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Lyophilized Iron Oxide Nanoparticles Encapsulated in Amphotericin B: A Novel Targeted Nano Drug Delivery System for the Treatment of Systemic Fungal Infections

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Plough Center for Sterile Drug Delivery Systems, University of Tennessee Health Science Center, Memphis, TN 38163, USA
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Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(3), 247; https://doi.org/10.3390/pharmaceutics12030247
Received: 29 January 2020 / Revised: 1 March 2020 / Accepted: 3 March 2020 / Published: 10 March 2020
We formulated and tested a targeted nanodrug delivery system to help treat life-threatening invasive fungal infections, such as cryptococcal meningitis. Various designs of iron oxide nanoparticles (IONP) (34–40 nm) coated with bovine serum albumin and coated and targeted with amphotericin B (AMB-IONP), were formulated by applying a layer-by-layer approach. The nanoparticles were monodispersed and spherical in shape, and the lead formulation was found to be in an optimum range for nanomedicine with size (≤36 nm), zeta potential (−20 mV), and poly dispersity index (≤0.2), and the drug loading was 13.6 ± 6.9 µg of AMB/mg of IONP. The drug release profile indicated a burst release of up to 3 h, followed by a sustained drug release of up to 72 h. The lead showed a time-dependent cellular uptake in C. albicans and C. glabrata clinical isolates, and exhibited an improved efficacy (16–25-fold) over a marketed conventional AMB-deoxycholate product in susceptibility testing. Intracellular trafficking of AMB-IONP by TEM and confocal laser scanning microscopy confirmed the successful delivery of the AMB payload at and/or inside the fungal cells leading to potential therapeutic advantages over the AMB-deoxycholate product. A short-term stability study at 5 °C and 25 °C for up to two months showed that the lyophilized form was stable. View Full-Text
Keywords: nanoparticle(s); theranostics; targeted drug delivery; antiinfective(s); lyophilization; albumin; drug delivery system(s); drug transport; colloid(s); coating nanoparticle(s); theranostics; targeted drug delivery; antiinfective(s); lyophilization; albumin; drug delivery system(s); drug transport; colloid(s); coating
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Balabathula, P.; Whaley, S.G.; Janagam, D.R.; Mittal, N.K.; Mandal, B.; Thoma, L.A.; Rogers, P.D.; Wood, G.C. Lyophilized Iron Oxide Nanoparticles Encapsulated in Amphotericin B: A Novel Targeted Nano Drug Delivery System for the Treatment of Systemic Fungal Infections. Pharmaceutics 2020, 12, 247.

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