Improved antifilarial activity of ivermectin in chitosan–alginate nanoparticles against human lymphatic filarial parasite, Brugia malayi


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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Chitosan–alginate nanoparticles

MIF activity:

Microfilaricidal activity

MAF activity:

Macrofilaricidal activity


Transmission electron microscopy


Dynamin light scattering


Fourier-transform infrared


Differential scanning calorimetry


Area under the concentration–time curve

C max :

Maximum concentration


Mean residence time

T max :

Time to peak concentration


percent entrapment efficiency


  1. Ali DN, Hennessy DR (1996) The effect of level of feed intake on the pharmacokinetic disposition and efficacy of ivermectin in sheep. J Vet Pharmacol Ther 19:89–94

    PubMed  Article  CAS  Google Scholar 

  2. Ali M, Alam S, Ahmad S, Dinda AK, Ahmad FJ (2011) Determination of ivermectin stability by high-performance thin-layer chromatography. Int J Drug Dev Res 3:240–247

    CAS  Google Scholar 

  3. Ali M, Afzal M, Bhattacharya SM, Ahmad FJ, Dinda AK (2013) Nanopharmaceuticals to target antifilarials: a comprehensive review. Expert Opin Drug Deliv 10(5):665–678

    PubMed  Article  CAS  Google Scholar 

  4. Bajpai P, Vedi S, Owais M, Sharma SK, Saxena PN, Misra-Bhattacharya S (2005) Use of liposomized tetracycline in elimination of Wolbachia endobacterium of human lymphatic filariid Brugia malayi in a rodent model. J Drug Target 13(6):375–381

    PubMed  Article  CAS  Google Scholar 

  5. Bajpai P, Srivastava K, Shakya S, Saxena PN, Misra-Bhattacharya S (2007) Improvement in the efficacy of existing combination of antifilarials by inclusion of tetracycline in rodent model of brugian filariasis. Curr Sci 92(5):655–658

    CAS  Google Scholar 

  6. Bassissi F, Lespine A, Alvinerie M (2006) Assessment of a liposomal formulation of ivermectin in rabbit after a single subcutaneous administration. Parasitol Res 98:244–249

    Google Scholar 

  7. Borges FA, Cho HS, Santos E, Oliveira GP, Costan AJ (2007) Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle. J Vet Pharmacol Ther 30(1):62–67

    PubMed  Article  CAS  Google Scholar 

  8. Campbell WC (1993) Ivermectin—an anti-parasitic agent. Med Res Rev 13:61–79

    PubMed  Article  CAS  Google Scholar 

  9. Chen SC, Wu YC, Mi FL, Lin YH (2004) A novel pH-sensitive hydrogel composed of N,O-carboxymethyl chitosan and alginate crosslinked by genipin for protein drug delivery. J Control Rel 96:285–300

    Article  CAS  Google Scholar 

  10. Clark SL, Crowley AJ, Schmidt PG, Donoghue AR, Piché CA (2004) Long-term delivery of ivermectin by use of poly (d,l-lactic-co-glycolic) acid microparticles in dogs. Am J Vet Res 65(6):752–757

    PubMed  Article  CAS  Google Scholar 

  11. Dangi A, Dwivedi V, Vedi S, Owais M, Misra-Bhattacharya S (2010) Improvement in the antifilarial efficacy of doxycycline and rifampicin by combination therapy and drug delivery approach. J Drug Target 18(5):343–350

    PubMed  Article  CAS  Google Scholar 

  12. Fan PC (1994) Determination of the earliest appearance and peak count of microfilariae of Wuchereria bancrofti and Brugia malayi after taking a single dose of diethylcarbamazine at noon. J Helminthol 68(4):301–304

    PubMed  Article  CAS  Google Scholar 

  13. George M, Abraham TE (2006) Polyhydrochloride for intestinal delivery of protein drugs: chitosan and alginate. J Control Release 114:1–14

    Google Scholar 

  14. Guang-Wei, Hui D, Xiang-Bing (2010) Preparation of ivermectin liposome and its pharmacokinetics and treatments in goats. Chin J Vet Parasitol 5:123–132

    Google Scholar 

  15. Hauff P, Reinhard M, Briel A, Debus N, Schirner M (2004) Molecular targeting of lymph nodes with L-selectin ligand-specific US contrast agent, A feasibility study in mice and dogs. Radiology 231:667–673

    PubMed  Article  Google Scholar 

  16. Kawashima Y (2006) Nanoparticulate systems for improved drug delivery. Adv Drug Del Rev 47:11–16

    Google Scholar 

  17. Kotze AF, Thanou MM, Luebetaen HL, de Boer AG (1999) Enhancement of paracellular drug transport with highly quaternized N-trimethyl chitosan chloride in neutral environments: in vitro evaluation in intestinal epithelial cells (Caco-2). J Pharm Sci 88:253–257

    PubMed  Article  CAS  Google Scholar 

  18. Kuang XX, Guang-Wei, Hui D, Xiang-Bing M, Yi L (2006) Study on the acute toxicity of ivermectin liposome. Chin J Vet Parasitol 4:67–72

    Google Scholar 

  19. Li T, Shi XW, Du YM, Tang YF (2007) Quaternized chitosan/alginate nanoparticles for protein delivery. J Biomed Mater Res A 83(2):383–390

    PubMed  Google Scholar 

  20. Lu B, Xiong SB, Yang H (2005) Mitoxantrone- loaded BSA nanospheres and chitosan nanospheres for local injection against breast cancer and its lymph node metastases II: tissue distribution and pharmacodynamics. Int J Pharm 5:561–57

    Google Scholar 

  21. Lu B, Xiong SB, Yang H (2006) Solid lipid nanoparticles of mitoxantrone for local injection against breast cancer and its lymph node metastases. Eur J Pharm Biopharm 56:86–95

    Google Scholar 

  22. Maincent P (1992) Lymphatic targeting of polymeric nanoparticles after intraperitoneal administration in rats. Pharm Res 9(12):1534–1539

    PubMed  Article  CAS  Google Scholar 

  23. Manish G, Vimukta S (2011) Targeted drug delivery system: a review. Res J Chem Sci 2:135–141

    Google Scholar 

  24. Marcato PD, Durán N (2008) New aspects of nanopharmaceutical delivery systems. J Nanosci Nanotechnol 8:1–14

    Article  Google Scholar 

  25. Misra S, Chaterjee RK, Sen AB (1984) The response of Litomosides carinii to antifilarial agents in cotton rats Sigmodon hispidus and multimammate rat. Indian J Med Res 79:749–752

    PubMed  CAS  Google Scholar 

  26. Mohanraj VJ, Chen Y (2006) Nanoparticles—a review. Trop J Pharm Res 5(1):561–567

    Google Scholar 

  27. Motwani SK, Chopra S, Talegaonkar S, Kohli K, Ahmad FJ, Khar RK (2007) Chitosan–sodium alginate nanoparticles as submicroscopic reservoirs for ocular delivery: formulation, optimization and in vitro characterization. Eur J Pharm Biopharm 68:513–525

    PubMed  Google Scholar 

  28. Moulia-Pelat JP, Glaziou P, Weil GJ, Nguyen LN, Gaxotte P, Nicolas L (1995) Combination ivermectin plus diethylcarbamazine, a new effective tool for control of lymphatic filariasis. Trop Med Parasitol 46(1):9–12

    PubMed  CAS  Google Scholar 

  29. Paily KP, Hoti SL, Das PK (2009) A review of the complexity of biology of lymphatic filarial parasites. J Parasit Dis 33(1–2):3–12

    PubMed  Article  CAS  Google Scholar 

  30. Petrak K (2006) Nanotechnology and site-targeted drug delivery. J Biomater Sci Polym Ed 17(11):1209–1219

    PubMed  Article  CAS  Google Scholar 

  31. Porter CJH (1997) Drug delivery to the lymphatic system. Crit Rev Ther Drug Carrier Syst 14:333–393

    PubMed  CAS  Google Scholar 

  32. Sankalia MG, Mashru RC, Sankalia JM, Sutariya VB (2007) Reversed chitosan–alginate polyelectrolyte complex for stability improvement of alpha-amylase: optimization and physicochemical characterization. Eur J Pharm Biopharm 65:215–232

    PubMed  Article  CAS  Google Scholar 

  33. Sartori C, Finch DS, Ralph B (1997) Determination of the cation content of alginate thin films by FTIR spectroscopy. Polymer 38:43–51

    Article  CAS  Google Scholar 

  34. Silva MS, Cocenza DS, Grillo R, Silva de Melo NR, Tonello PS, Oliveira LC, Cassimiro DL, Rosa AH, Fraceto LF (2011) Paraquat-loaded alginate/chitosan nanoparticles: preparation, characterization and soil sorption studies. J Hazard Mater 190:366–374

    Article  CAS  Google Scholar 

  35. Singh PK, Ajay A, Kushwaha S (2010) Towards novel antifilarial drugs: challenges and recent developments. Futur Med Chem 2(2):251–283

    Article  CAS  Google Scholar 

  36. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20

    PubMed  Article  CAS  Google Scholar 

  37. Teli MK, Mutalik S, Rajanikant GK (2010) Nanotechnology and nanomedicine: going small means aiming big. Curr Pharm Des 16(16):1882–1892

    PubMed  Article  CAS  Google Scholar 

  38. Wei L, Xia X (2008) Study on the effect of ivermectin liposome in treating swine sarcoptidosis. Chin J Vet Parasitol 3:44–50

    Google Scholar 

  39. World Health Organization (2010) WHO global programme to eliminate lymphatic filariasis progress report for 2000–2009 and strategic plan 2010–2020. World Health Organization, Geneva

    Google Scholar 

  40. Yong-xin, Wangdui B, Zhu SE, Shu-hai HE, Jing W, Lu-de D (2010) Determination of content and entrapment efficiency for ivermectin liposomes by HPLC. China Anim Husb Vet Med 4:190–196

    Google Scholar 

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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.

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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).

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