Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance
Abstract
:1. Introduction
2. Overview of AmpB Nanoformulations
3. Factors Affecting Bioavailability of Orally Administered AmpB Nanoformulations
3.1. Impact of Nanoencapsulation of AmpB on Oral Bioavailability of AmpB
3.2. Effect of Encapsulation Efficiency on Oral Bioavailability
3.3. Effect of Surface Modification of Nanoparticles on Oral Bioavailability
3.4. Effect of Stability of AmpB Offered by Nanoparticle in Gastrointestinal Fluids on Oral Bioavailability
4. Clinical Trials Involving Oral AmpB Nanoformulations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Drug Delivery System | Method of Preparation, Major Components and Key Features | Outcome | Ref. |
---|---|---|---|
Nanoparticles Nanosuspensions | Nanoprecipitation: PLGA, poloxamer 188 and 388. Size: 86–153 nm; ZP −31.0 mV. Solvent-antisolvent precipitation: PVA, DMSO. Size: 118–400 nm; ZP −20 mV. | AMP-B-loaded NP showed 2-fold and AmpB nanosuspensions showed 4-fold enhancement in antifungal activity compared to AmBisome® in a mouse model. | [35] |
Mannose anchored thiomer nanocarriers | Covalent linkage of thioglycolic-chitosan followed by mannose addition: Mannose, chitosan. Size: 430–482 nm | 6-fold increase in oral BA and 3-fold increase in half-life with significantly less toxicity than the AmpB control. | [36] |
Liposomes | Modified injection method: Egg yolk phosphatidylcholine, cholesterol, ceramides. Size: 200 nm, EE > 75% | In an in vitro stomach–duodenum model, ceramides offered better membrane stability to ceramics anchored liposomes. Moreover, ceramides inhibited the detergent effect of bile salts on liposome membranes. | [37] |
Cubosomes | High-pressure homogenization: Glyceryl monoolein, poloxamer 407. Size: 192 nm, EE > 94% | AmpB-loaded glyceryl monoolein cubosomes showed enhanced therapeutic efficacy than Fungizone®. A two-day treatment of 10 mg/kg dose was sufficient to attain therapeutic concentrations at the renal tissues for fungal treatment. | [38] |
Solid lipid nanoparticles (SLN) | Nanoprecipitation followed by probe sonication: Glyceride dilaurate, phosphatidylcholine, PEG-660–12 hydroxystearate. Size: 200 nm, EE > 95% | In vivo pharmacokinetics evaluation on Wistar rats showed faster onset of action and prolonged half-life than pure drug solution. | [30] |
Nanostructured lipid carriers (NLC) | Homogenization ultrasonication: Chitosan, beeswax, coconut oil. Size: 394 nm, EE > 86% | NLC formulation showed comparable antifungal (in vitro) efficacy than AmpB and is twice less toxic to RBCs. | [39] |
Stealth nanoparticles | Emulsification diffusion: PLGA-PEG copolymers, PVA, vitamin E, pluronic F68. Size: <1000 nm, EE > 56% | PEG concentration plays a significant role in size, EE, and drug release. 15% PEG demonstrated a controlled drug release of 54% up to 24 h. | [40] |
Nanocapsules | Nanoemulsion production by emulsion solvent evaporation followed by chitosan deposition. Mannose sugar, chitosan, soya lecithin, polysorbate 80. Size:198 nm; ZP +31 mV, EE 96%. | Increased macrophage selectivity by interacting with overexpressed mannose receptors, resulting in 90% reduction in spleen parasite load and decreased nephrotoxicity. | [41] |
Lipopolymerosome | Single-step nanoprecipitation: Glycol–chitosan, stearic acid, soya lecithin, cholesterol. Size: 243 nm; ZP +27 mV. | In vitro and in vivo evaluation demonstrated improved plasma drug stability and reduced toxicity compared to AmBisome® and Fungizone®. Enhanced anti-leishmanial activities and the glycol–chitosan copolymer was vital in improving the drug stability. | [42] |
Polymer–lipid hybrid nanoparticles (PLN) | Desolvation method: Gelatin, lecithin, acetone, DMSO. Size: 253 nm, EE > 50.0% | Drug release followed Huguchi kinetics. Moreover, a 6-fold increase in intestinal permeability on Caco-2 cell lines and a 5-fold enhancement in oral BA was found compared to free AmpB. | [34] |
Nanocochleates | Film hydration: Phosphatidylserine, lecithin, cholesterol, vitamin E. ZP −9 to −16 mV, EE > 50.0%. | Enhanced gastric stability and slow release in the GI medium. A confocal microscopy study demonstrated the integration of phosphatidylserine to the Caco-2 intestinal cell layers and slow drug release. | [43] |
Self-emulsifying drug delivery systems (SEDDS) | Solvent evaporation: Glyceryl mono-oleate, PEG, phospholipids. Size: 200–400 nm, enhanced solubility stability in SGF or SIF | SEDDS significantly decreased fungal CFU in Sprague–Dawley rats infected with A. fumigatus and Candida albicans without causing renal toxicities. | [44] |
Polymeric micelles | Solvent-diffusion and microfluidics technique: Copolymer Soluplus® (Polyvinyl caprolactam–PVA–PEG), VitE-TPGS Size: 80 nm, EE 95.0% | Enhanced cell uptake (6-fold) and permeability (2-fold) in Caco-2 cells in vitro while being less toxic than free AmpB. | [45] |
Nanofibers | Electrospinning technique. PLGA, chloroform, 2,2,2-trifluoroethanol. Size: 582 nm, controlled delivery of AmpB for 8 days. | For vulvovaginal candidiasis, the vaginal fungal load in a murine model was eliminated after three days of local treatment. | [46] |
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Fairuz, S.; Nair, R.S.; Billa, N. Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance. Pharmaceutics 2022, 14, 1823. https://doi.org/10.3390/pharmaceutics14091823
Fairuz S, Nair RS, Billa N. Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance. Pharmaceutics. 2022; 14(9):1823. https://doi.org/10.3390/pharmaceutics14091823
Chicago/Turabian StyleFairuz, Shadreen, Rajesh Sreedharan Nair, and Nashiru Billa. 2022. "Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance" Pharmaceutics 14, no. 9: 1823. https://doi.org/10.3390/pharmaceutics14091823
APA StyleFairuz, S., Nair, R. S., & Billa, N. (2022). Orally Administered Amphotericin B Nanoformulations: Physical Properties of Nanoparticle Carriers on Bioavailability and Clinical Relevance. Pharmaceutics, 14(9), 1823. https://doi.org/10.3390/pharmaceutics14091823