Strategies to enhance oral delivery of amphotericin B: a comparison of uncoated and enteric-coated nanostructured lipid carriers

Abstract

The oral delivery of amphotericin B (AmB) has remained a challenge due to its low solubility, permeability, and instability in gastric acidic pH. To solve these issues, herein, we reported a novel approach of using nanostructured lipid carriers (NLCs) and NLCs coating with Eudragit V R L100-55 (Eu-NLCs) for the oral delivery of AmB. This study aimed to compare their ability in protecting the drug from degradation in gastrointestinal fluids and permeation enhancement in Caco-2 cells. Uncoated NLCs and Eu-NLCs possessed a mean particle size of $180 and $550 nm, with a zeta potential of $À30 and $À50 mV, respectively. Both NLCs demonstrated an AmB entrapment efficiency up to $75%. They possessed significantly greater AmB water solubility than the free drug by up to 10-fold. In fasted state simulated gastric fluid, Eu-NLCs provided significantly greater AmB protection from acidic degradation than uncoated NLCs. In fasted state simulated intestinal fluid, both uncoated and Eu-NLCs showed a fast release characteristic. Caco-2 cells permeation studies revealed that uncoated NLCs provided significantly higher apparent permeation coefficient (P app) value than Eu-NLCs. Moreover, after 6 months of storage at 4 C in the absence of light, the physicochemical stabilities of the lyophilized uncoated and Eu-NLCs could be maintained. In conclusion, the developed NLCs and Eu-NLCs could be a potential drug delivery system in improving the oral bioavailability of AmB.

Solid Dispersion Incorporated into Dissolving Microneedles for Improved Antifungal Activity of Amphotericin B: In Vivo Study in a Fungal Keratitis Model

“…Overall, all SD formulations were able to improve the solubility of AMB, where SD1 showed the highest modulation, up to a > 8-fold increase in solubility compared to the pure AMB as the control. This result was in line with several previous research that used SD-AMB and nanostructured lipid carriers of AMB for solubility enhancement, demonstrating a significant increase in solubility compared to pure AMB. , …”

“…This result was in line with several previous research that used SD-AMB and nanostructured lipid carriers of AMB for solubility enhancement, demonstrating a significant increase in solubility compared to pure AMB. 17,44 The results of the SD-AMB formula that had the highest solubility was found in SD1, which had a mixture of AMB:PVP (5:5) with a solubility of 1.71 ± 0.01 μg/mL; then, the next highest solubility was found in SD6, which had a mixture of AMB:PEG (5:5) with a solubility of 1.32 ± 0.01 μg/mL. Meanwhile, the solubility of pure AMB was 0.2 ± 0.01 μg/mL, which was significantly different (p < 0.05) compared to the SD-AMB formula.…”

Potential lipid-based strategies of amphotericin B designed for oral administration in clinical application

“…Nanostructured lipid carriers (NLCs) attract more attention due to their ability to promote intestinal absorption and enhance oral bioavailability of AmB (Senna et al., 2018 ; Ghosh et al., 2019 ). Pataranapa et al developed a novel NLCs coating with Eudragit® L100-55 (Eu-NLCs) for improving drug stability in gastrointestinal fluids (Nimtrakul et al., 2020 ). Enteric pH-dependent Eudragit L100-55® as pharmaceutical excipients have been widely applied for enteric-coated tablet as it is soluble in medium of pH > 5.5 (Moustafine et al., 2008 ).…”

“…Eu-NLCs possessed a particle size of 550 nm with entrapment efficiency up to 75%, and significantly enhanced AmB water solubility by up to 10-fold compared with the free drug. In fasted state simulated gastric fluid, Eu-NLCs provided a better ability to protect the drug from degradation in gastric fluid (Nimtrakul et al., 2020 ). However, the work only was performed in vitro, but not in animal or human (Nimtrakul et al., 2020 ).…”

“…In fasted state simulated gastric fluid, Eu-NLCs provided a better ability to protect the drug from degradation in gastric fluid (Nimtrakul et al., 2020 ). However, the work only was performed in vitro, but not in animal or human (Nimtrakul et al., 2020 ). Shabi et al.…”