Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment

Fayyaz, Heba A.; EL-Massik, Magda A.; Bahey-El-Din, Mohammed; Abdel-Bary, Amany; Abdallah, Ossama Y.; Eltaher, Hoda M.

doi:10.1016/j.ijpharm.2023.123663

International Journal of Pharmaceutics

2024

DOI: 10.1016/j.ijpharm.2023.123663

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Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment

Heba A. Fayyaz,

Magda A. EL-Massik,

Mohammed Bahey-El-Din

et al.

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2024

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Cited by 2 publications

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Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma

El-Melegy,

El-Kamel,

Mehanna

et al. 2024

Drug Deliv. and Transl. Res.

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Despite its established anti-diabetic activity, Metformin hydrochloride (MET) has been repurposed for the management of hepatocellular carcinoma (HCC). Owing to MET high aqueous solubility and poor oral permeability, a novel nanoplatform is sought to overcome the current challenges of traditional formulations. In this study, we developed MET-bridged nanocochleates (MET-CO) using a direct bridging method followed by optimization and assessment using various in-vitro and in-vivo pharmacokinetic methods. The optimized nanocochleates MET-CODCP 19, containing dicetyl phosphate (DCP), displayed uniform snail-shaped nano-rolls measuring 136.41 ± 2.11 nm with a PDI of 0.241 ± 0.005 and a highly negative ζ-potential of -61.93 ± 2.57 mV. With an impressive MET encochleation efficiency (> 75%), MET-CODCP 19 exhibited a controlled biphasic release profile, with minimal initial burst followed by prolonged release for 24 h. Importantly, they showed significant MET permeation in both in-vitro Caco-2 and ex-vivo intestinal models compared to non-DCP containing formula or MET solution. The in-vivo oral bioavailability study demonstrated pronounced improvements in the pharmacokinetic parameters with a 5.5 relative bioavailability compared to MET solution. Notably, a significant reduction in IC50 values in HepG2 cells after 24 h of treatment was observed. Furthermore, the optimized formulation showed a significant downregulation of anti-apoptotic and cancer stemness genes, with 12- and 2-fold lower expression compared to MET solution. These promising results highlight the efficacy of the novel MET-bridged nanocochleates as a stable nanoplatform for enhancing the oral bioavailability of MET and boosting its anticancer potential against HCC. Graphical Abstract

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Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma

El-Melegy,

El-Kamel,

Mehanna

et al. 2024

Drug Deliv. and Transl. Res.

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New and emerging roles for inhalational and direct antifungal drug delivery approaches for treatment of invasive fungal infections

Neoh,

Jeong,

Kong

et al. 2024

Expert Review of Anti-infective Therapy

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Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment

Cited by 2 publications

References 72 publications

Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma

Stable self-assembled oral metformin-bridged nanocochleates against hepatocellular carcinoma

New and emerging roles for inhalational and direct antifungal drug delivery approaches for treatment of invasive fungal infections

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