Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis
Open accessAbstract
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.
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Nanoparticle-based treatment with pentamidine encapsulated in PLGA nanoparticles functionalized with a nanobody enabled a tenfold dose reduction in vivo.
“Nanoparticle-based treatment enabled a tenfold dose reduction in vivo.”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [55]
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Nanotechnology approaches for global infectious diseases
Kirtane, A. R., Verma, M., Karandikar, P., Furin, J., Langer, R., & Traverso, G. (2021) · Nature Nanotechnology · doi:10.1038/s41565-021-00866-8 · Cited by 520 · see citing works
- Authors
- Arias, J. L., Unciti-Broceta, J. D., Maceira, J., del Castillo, T., Hernández-Quero, J., Magez, S., Soriano, M., & García-Salcedo, J. A.
- Affiliations
- Universidad de Granada (ES)
- Vrije Universiteit Brussel (BE)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 197
- Pages
- 190-198
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2067109503
- Cited by
- 88
- References
- 65
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 5 · 2019: 15 · 2018: 8 · 2017: 8 · 2016: 6 · 2015: 5
- FWCI
- 2.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Plan Nacional de Investigación (SAF2011-30528)
- European Union (FP7-HEALTH-2007-B-2.3.4-1.223048)
- Instituto de Salud Carlos III, Spain (FIS 11/02571)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- sleeping sickness, Trypanosoma brucei, nanobodies, PLGA nanoparticles, PEGylated nanoparticles, targeted drug delivery, variant surface glycoprotein, pentamidine, Trypanosoma brucei gambiense, drug nanocarriers, active targeting, antiparasitic treatment
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Epitopes, Drug Carriers, Endocytosis, Female, Mice, Inbred C57BL, Pentamidine, Polyglycolic Acid, Trypanocidal Agents, Trypanosoma brucei brucei, Trypanosomiasis, African, Lactic Acid, Nanoparticles, Single-Domain Antibodies
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