Editors' ChoiceInfectious Disease

Nanoparticle gets the worm

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Science Translational Medicine  25 May 2016:
Vol. 8, Issue 340, pp. 340ec85
DOI: 10.1126/scitranslmed.aaf9199

Lymphatic filariasis, a mosquito-borne tropical disease, currently infects an estimated 120 million people, and another 1.2 billion people across 58 countries are at risk for infection. As a result of infection-associated complications, it is the second leading cause of permanent or long-term disability, with over 40 million sufferers worldwide. Existing antifilarial agents exhibit poor efficacy in treating the infections because the adult stage worms reside in lymphatic tissues, which necessitates prolonged treatment schedules with high doses of drugs leading to unwanted side effects and poor patient compliance. Singh et al. developed a formulation and delivery approach to overcome these limitations and dramatically improve drug efficacy in controlling filarial worm infections.

The authors made biomaterial nanoparticles that were loaded with doxycycline, a drug that reduces infections in humans but normally requires prolonged high doses, limiting its use in mass drug administration programs. By making the particles a size optimal for uptake into lymphatics, 100 nm in diameter or less, treatment with drug-loaded nanoparticles markedly increased drug concentrations within lymphatic tissues after subcutaneous injection compared with administration of free drug alone. Strikingly, the drug-loaded nanoparticles were able to eliminate Brugia malayi filarial worm infections in a Mastomys coucha rodent model with only five doses. Drug-loaded nanoparticles also increased the extent of female worm sterilization. In contrast, the free drug could achieve neither goal.

This study suggests that biomaterial-based formulation strategies can be used to create shorter, safer drug treatment regimens for the elimination of filarial infections. It also demonstrates the potential for the optimization of drug formulation for lymphatic delivery in improving drug bioactivity against filarial parasites that infect lymphatic tissues.

Y. Singh et al., Subcutaneously administered ultrafine PLGA nanoparticles containing doxycycline hydrochloride target lymphatic filarial parasites. Mol. Pharmaceutics 10.1021/acs.molpharmaceut.6b00206 (2016). [Abstract]

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