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.

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Abbreviations

IVM:

Ivermectin

DEC:

Diethylcarbamizine

mf:

Microfilaria

CS:

Chitosan

ALG:

Alginate

CS–ALG NPs:

Chitosan–alginate nanoparticles

MIF activity:

Microfilaricidal activity

MAF activity:

Macrofilaricidal activity

TEM:

Transmission electron microscopy

DLS:

Dynamin light scattering

FT-IR:

Fourier-transform infrared

DSC:

Differential scanning calorimetry

AUC:

Area under the concentration–time curve

C max :

Maximum concentration

MRT:

Mean residence time

T max :

Time to peak concentration

%EE:

percent entrapment efficiency

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Acknowledgments

The authors are thankful to Indian Council of Medical Research (ICMR), New Delhi, India for providing financial support in the form of Senior research fellowships to M.A. and M.V.

Declaration of Interest

The authors report no declarations of interest.

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Correspondence to Mohammad Ali.

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Ali, M., Afzal, M., Verma, M. et al. Improved antifilarial activity of ivermectin in chitosan–alginate nanoparticles against human lymphatic filarial parasite, Brugia malayi . Parasitol Res 112, 2933–2943 (2013). https://doi.org/10.1007/s00436-013-3466-4

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Keywords

  • Drug Loading
  • Ivermectin
  • Entrapment Efficiency
  • Lymphatic Filariasis
  • Polymeric Nanoparticles