|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|
|Date Published||2015 Jan 10|
|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|
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.
|Alternate Journal||J Control Release|
Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.