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Nanoparticles as drug carriers for malaria

A study by researchers from the Institute for Bioengineering of Catalonia () and the (CRESIB) demonstrates that an encapsulated in nanoparticles – chloroquine salts in polyamidoamine polymers – is significantly more effective when delivered in vivo than free (unencapsulated) drugs and may help to curb drug resistance.

The study, which is published in the , indicates that the nanoparticles are capable of recognising different Plasmodium species, making their potential as carriers for malarial drugs broader than that of other options.

Current malaria therapies require strategies capable of selectively delivering drugs to the cells infected by Plasmodium. In this study, the researchers explored the usefulness of two polymeric nanosystems, AGMA1 and ISA23, as carriers for drugs that selectively target the pathogen. The first, AGMA1, also has activity, which is demonstrated by its inhibition of the growth of Plasmodium falciparum in vitro.

The study showed that both polymers bind preferentially to Plasmodium-infected red blood cells, compared to uninfected cells. Moreover, they are capable of recognising widely divergent species, such as P. falciparum and P. yoelii, malaria parasites that infect humans and mice respectively. Administration of 0.8 mg/kg of the drug chloroquine as either AGMA1 or ISA23 salts cured P yoelii-infected mice, whereas control animals treated with twice as much free drug did not survive.

“These polymers which can encapsulate have low toxicity, high biodegradability and selectively target red blood cells infected by different species of Plasmodium,” explains Xavier Fernàndez-Busquets, head of the Nanomalaria joint unit of IBEC/CRESIB, who led the study. “This all means that they’re extremely promising candidates as therapeutic antimalarials.”

This exciting potential has been boosted by recent funding for the Nanomalaria joint unit from the Fondazione Cariplo to develop these polymeric prototypes, with the aim of engineering an antimalarial nanovector that’s ready to enter the preclinical pipeline. While reducing the evolution of drug resistance, a nanovector engineered to carry the lower doses required in this type of targeted delivery could also make it a cheaper and more viable option for Africa.

Source

Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium, Patricia Urbána, Juan José Valle-Delgado, Nicolò Mauro, Joana Marques, Amedea Manfredi, Matthias Rottmann, Elisabetta Ranucci, Paolo Ferruti, Xavier Fernàndez-Busquets, Journal of Controlled Release, DOI: 10.1016/j.jconrel.2013.12.032, March 2014

Institute for Bioengineering of Catalonia (IBEC)