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.