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Senicapoc (SEN), a potent antisickling agent, shows poor water solubility and poor oral bioavailability. To improve the solubility and cell permeation of SEN, self-nanoemulsifying drug delivery systems (SNEDDSs) were developed. Capryol PGMC®, which showed the highest solubilization capacity, was selected as the oil. The self-emulsification ability of two surfactants, viz., Cremophor-EL® and Tween® 80, was compared. Based on a solubility study and ternary phase diagrams, three optimized nanoemulsions with droplet sizes less than 200 nm were prepared. An in vitro dissolution study demonstrated the superior performance of the SNEDDS over the free drug. During in vitro lipolysis, 80% of SEN loaded in the SNEDDS remained solubilized. An in vitro cytotoxicity study using the Caco-2 cell line indicated the safety of the formulations at 1 mg/mL. The transport of SEN-SNEDDSs across Caco-2 monolayers was enhanced 115-fold (p < 0.01) compared to that of the free drug. According to these results, SNEDDS formulations could be promising tools for the oral delivery of SEN., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

β-Arteether, an effective artemisinin derivative, is used in the treatment of malaria but available only as an intramuscular injection. The objective of this work was to develop lipid-based formulations for oral administration of β-arteether. Self-emulsifying drug delivery systems (SEDDSs) of low cost and with accessible excipients (groundnut or sesame oil, Maisine 35-1, Tween 80 or Cremophor EL, and absolute ethanol) were formulated. In 250 ml of simulated gastric medium, 1g of these SEDDS solubilized the daily dose of β-arteether and formed lipid droplets of average size 80-250 nm. No toxicity against Caco-2 intestinal cells was observed. Using a mouse model, the efficacy of these arteether lipid formulations against Plasmodium berghei was evaluated. A daily dose of 24 mg/kg for 4 days led to complete cure for more than 45 days in 100% of treated mice and had an antimalarial efficacy comparable to that of an intramuscular oily solution of arteether and significantly higher than that of an oily solution of β-arteether given orally at the same dose. In conclusion, lipid-based drug delivery systems constitute a promising approach for the oral administration of β-arteether., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Diabetes is a metabolic pathology with chronic high blood glucose levels that occurs when the pancreas does not produce enough insulin or the body does not properly use the insulin it produces. Diabetes management is a puzzle and focuses on a healthy lifestyle, physical exercise, and medication. Thus far, the condition remains incurable; management just helps to control it. Its medical treatment is expensive and is to be followed for the long term, which is why people, especially from low-income countries, resort to herbal medicines. However, many active compounds isolated from plants (phytocompounds) are poorly bioavailable due to their low solubility, low permeability, or rapid elimination. To overcome these impediments and to alleviate the cost burden on disadvantaged populations, plant nanomedicines are being studied. Nanoparticulate formulations containing antidiabetic plant extracts or phytocompounds have shown promising results. We herein aimed to provide an overview of the use of lipid- and inorganic-based nanoparticulate delivery systems with plant extracts or phytocompounds for the treatment of diabetes while highlighting their advantages and limitations for clinical application. The findings from the reviewed works showed that these nanoparticulate formulations resulted in high antidiabetic activity at low doses compared to the corresponding plant extracts or phytocompounds alone. Moreover, it was shown that nanoparticulate systems address the poor bioavailability of herbal medicines, but the lack of enough preclinical and clinical pharmacokinetic and/or pharmacodynamic trials still delays their use in diabetic patients. [ABSTRACT FROM AUTHOR]

Selective drug delivery to inflamed tissues is of widespread interest for the treatment of inflammatory bowel disease (IBD). Because a lack of physiological lipids has been described in patients suffering IBD, and some lipids present immunomodulatory properties, we hypothesize that the combination of lipids and anti-inflammatory drugs together within a nanocarrier may be a valuable strategy for overcoming IBD. In the present study, we investigated and compared the in vitro and in vivo efficacy of three lipid-based nanocarriers containing curcumin (CC) as an anti-inflammatory drug for treating IBD in a murine DSS-induced colitis model. These nanocarriers included self-nanoemulsifying drug delivery systems (SNEDDS), nanostructured lipid carriers (NLC) and lipid core-shell protamine nanocapsules (NC). In vitro , a 30-fold higher CC permeability across Caco-2 cell monolayers was obtained using NC compared to SNEDDS (NC > SNEDDS > NLC and CC suspension). The CC SNEDDS and CC NLC but not the CC NC or CC suspension significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo , only CC NLC were able to significantly decrease neutrophil infiltration and TNF-α secretion and, thus, colonic inflammation. Our results show that a higher CC permeability does not correlate with a higher efficacy in IBD treatment, which suggests that lipidic nanocarriers exhibiting increased CC retention at the intestinal site, rather than increased CC permeability are efficient treatments of IBD. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin (CC), a potential antimalarial drug, has poor water solubility, stability and oral bioavailability. To circumvent these pitfalls, lipid-based drug delivery systems (LBDDSs) with a high CC loading (30mg/g) were formulated. In a biorelevant gastric medium, CC-LBDDSs formed particle sizes in the range of 30–40nm. During in vitro lipolysis, 90–95% of the CC remained solubilized, whereas 5–10% of the CC precipitated as an amorphous solid, with a high rate of re-dissolution in a biorelevant intestinal medium. The transport of the CC-LBDDS across Caco-2 monolayers was enhanced compared with the transport of free drug because of the increased CC solubility. In Plasmodium berghei-infected mice, modest antimalarial efficacy was observed following oral treatment with CC-LBDDSs. However, the combination therapy of CC-LBDDS with a subtherapeutic dose of β-arteether-LBDDS provided an increase in protection and survival rate that was associated with a significant delay in recrudescence. These findings suggest that the combination of oral CC and β-arteether lipid-based formulations may constitute a promising approach for the treatment of malaria. [Copyright &y& Elsevier]

Low aqueous solubility and poor oral bioavailability are limiting factors in the oral delivery of voxelotor, an antisickling agent. To overcome these limitations, a voxelotor self-nanoemulsifying drug delivery system was developed. Various oils, surfactants, and cosurfactants were screened for their solubilization potential for the drug. The area of nanoemulsification was identified using a ternary phase diagram. An experimental mixture design and a desirability function were applied to select SNEDDSs that contain a maximum amount of lipids and a minimum amount of surfactant, and that possess optimal emulsification properties (i.e., droplet sizes, polydispersity index (PDI), emulsification time, and transmittance percentage). The optimized SNEDDS formulation was evaluated for the self-emulsifying time (32 s), droplet size (35 nm), and zeta potential (−8 mV). In vitro dissolution studies indicated a 3.1-fold improvement in drug solubility from the optimized SNEDDS over pure drug powder. After 60 min of in vitro lipolysis, 88% of the voxelotor loaded in the SNEDDS remained in the aqueous phase. Cytotoxicity evaluation, using Caco-2 cells, indicated the safety of the formulation at 0.9 mg/mL. The transport of the voxelotor SNEDDS across Caco-2 monolayers was significantly enhanced compared to that of the free drug. Compared to the drug suspension, the developed SNEDDS enhanced the oral bioavailability (1.7-fold) of voxelotor in rats. The results suggest that further development of SNEDDSs for the oral delivery of voxelotor is needed. [ABSTRACT FROM AUTHOR]

Nano-scaled particles have been found to preferentially accumulate in inflamed regions. Local delivery of anti-inflammatory drugs loaded in nanoparticles to the inflamed colonic site is of great interest for inflammatory bowel disease (IBD) treatment. Curcumin (CC) is an anti-inflammatory local agent, which presents poor ADME properties. Hence, we evaluated, both in vitro and in vivo , the local delivery of CC using pH-sensitive polymeric nanoparticles (NPs) combining both poly(lactide- c o-glycolide) acid (PLGA) and a polymethacrylate polymer (Eudragit ® S100). CC-NPs significantly enhanced CC permeation across Caco-2 cell monolayers when compared to CC in suspension. CC-NPs significantly reduced TNF-α secretion by LPS-activated macrophages (J774 cells). In vivo , CC-NPs significantly decreased neutrophil infiltration and TNF-α secretion while maintaining the colonic structure similar to the control group in a murine DSS-induced colitis model. Our results support the use of nanoparticles made of PLGA and Eudragit ® S100 combination for CC delivery in IBD treatment. [ABSTRACT FROM AUTHOR]