期刊
JOURNAL OF CONTROLLED RELEASE
卷 197, 期 -, 页码 190-198出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2014.11.002
关键词
Polymeric nanoparticles; PLGA; Nanobody nanoparticles conjugation; PEGylation; Specific cell targeting; Human African trypanosomiasis
资金
- Plan Nacional de Investigacion (Ministerio de Economia y Competitividad, Spain) [SAF2011-30528]
- European Union [FP7-HEALTH-2007-B-2.3.4-1.223048]
- Instituto de Salud Carlos III, Spain [FIS 11/02571]
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. (C) 2014 Elsevier B.V. All rights reserved.
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