Physicochemical properties of water and its effect on drug delivery

Loftsson, Þorsteinn; Brewster, Marcus E.

doi:10.1016/j.ijpharm.2007.08.049

Cited by 28 publications

(27 citation statements)

References 58 publications

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“…The large concentration of R-CD has an impact on water structure and thereby also on the solvation of the analyte ions. [34][35][36] It has, for example, been shown that approximately 35 water molecules are closely associated to R-CDs in solution 35 which inevitably will affect the solvation of ions. In fact, the presence of structure-creating solutes (also called kosmotropes) based on carbohydrates has previously been found to affect the permeation of analytes through lipid membranes.…”

Section: Resultsmentioning

confidence: 99%

Effect of α-Cyclodextrin on Drug Distribution Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

et al. 2009

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The description and understanding of noncovalent interactions and distribution of potential new drug compounds in an organism is of paramount importance for the successful development of new drugs. In this work, a new procedure based on electrochemistry at the interface between two immiscible electrolyte solutions (ITIES) for addressing and discriminating between drug compound/ligand interactions in aqueous solution and nonspecific ligand effects on oil-water distribution behavior has been developed. The procedure is demonstrated using five drug compounds with different physical chemical parameters and alpha-cyclodextrin as the aqueous phase ligand. Alpha-cyclodextrin was chosen as an aqueous phase ligand, as it is frequently used in drug formulations to enhance solubility and bioavailability of drug compounds. Supplementary capillary electrophoresis experiments provided more detailed information on alpha-cyclodextrin drug complexation and, in combination with the electrochemical studies, provided information on solvation effects affecting the oil-water distribution of the drug compounds. The use of ligand shift ion partition diagrams for data presentation is a convenient format for the visualization of ligand effects on distribution behavior of related drug compounds.

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Section: Resultsmentioning

confidence: 99%

Effect of α-Cyclodextrin on Drug Distribution Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

et al. 2009

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“…This is because the aqueous medium adjacent to the membrane surface is less mobile due to hydrogen bonds formed at the interface (Loftsson and Brewster, 2008). Hence, even vigorous stirring is unable to remove the ABL totally.…”

Section: Pcel-x Software For Correction Of Abl Designing Experimentsmentioning

confidence: 99%

“…The cellular permeability coefficient, P C , was introduced through studies at different stirring rates by Karlsson and Artursson (1991). ABL also depends on the interaction between the aqueous phase and membrane surface (Loftsson and Brewster, 2008) including a complex glycocalyx that differs between cell models. Hence, the interaction between the aqueous buffer and the cell membrane surface will be different from the interaction between the buffer and either coated or uncoated porous membrane surface.…”

Section: Other Approaches To Correct In Vitro Permeability Data For Amentioning

confidence: 99%

In vitro porcine blood–brain barrier model for permeability studies: pCEL-X software pKaFLUX method for aqueous boundary layer correction and detailed data analysis

Yusof

Avdeef²,

Abbott

2014

European Journal of Pharmaceutical Sciences

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In vitro blood-brain barrier (BBB) models from primary brain endothelial cells can closely resemble the in vivo BBB, offering valuable models to assay BBB functions and to screen potential central nervous system drugs. We have recently developed an in vitro BBB model using primary porcine brain endothelial cells. The model shows expression of tight junction proteins and high transendothelial electrical resistance, evidence for a restrictive paracellular pathway. Validation studies using small drug-like compounds demonstrated functional uptake and efflux transporters, showing the suitability of the model to assay drug permeability. However, one limitation of in vitro model permeability measurement is the presence of the aqueous boundary layer (ABL) resulting from inefficient stirring during the permeability assay. The ABL can be a rate-limiting step in permeation, particularly for lipophilic compounds, causing underestimation of the permeability. If the ABL effect is ignored, the permeability measured in vitro will not reflect the permeability in vivo. To address the issue, we explored the combination of in vitro permeability measurement using our porcine model with the pKa(FLUX) method in pCEL-X software to correct for the ABL effect and allow a detailed analysis of in vitro (transendothelial) permeability data, Papp. Published Papp using porcine models generated by our group and other groups are also analyzed. From the Papp, intrinsic transcellular permeability (P0) is derived by simultaneous refinement using a weighted nonlinear regression, taking into account permeability through the ABL, paracellular permeability and filter restrictions on permeation. The in vitro P0 derived for 22 compounds (35 measurements) showed good correlation with P0 derived from in situ brain perfusion data (r(2)=0.61). The analysis also gave evidence for carrier-mediated uptake of naloxone, propranolol and vinblastine. The combination of the in vitro porcine model and the software analysis provides a useful tool to better predict BBB permeability in vivo and gain better mechanistic information about BBB permeation.

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“…The crystalline structure of eupafolin was therefore changed to an amorphous state; 3) The presence of hydrogen bond interactions between pure compound and polymer is another index for evaluating the enhancement of aqueous solubility and bioavailability. 51 The results from 1 H NMR and FTIR analyses revealed that the aromatic ring of eupafolin formed an intermolecular hydrogen bond with Eudragit E100 and PVA. As a consequence of the above factors, ENDS showed a 67.6-fold particle size reduction, which increased its water solubility.…”

Section: Discussionmentioning

confidence: 99%

Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress

Lin

Lee²,

Tsai

et al. 2016

IJN

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Exposure to particulate matter (PM), a major form of air pollution, can induce oxidative stress and inflammation and may lead to many diseases in various organ systems including the skin. Eupafolin, a flavonoid compound derived from Phyla nodiflora , has been previously shown to exhibit various pharmacological activities, including antioxidant and anti-inflammatory effects. Unfortunately, eupafolin is characterized by poor water solubility and skin penetration, which limits its clinical applications. To address these issues, we successfully synthesized a eupafolin nanoparticle delivery system (ENDS). Our findings showed that ENDS could overcome the physicochemical drawbacks of raw eupafolin with respect to water solubility and skin penetration, through reduction of particle size and formation of an amorphous state with hydrogen bonding. Moreover, ENDS was superior to raw eupafolin in attenuating PM-induced oxidative stress and inflammation in HaCaT keratinocytes, by mediating the antioxidant pathway (decreased reactive oxygen species production and nicotinamide adenine dinucleotide phosphate oxidase activity) and anti-inflammation pathway (decreased cyclooxygenase-2 expression and prostaglandin E2 production through downregulation of mitogen-activated protein kinase and nuclear factor-κB signaling). In summary, ENDS shows better antioxidant and anti-inflammatory activities than raw eupafolin through improvement of water solubility and skin penetration. Therefore, ENDS may potentially be used as a medicinal drug and/or cosmeceutical product to prevent PM-induced skin inflammation.

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Physicochemical properties of water and its effect on drug delivery

Cited by 28 publications

References 58 publications

Effect of α-Cyclodextrin on Drug Distribution Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

Effect of α-Cyclodextrin on Drug Distribution Studied by Electrochemistry at Interfaces between Immiscible Electrolyte Solutions

In vitro porcine blood–brain barrier model for permeability studies: pCEL-X software pKaFLUX method for aqueous boundary layer correction and detailed data analysis

Eupafolin nanoparticles protect HaCaT keratinocytes from particulate matter-induced inflammation and oxidative stress

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