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

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®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 ∼−30 and ∼−50 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 (Papp) 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

Assessing clinical evidence of drug interactions between citrus juices and cyclosporine

Background: Previous studies have demonstrated that grapefruit juice increased the bioavailability of cyclosporine;however, the results from the literature are inconsistent. Other citrus fruits such as pomelo or orange juice had variable effects on the bioavailability of cyclosporine.Objective: To assess the effect of grapefruit juice and other types of citrus juice on oral bioavailability of cyclosporine in humans using meta-Analysis.Methods: We conducted a meta-Analysis of placebo-controlled studies evaluating the effects of citrus juices on bioavailability of cyclosporine. The studies were identified in PubMed, Cochrane CENTRAL, CINAHL, ISI Web of Knowledge, Psych Info International, Pharmaceutical Abstract (IPA), and reference lists of relevant papers. The weighted-mean difference (WMD) was calculated for net changes in the area under the curve (AUC) of cyclosporine. All studies conducted as placebo-controlled crossover studies in humans to compare the effect of citrus juices and control (drinking water) on AUC of cyclosporine and/or Cmin,ss were reviewed. All studies included were evaluated and extracted independently, and discrepancies were resolved through discussion.Results: Eighteen studies were identified. A subgroup analysis suggested that grapefruit juice significantly increased AUC of cyclosporine (WMD = 1762.5 ng·h/ml, 95%CI = 1178.9-2346.0 ng·h/ml, p > 0.001). While a meta-Analysis of all other types of citrus juices (tangerine juice, Seville orange juice, sweet orange juice, and citrus soda) except pomelo juice revealed no effect on the AUC of cyclosporine (WMD = -181.0 ng·h/ml,95%CI = -582.8-220.9 ng·h/ml, p > 0.5), a study of pomelo juice indicated a significant increase in the AUC of cyclosporine.Conclusions: Grapefruit juice intake increases oral bioavailability of cyclosporine in both healthy volunteers and renal transplant patients, whereas all other types of citrus juices may not have an influence on the oral bioavailability of cyclosporine. Current evidence suggests that pomelo juice may be able to increase cyclosporine oral bioavailability