Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.

TitleNanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.
Publication TypeJournal Article
Year of Publication2015
AuthorsArias, J. L., J. D. Unciti-Broceta, J. Maceira, T. Del Castillo, J. Hernández-Quero, S. Magez, M. Soriano, and J. A. Garcia-Salcedo
JournalJ Control Release
Volume197
Pagination190-8
Date Published2015 Jan 10
ISSN1873-4995
KeywordsAnimals, Drug Carriers, Endocytosis, Epitopes, Female, Lactic Acid, Mice, Inbred C57BL, Nanoparticles, Pentamidine, Polyglycolic Acid, Single-Domain Antibodies, Trypanocidal Agents, Trypanosoma brucei brucei, Trypanosomiasis, African
Abstract

Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.

DOI10.1016/j.jconrel.2014.11.002
Alternate JournalJ Control Release
PubMed ID25445702
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