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Therapeutic efficacy of poly (lactic-co-glycolic acid) nanoparticles encapsulated ivermectin (nano-ivermectin) against brugian filariasis in experimental rodent model

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Abstract

The present study reports on the antifilarial activity of poly (lactic-co-glycolic acid) nanoparticles encapsulated ivermectin (nano-IVM) against human lymphatic filariid Brugia malayi in rodent host Mastomys coucha. Nano-IVM was prepared and optimized by nanoprecipitation method. The selected nano-IVM (F5) showed a uniform spherical shape with 96 nm diameter and 74.12 % entrapment efficiency, and when used at a suboptimal dose of 100 μg/kg body weight, completely eliminated filarial parasites from systemic circulation on 60 days post-infection in animals inflicted with B. malayi. In contrast, the coadministration of nano-IVM (F5) along with standard filaricide diethylcarbamazine (DEC) was found to be competent enough to suppress microfilarial stage of parasites and successfully eliminated microfilaria at 45 days posttreatment. However, the free form of both the drugs alone or in combination was unable to impart such suppression and followed by recurrence of the infection. Interestingly, nano-IVM (F5) was also found to be effective against adult stage parasites causing 36.67 % worm mortality and 75.89 % in combination with DEC; however, female sterilization remain almost similar. Thus, the combination of entrapped IVM with DEC exhibited enhanced microfilaricidal and marginally better macrofilaricidal efficacy than any of the single formulation or drugs combination.

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References

  • Albanese A, Tang PS, Chan WCW (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–16

    Article  CAS  PubMed  Google Scholar 

  • Ash LR, Riley JM (1970) Development of sub periodic B. malayi in the jird (Meriones unguiculatus) with notes on infection in other rodents. J Parasitol 56:969–972

    Article  CAS  PubMed  Google Scholar 

  • Ali M, Alam S, Ahmad S, Dinda AK, Ahmad FJ (2011) Determination of ivermectin stability by high-performance thin-layer chromatography. International J of Drug Development & Research 3:240–247

    CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Ali M, Afzal M, Kaushik U, Bhattacharya SM, Ahmad FJ, Dinda AK (2013b) Perceptive solutions to anti-filarial chemotherapy of lymphatic filariasis from the plethora of nanomedical sciences. J Drug Target. doi:10.3109/1061186X.2013.832766

    Google Scholar 

  • Ali M, Afzal M, Verma M, Bhattacharya SM, Ahmad FJ, Dinda AK (2013c) Improved antifilarial activity of ivermectin in chitosan–alginate nanoparticles against human lymphatic filarial parasite, Brugia malayi. Parasitol Res 112(8):2933–2943

    Article  PubMed  Google Scholar 

  • Anitha K, Shenoy RK (2001) Treatment of lymphatic filariasis: current trends, continuing medical education. Indian J Dermatol Venereol Leprol 67(2):60–65

    CAS  PubMed  Google Scholar 

  • Bajpai P, Vedi S, Owais M, Bhattacharya SM (2005) Use of liposomized tetracycline inelimination of Wolbachia endobacterium of human lymphatic filariid Brugia malayi in a rodent model. J Drug Target 13:375–381

    Article  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  • Bassi P, Kaur G (2010) pH modulation: a mechanism to obtain pH-independent drug release. Expert Opin Drug Deliv 7:845–57

    Article  CAS  PubMed  Google Scholar 

  • Bikram M, West JL (2008) Thermo-responsive systems for controlled drug delivery. Expert Opin Drug Deliv 5:1077–1091

    Article  CAS  PubMed  Google Scholar 

  • Bawa P, Pillay V, Choonara YE (2009) Stimuli-responsive polymers and their applications in drug delivery. Biomed Mater 4:234–245

    Article  Google Scholar 

  • Bhatt AD, Pethe AM (2010) Nanotechnology: a promising drug delivery for poorly water soluble drugs. Journal of Pharmacy Research 3:817–848

    Google Scholar 

  • Campbell WC (1983) Ivermectin: a potent new antiparasitic agent. Science 221:823–828

    Article  CAS  PubMed  Google Scholar 

  • Chrastina A, Massey KA, Schnitzer JE (2011) Overcoming in vivo barriers to targeted nanodelivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol 3(4):421–437

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Danhier F, Lecouturier N, Vromana B, Jérôme C, Marchand-Brynaert J, Ferond O, Préat V (2009) Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J of Controlled Release 133:11–17

    Article  CAS  Google Scholar 

  • Date AA, Joshi MD, Patravale VB (2007) Parasitic diseases: liposomes and polymeric nanoparticles versus lipid nanoparticles. Adv Drug Deliv Rev 10:505–521

    Article  Google Scholar 

  • Fox LM (2006) Ivermectin: uses and impact 20 years on. Curr Opin Infect Dis 19(6):588–593

    Article  PubMed  Google Scholar 

  • Fonseca C, Simoes S, Gaspar RE (2002) Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Controlled Release 83(2):273–286

    Article  CAS  Google Scholar 

  • Danhier F, Ansorena E, Silva JM, Coco R, Breton A, Préat V (2012) PLGA-based nanoparticles: an overview of biomedical applications. J Control Release 161:505–522

    Article  CAS  PubMed  Google Scholar 

  • Geary TG (2005) Ivermectin 20 years on: maturation of a wonder drug. TRENDS in Parasitology 21(11):45–55

    Article  Google Scholar 

  • Goa KL, McTavish D, Clissold SP (1991) Ivermectin. A review of its antifilarial activity, pharmacokinetic properties and clinical efficacy in onchocerciasis. Drugs 42(4):640–658

    Article  CAS  PubMed  Google Scholar 

  • Haldar KM, Haldar B, Chandra G (2013) Fabrication, characterization and mosquito larvicidal bioassay of silver nanoparticles synthesized from aqueous fruit extract of putranjiva, Drypetes roxburghii (Wall.). Parasitol Res 112(4):1451–1459

    Article  PubMed  Google Scholar 

  • Jayaseelan C, Rahuman AA, Rajakumar G, Kumar ST, Kirthi AV, Marimuthu S, Bagavan A, Kamaraj C, Zahir AA, Elango G (2012) Efficacy of plant-mediated synthesized silver nanoparticles against hematophagous parasites. Parasitol Res 111(2):921–933

    Article  PubMed  Google Scholar 

  • Kumar VK, Govindarajan M, Rajeswary M (2013a) Green synthesis of silver nanoparticles using Sida acuta (Malvaceae) leaf extract against Culex quinquefasciatus, Anopheles stephensi, and Aedes aegypti (Diptera: Culicidae). Parasitol Res 112(12):4073–4085

    Article  Google Scholar 

  • Kumar AN, Jeyalalitha T, Murugan K, Madhiyazhagan P (2013b) Bioefficacy of plant-mediated gold nanoparticles and Anthocepholus cadambaon filarial vector, Culex quinquefasciatus (Insecta: Diptera: Culicidae). Parasitol Res 112(3):1053–1063

    Article  PubMed  Google Scholar 

  • Kirthi AV, Rahuman AA, Rajakumar G, Marimuthu S, Kumar ST, Jayaseelan C, Velayutham K (2012) Acaricidal, pediculocidal and larvicidal activity of synthesized ZnO nanoparticles using wet chemical route against blood feeding parasites. Parasitol Res 109(2):461–472

    Article  Google Scholar 

  • Khanna VG, Kannabiran K, Rajakumar G, Rahuman AA, Kumar TS (2011) Biolarvicidal compound gymnemagenol isolated from leaf extract of miracle fruit plant, Gymnema sylvestre (Retz) Schult against malaria and filariasis vectors. Parasitol Res 109(5):1373–1386

    Article  PubMed  Google Scholar 

  • Kayser O, Kiderlen A, Croft S (2003) Natural products as antiparasitic drugs. Parasitol Res 90:55–62

    Article  Google Scholar 

  • Uhrich KE (1999) Polymeric systems for controlled drug release. Chem Rev 99:3181–3198

    Article  CAS  PubMed  Google Scholar 

  • Lakshmi V, Srivastava S, Mishra SS (2009) In vitro and in vivo antifilarial potential of marine sponge, Haliclona exigua (Kirkpatrick) against human lymphatic filarial parasite Brugia malayi. Parasitol Res 105(5):1295–1301

    Article  PubMed  Google Scholar 

  • Misra N, Sharma M, Raj K (2007) Chemical constituents and antifilarial activity of Lantana camara against human lymphatic filariid Brugia malayi and rodent filariid Acanthocheilonema viteae maintained in rodent hosts. Parasitol Res 100:439–448

    Article  PubMed  Google Scholar 

  • Martin RJ, Kusel JR, Robertson SJ, Minta A, Haugland RP (1992) Distribution of a fluorescent ivermectin probe, bodipy ivermectin, in tissues of the nematode parasite Ascaris suum. Parasitol Res 78(4):341–348

    Article  CAS  PubMed  Google Scholar 

  • Mu L, Feng SS (2003) A novel controlled release formulation for the anticancer drug Paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. J Control Release 86:33–48

    Article  CAS  PubMed  Google Scholar 

  • Merisko-Liversidge EM, Liversidge GG (2008) Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol Pathol 36:43–48

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  • 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 

  • Muthu MS, Singh S (2009) Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders. Nanomedicine 4(1):105–118

    Article  CAS  PubMed  Google Scholar 

  • Mahmud A, Xiong X, Montazeri H (2007) Polymeric micelles for drug targeting. J Drug Target 15:553–584

    Article  CAS  PubMed  Google Scholar 

  • 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 of Med Res 79:749–752

    CAS  Google Scholar 

  • Nayak A, Gayen P, Saini P (2012) Molecular evidence of curcumin induced apoptosis in the filarial worm Setaria cervi. Parasitol Res 111:1173–1186

    Article  PubMed  Google Scholar 

  • Oyibo W, Fagbenro-Beyioku A (1997) Community response to repeated annual ivermectin treatment of onchocerciasis in Nigeria. Parasitol Res 88(7):704–707

    Google Scholar 

  • Owais M, Misra-bhattacharya S, Haq W, Gupta CM (2003) Immunomodulator tuftsin augments antifilarial activity of diethylcarbamazine against experimental brugian filariasis. J Drug Target 11:247–251

    Article  CAS  PubMed  Google Scholar 

  • Piessens WF, Beldekas M (1979) Diethylcarbamazine enhances antibody mediated cellular adherence to Brugia malayi microfilariae. Nature 282:845–847

    Article  CAS  PubMed  Google Scholar 

  • Pourmand A, Pourmand MR, Wang J et al (2012) Application of nanomedicine in emergency medicine; point-of-care testing and drug delivery in twenty-first century. DARU J of Pharm Sci 20(1):20–26

    Article  Google Scholar 

  • Priscyla D, Marcato DN (2008) New aspects of nanopharmaceutical delivery systems. J Nanosci Nanotechnol 8:1–14

    Article  Google Scholar 

  • Romero EL, Morill MJ (2008) Drug delivery systems against leishmaniasis? Still an open question. Expert Opin Drug Deliv 5(7):805–882

    Article  CAS  PubMed  Google Scholar 

  • Rao UR, Chandrashekar R, Subrahmanyam D (1990) Effect of ivermectin on filariae of Mastomys natalensis. Parasitol Res 76(6):521–525

    Article  CAS  PubMed  Google Scholar 

  • Ros-Moreno RM, Moreno-Guzmán MJ, Jiménez-González A, Rodríguez-Caabeiro F (1999) Interaction of ivermectin with γ-aminobutyric acid receptors in Trichinella spiralis muscle larvae. Parasitol Res 85(4):320–323

    Article  CAS  PubMed  Google Scholar 

  • Subarani S, Sabhanayakam S, Kamaraj C (2013) Studies on the impact of biosynthesized silver nanoparticles (AgNPs) in relation to malaria and filariasis vector control against Anopheles stephensi Liston and Culex quinquefasciatus Say (Diptera: Culicidae). Parasitol Res 112(2):487–499

    Article  PubMed  Google Scholar 

  • Soni N, Prakash S (2012a) Efficacy of fungus mediated silver and gold nanoparticles against Aedes aegypti larvae. Parasitol Res 110(1):175–184

    Article  PubMed  Google Scholar 

  • Soni N, Prakash S (2012b) Fungal-mediated nano silver: an effective adulticide against mosquito. Parasitol Res 111(5):2091–2098

    Article  PubMed  Google Scholar 

  • Said DE, Samad LM, Gohar YM (2012) Validity of silver, chitosan, and curcumin nanoparticles as anti-Giardia agents. Parasitol Res 111(2):545–554

    Article  CAS  PubMed  Google Scholar 

  • Soll MD, Carmichael HI (1998) Efficacy of injectable ivermectin against the itch mit (Psorergates ovis) of sheep. Parasitol Res 75(1):81–82

    Article  Google Scholar 

  • Singh U, Misra S, Murthy PK, Katiyar JC, Agarwal A, Sircar AR (1997) Immunoreactive molecules of Brugia malayi and their diagnostic potential. Immunother Infect Dis 8:207–212

    Article  Google Scholar 

  • Santos-Magalhães NS, Mosqueira VC (2010) Nanotechnology applied to the treatment of malaria. Adv Drug Deliv Rev 62:560–575

    Article  PubMed  Google Scholar 

  • Sahni JK, Baboota S, Ali J (2011) Promising role of nanopharmaceuticals in drug delivery. Pharma Times 10:34–45

    Google Scholar 

  • Takakura Y (1996) Development of drug delivery systems for macromolecular drugs. Article in Japanese 116(7):519–532

    CAS  Google Scholar 

  • 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 

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Acknowledgments

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

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Correspondence to Mohammad Ali.

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Ali, M., Afzal, M., Verma, M. et al. Therapeutic efficacy of poly (lactic-co-glycolic acid) nanoparticles encapsulated ivermectin (nano-ivermectin) against brugian filariasis in experimental rodent model. Parasitol Res 113, 681–691 (2014). https://doi.org/10.1007/s00436-013-3696-5

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