101. Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis
- Author
-
José A. García-Salcedo, Teresa del Castillo, José L. Arias, José Maceira, José Hernández-Quero, Stefan Magez, Miguel Soriano, Juan D. Unciti-Broceta, and Cellular and Molecular Immunology
- Subjects
Drug ,media_common.quotation_subject ,Trypanosoma brucei brucei ,Pharmaceutical Science ,Trypanosoma brucei ,Epitopes ,chemistry.chemical_compound ,Polylactic Acid-Polyglycolic Acid Copolymer ,In vivo ,medicine ,Animals ,African trypanosomiasis ,Lactic Acid ,Pentamidine ,media_common ,Nanobody nanoparticles conjugation ,Drug Carriers ,biology ,Human African trypanosomiasis ,PEGylation ,PLGA ,Single-Domain Antibodies ,medicine.disease ,biology.organism_classification ,Trypanocidal Agents ,Virology ,Endocytosis ,specific cell targeting ,Mice, Inbred C57BL ,Trypanosomiasis, African ,polymeric nanoparticles ,chemistry ,Nanoparticles ,Female ,Nanocarriers ,Polyglycolic Acid ,medicine.drug - 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 pathogenTrypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug forT. b. gambienseacute infection. Anin vitroeffectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore,in vivotherapy 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.
- Published
- 2015