Title | Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Arias, J. L., J. D. Unciti-Broceta, J. Maceira, T. Del Castillo, J. Hernández-Quero, S. Magez, M. Soriano, and J. A. Garcia-Salcedo |
Journal | J Control Release |
Volume | 197 |
Pagination | 190-8 |
Date Published | 2015 Jan 10 |
ISSN | 1873-4995 |
Keywords | Animals, 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. |
DOI | 10.1016/j.jconrel.2014.11.002 |
Alternate Journal | J Control Release |
PubMed ID | 25445702 |
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