Therapeutic Efficacy of Carvacrol-Loaded Mesoporous Silicate Nanoparticles Against Cryptosporidiosis.

Purpose: Cryptosporidiosis is a parasitic inflammatory disease that causes the death of around 1.6 million people annually worldwide and is associated with Cryptosporidium parvum (C. parvum) infection. This study aimed to evaluate the therapeutic efficacy of carvacrol (CV) loaded into mesoporous silicate nanoparticles (MSNs) against C. parvum using in vitro, in vivo, histopathological, immunohistochemical, biochemical, and computational approaches. Methods: In vitro assays were conducted to evaluate the oocysticidal activity of CV-loaded MSNs (CV-MSNs) for 96 h. In silico assays were carried out to investigate target inflammatory proteins involved in cryptosporidiosis. In vivo tests were performed on male Swiss albino mice (22 ± 5 g, 4-6 weeks) to assess the anti-inflammatory and antioxidant effects of CV after loading onto MSNs. Results: CV showed its highest oocysticidal efficacy after loading onto spherical 72 nm MSNs (MSN2), exhibiting a 0.07 mg/mL LC50. At the in vivo level, CV-MSN2 markedly restored ileal, pulmonary, and hepatic histoarchitecture and normalized biochemical indices in infected mice. CV-MSN2 also showed the strongest inhibitory action against computationally selected target proteins, TLR-4, NF-κb-P65, STAT-3, NOS2, and JAK-1, with accompanying downregulation of IL-6, IL-1β, and TNF-α. Similarly, antioxidant markers were significantly decreased following CV-MSN2 treatment compared to the positive controls. Conclusions: This study shows that MSNs enhanced CV efficacy against ileal inflammation induced by C. parvum, preserving CV's molecular targets.