifilarial activity of ivermectin in chitosan-alginate nanoparticles against human lymphatic filarial parasite, Brugia malayi.
abstract: The current antifilarial treatments are not up to the mark partly due to deep location of filarial parasites in the human lymphatic system. We report here on the improvement in the antifilarial activity of ivermectin (IVM) using chitosan-alginate nanoparticles prepared by modified complex coacervation method. The nanoparticles were spherical having 155 nm size and 4.56 and 75.67% loading and entrapment efficiency respectively for IVM. The delivery system maintained the sustained release and significantly augmented the microfilaricidal (MIF) activity at a single low dose (200 μg/kg body weight, subcutaneously) in contrast to much higher dose of free ivermectin (400 μg/kg body weight, subcutaneously) against human lymphatic filariid, Brugia malayi in rodent host, Mastomys coucha. To substantiate increase in MIF activity, pharmacokinetics study was designed on Wistar rats which revealed a greater peak plasma concentration (45.3 ± 1.79 ng/ml), area under the concentration curve (298 ± 38.7 ng d/ml) and extended mean residence time (23.4 ± 8.56 days)of IVM in chitosan-alginate nanoparticles. Administration of 25 mg/kg of diethylcarbamazine following nanoparticle therapy significantly improved the MIF and macrofilaricidal action of encapsulated drug and was considered superior in this study.
authors.affiliation: Hamdard Nanobiotechnology Center for Advance Research, Faculty of Engineering & Interdisciplinary Sciences, Hamdard University (Jamia Hamdard), New Delhi, India. mohd.ali.hamdard@gmail.com
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.forename: Mohammad
authors.initials: M
authors.lastname: Afzal
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Verma
authors.forename: Shailja
authors.initials: S
authors.lastname: Misra-Bhattacharya
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Dinda
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D019540:Area Under Curve; D017178:Brugia malayi / Q000187:drug effects*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D005369:Filaricides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051189:Murinae; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013995:Time
chemical_list: D000464:Alginates; D005369:Filaricides; D006603:Hexuronic Acids; D007559:Ivermectin; D020723:Glucuronic Acid; D048271:Chitosan