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Nanotechnology: meeting the future of Veterinary Parasitology Research

Abstract:

The field of nanotechnology involves an array of different areas of expertize with the application of innovative products in Medicine, Engineering, and to a less extent to Veterinary Medicine. In our opinion, more research is needed, in special to Animal Parasitology, to develop state of the art products to solve old problems. Livestock, pets and wildlife may benefit from products in nanoscale, such as vaccines, target recombinant proteins, or new drug candidates. Thus, we want to give some food for thought to drive scientific programs into nanotechnology, creating a safer environment to animals and humans

Index Terms:
Biotechnology; parasite control; vaccines; RNAi

NANOTECHNOLOGY literally means any technology performed on a nanoscale that has practical applications to our everyday activities. This encompasses the production and usage of physical, chemical, or biological systems at scales ranging from individual atoms or molecules to submicron dimensions, as well as the integration of the resulting nanostructures into larger systems ( HYPERLINK "#mkp_ref_02" Bhushan B. 2010. Introduction to Nanotechnology, Springer Handbook of Nanotechnology. 3rd ed. Springer, Heidelberg, Germany. 15p.).

The Fantastic Voyage (1966) was the first movie that illustrated the use of nanotechnology in medicine to the large public. In it, the scientist Jan Benes was saved from a blood clot by an expedition using the submarine Proteus, miniaturized to the scale of 1000 nm. For this impressive screenplay, the film won the Oscar for best special effects. The brilliant creativity of the writer of the film, Harry Kleiner, was only the beginning of the nanomedicine breakthrough of the following three decades.

More recently, the funding for nanotechnology research was in the order of US$67 billions, running at US$10 billion/year (Cientifica 2013Cientifica 2013. Global Funding of Nanotechnologies. 2011 Edition. <http://www.cientifica.com/ research/market-reports/nanotech- funding-2011>
http://www.cientifica.com/ research/mark...
), mainly in the USA, Germany, China and Japan. By 2013, the USA multi-agency National Nanotechnology Initiative, has dedicated nearly US$1.8 billion to nanotechnology, where US$408 millions was related to life sciences (Nano 2013Nano2013. Budget brief for 2013. National Nanotechnology Initiative. Online Dec. 9, 2013 < 9, 2013 http://www.nano.gov/node/750 >
http://www.nano.gov/node/750...
). The European Union countries have a new financial instrument called Horizon 2020, which came to replace the successful Seventh Framework Program initiative by the end of 2013. Running from 2014 to 2020, the proposed EU$80 billion research money aims to harness innovation to drive new growth and jobs in the region (European Commission 2013European Commission 2013. Breakdown of the "Horizon 2020" budget.http://ec.europa.eu/research/horizon2020> Access on Dec. 9, 2013.
http://ec.europa.eu/research/horizon2020...
). Since 2011, China's nanotech funding has already surpassed the USA centering the resources into drug delivery and medical diagnostic research (Cientifica 2013Cientifica 2013. Global Funding of Nanotechnologies. 2011 Edition. <http://www.cientifica.com/ research/market-reports/nanotech- funding-2011>
http://www.cientifica.com/ research/mark...
).

Nanotechnology has given the tools to medicine to improve treatments and to develop effective immune responses against infectious agents. Cancer research has been the major area met by nanotechnology. Diseases caused by bacteria, fungi and viruses have also been targets for nanoparticles. Nanotech can offer an improvement in imaging and diagnosis of the diseases as well, slipping away the limitations of biological barriers. Despite the advances of the nanomedicine, the technology is still a long way from perfection due to the difficulties to get the milestone of clinical trials, where only a few nanoproducts have arrived to the clinical phase ( HYPERLINK "#mkp_ref_03" Bourzac K. 2012. Nanotechnology: carrying drugs. Nature 491:S58-60.).

The French Veterinary Academy held the first conference on nanotechnology in veterinary medicine this year in Jouy-en-Josas, presenting ground breaking research on the subject, identifying promising areas to pursue and discuss the foreseeable impact on veterinary pharmacology and diagnostic capabilities.Even with the fact of the advancement of nanotech to human health, parasitic diseases have only a few applications and the reports related to nano-parasitology focus mostly on Leishmania sp. and Plasmodium sp. ( HYPERLINK "#mkp_ref_04" Carvalho R.F., Ribeiro I.F., Miranda-Vilela A.L., Souza Filho J., Martins O.P. & Silva D.O. 2013. Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice. Exp. Parasitol.135:217-222., HYPERLINK "#mkp_ref_12" Waknine-Grinberg J.H., Even-Chen S., Avichzer J., Turjeman K., Bentura-Marciano A. & Haynes R. 2013. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria. PLoS ONE 8:2722). But they have demonstrated the potentialities of nanotech applications into research and development

The development of a new drug delivery system favoring longer dose intervals and the increase of drug activity against parasites are some of the major issues studied in nano-parasitology. Active and non-active targeting has been explored using liposomes, solid lipid nanoparticles and hydrophobic polymeric nanoparticles ( HYPERLINK "#mkp_ref_11" Santos-Magalhães N.S. & Mosqueira V.C.S. 2010. Nanotechnology applied to the treatment of malaria. Adv. Drug Del. Rev. 62:560-575.). Nanoparticles carriers have also improved the bioavailability and drug selectivity, even in very complicated treatments like cerebral malaria by Plasmodium falciparum infection ( HYPERLINK "#mkp_ref_12" Waknine-Grinberg J.H., Even-Chen S., Avichzer J., Turjeman K., Bentura-Marciano A. & Haynes R. 2013. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria. PLoS ONE 8:2722).

One of the most important problems in parasitology research as well as, to the Veterinary counterpart is the development of drug resistance ( HYPERLINK "#mkp_ref_08" Molento M.B. 2009. Parasite control in the age of drug resistance. Vet. Parasitol. 3:188-196.). Nanoparticles may offer a potent tool to reduce the risk of resistance to traditional drugs, avoiding some of the resistance mechanisms, increasing drug bioavailability and potentiating the target of the treatment. New antiparasitic drugs can also be developed with nanotechnology like the case of Tio2@Ag nanoparticles ( HYPERLINK "#mkp_ref_01" Allahverdiyev A.M., Abamor E.S., Bagirova M., Baydar S., Ates S. & Kaya F. 2013. Investigation of antileishmanial activities of Tio2@Ag nanoparticles on biological properties of L. tropica and L. infantum parasites in vitro. Exp. Parasitol. 135:55-63.), being an eco-friendly and inexpensive approach for use in veterinary medicine.

Pegylated or polyplex nanoparticles offer fantastic options to increase the biodistribution of a compound. Nanoparticles can help veterinary medicine in mass treatments of ectoparasites, facilitating the drug-parasite interaction. The effectiveness of phytotherapeutic products can be improved, like the recent treatment of antiparasitic silver nanoparticles using Cissus quadrangularis against Hippobosca aculata and Rhipicephalus (Boophilus) microplus ( HYPERLINK "#mkp_ref_10" Santhoshkumar T., Rahuman A.A., Bagavan A., Marimuthu S., Jayaseelan C. & Kirthi A.V. 2012. Evaluation of stem aqueous extract and synthesized silver nanoparticles using Cissus quadrangularis against Hippobosca maculata and Rhipicephalus (Boophilus) microplus. Exp. Parasitol.132:156-165.). It could also allow the potential recombinant proteins to act at different drug binding sites, as nanovectors ( HYPERLINK "#mkp_ref_05" Devalapally H., Chakilam A. & Amiji M.M. 2007. Role of nanotechnology in pharmaceutical product development. J. Pharm. Sci. 96:2547-2565.). The active gold coated glass particles commonly known as nanoshells could help veterinary medicine to improve the treatment of parasites facilitating the target of the parasite and the drug delivery, physically destroying the infection. Also nanoshells can be useful in the study of host-parasite as biosensors. Nanodevices can allow the diagnostic of parasite in herds allowing veterinarians to suggest a correct health management. We would like to let you know that our research groups in Cuba and Brazil are currently running preliminary test using nanopeptides against ruminant helminths (Haemonchus contortus and Fasciola hepatica).

Nanotechnology can also allow the development of adjuvants for veterinary parasite vaccines, boosting their present low efficacy. Vaccines using nanoparticles as adjuvants have the further potential to induce both antibody and cellular immune response by simultaneously activating the major histocompatibility complex class I and class II pathways or increase the antigen visibility and their lifespan, to meet the host immune system. Recently, a nano-microparticulated malaria vaccine elicited long-lasting protective antibody titers with only a single dose ( HYPERLINK "#mkp_ref_06" Dinglasan R.R., Armistead J.S., Nyland J.F., Jiang X. & Mao HQ. 2013. Single-dose microparticle delivery of a malaria transmission-blocking vaccine elicits a long-lasting functional antibody response. Curr. Mol. Med. 13:479-487.). Although it is necessary that quantum chemistry overcome their limitations, new nanodevices could allow a better comprehension of the host-parasite interaction. It can also help to facilitate the studies of parasites life cycle and their geographical distribution. Thus, nanoparticles are a strong tool to elucidate the parasite gene function in the era of omics.

Concluding Remarks

Despite the potentialities of the use of nanotechnology in veterinary parasitology research we think that only a few successful applications have been accomplished so far. A small number of parasites have been the target for nanotechnology, focusing primarily in Leishmania sp. and Plasmodium sp. research. Although various benefits were demonstrated, a more active research is necessary to apply this technology to the real needs of animal health, taking into account the economic constraints of this sector. Nanotechnology as any other technology is getting good exposure in Brazil, but researchers must also take into account the ethical and regulatory issues (scientific monitoring, risk assessment, target species, aberrant results and safety to other organisms) before its widespread use.

References

  • Allahverdiyev A.M., Abamor E.S., Bagirova M., Baydar S., Ates S. & Kaya F. 2013. Investigation of antileishmanial activities of Tio2@Ag nanoparticles on biological properties of L. tropica and L. infantum parasites in vitro Exp. Parasitol. 135:55-63.
  • Bhushan B. 2010. Introduction to Nanotechnology, Springer Handbook of Nanotechnology. 3rd ed. Springer, Heidelberg, Germany. 15p.
  • Bourzac K. 2012. Nanotechnology: carrying drugs. Nature 491:S58-60.
  • Carvalho R.F., Ribeiro I.F., Miranda-Vilela A.L., Souza Filho J., Martins O.P. & Silva D.O. 2013. Leishmanicidal activity of amphotericin B encapsulated in PLGA-DMSA nanoparticles to treat cutaneous leishmaniasis in C57BL/6 mice. Exp. Parasitol.135:217-222.
  • Cientifica 2013. Global Funding of Nanotechnologies. 2011 Edition. <http://www.cientifica.com/ research/market-reports/nanotech- funding-2011>
    » http://www.cientifica.com/ research/market-reports/nanotech- funding-2011
  • Devalapally H., Chakilam A. & Amiji M.M. 2007. Role of nanotechnology in pharmaceutical product development. J. Pharm. Sci. 96:2547-2565.
  • Dinglasan R.R., Armistead J.S., Nyland J.F., Jiang X. & Mao HQ. 2013. Single-dose microparticle delivery of a malaria transmission-blocking vaccine elicits a long-lasting functional antibody response. Curr. Mol. Med. 13:479-487.
  • European Commission 2013. Breakdown of the "Horizon 2020" budget.http://ec.europa.eu/research/horizon2020> Access on Dec. 9, 2013.
    » http://ec.europa.eu/research/horizon2020
  • Molento M.B. 2009. Parasite control in the age of drug resistance. Vet. Parasitol. 3:188-196.
  • Nano2013. Budget brief for 2013. National Nanotechnology Initiative. Online Dec. 9, 2013 < 9, 2013 http://www.nano.gov/node/750 >
    » http://www.nano.gov/node/750
  • Santhoshkumar T., Rahuman A.A., Bagavan A., Marimuthu S., Jayaseelan C. & Kirthi A.V. 2012. Evaluation of stem aqueous extract and synthesized silver nanoparticles using Cissus quadrangularis against Hippobosca maculata and Rhipicephalus (Boophilus) microplus Exp. Parasitol.132:156-165.
  • Santos-Magalhães N.S. & Mosqueira V.C.S. 2010. Nanotechnology applied to the treatment of malaria. Adv. Drug Del. Rev. 62:560-575.
  • Waknine-Grinberg J.H., Even-Chen S., Avichzer J., Turjeman K., Bentura-Marciano A. & Haynes R. 2013. Glucocorticosteroids in nano-sterically stabilized liposomes are efficacious for elimination of the acute symptoms of experimental cerebral malaria. PLoS ONE 8:2722

Publication Dates

  • Publication in this collection
    Oct 2015

History

  • Received
    30 Apr 2015
  • Accepted
    07 Aug 2015
Colégio Brasileiro de Patologia Animal - CBPA Pesquisa Veterinária Brasileira, Caixa Postal 74.591, 23890-000 Rio de Janeiro, RJ, Brasil, Tel./Fax: (55 21) 2682-1081 - Rio de Janeiro - RJ - Brazil
E-mail: pvb@pvb.com.br