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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 special nanoparticles that can cross the protective barrier surrounding the brain by using a protein from a fungal infection. These nanoparticles are loaded with an antifungal drug and can effectively treat cryptococcal brain infections in laboratory tests. This approach offers a new way to deliver medicines to the brain without invasive procedures, potentially helping patients with serious brain infections that are currently difficult to treat.

Background

Neural cryptococcosis is a fatal CNS infection caused by Cryptococcus neoformans that affects over 100,000 people annually. The blood-brain barrier (BBB) presents a major obstacle to delivering therapeutic drugs to the CNS. Cryptococcus neoformans secretes a metalloprotease (Mpr1) that facilitates its own BBB crossing, which could potentially be harnessed to deliver antifungal drugs.

Objective

To engineer Mpr1-functionalized PLGA nanoparticles loaded with amphotericin B and evaluate their ability to cross the BBB and treat neural cryptococcosis in vitro.

Results

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

Conclusion

Mpr1-coating of polymeric nanoparticles is a promising noninvasive strategy for enhancing drug delivery across the BBB to treat CNS infections. The approach successfully combines fungal-derived proteolytic activity with antifungal drug encapsulation to improve both BBB penetration and therapeutic efficacy.
  • Published in:PLoS ONE,
  • Study Type:In vitro experimental study,
  • Source: 10.1371/journal.pone.0340202, PMID: 41544065
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