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Conjugation of a Cryptococcus neoformans-derived metalloprotease to antifungal-loaded PLGA nanoparticles treats neural cryptococcosis in an in vitro model

Summary

Researchers developed tiny nanoparticle carriers coated with a fungal enzyme that helps them cross the protective barrier around the brain. These particles were loaded with an antifungal drug to treat brain infections caused by Cryptococcus neoformans. In laboratory tests, the Mpr1-coated particles successfully penetrated the blood-brain barrier better than regular nanoparticles and were more effective at killing the fungal cells.

Background

The blood-brain barrier (BBB) prevents most therapeutics from reaching the central nervous system, posing a significant challenge in treating CNS infections. Cryptococcus neoformans, a neurotropic fungal pathogen, utilizes a metalloprotease enzyme (Mpr1) to cross the BBB, which may be repurposed for drug delivery applications.

Objective

To engineer PLGA nanoparticles functionalized with the fungal metalloprotease Mpr1 and loaded with amphotericin B to enhance drug delivery across the blood-brain barrier and treat neural cryptococcosis in an in vitro model.

Results

Mpr1-functionalized nanoparticles demonstrated increased penetration across the in vitro BBB model compared to non-functionalized nanoparticles. When loaded with amphotericin B, Mpr1-conjugated nanoparticles reduced fungal burden two-fold and achieved an 8-fold lower minimum inhibitory concentration compared to free amphotericin B against both fungal species.

Conclusion

Mpr1-coating of polymeric nanoparticles represents a promising non-invasive strategy to enhance therapeutic delivery to the brain, with potential applications for treating CNS-disseminated cryptococcosis and other central nervous system infections.
  • Published in:PLoS One,
  • Study Type:In vitro Experimental Study,
  • Source: PMID: 41544065, doi: 10.1371/journal.pone.0340202
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