19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water

Omran, Ahmed A.; Kitamura, Kazuya; Takegami, Shigehiko; Kume, Manabu; Yoshida, Megumi; El‐Sayed, Amr; Mohamed, Marghny H.; Abdel-Mottaleb, Mohamed

doi:10.1016/s0731-7085(02)00438-7

Cited by 12 publications

(5 citation statements)

References 12 publications

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“…Nevertheless, liposomes became excellence model systems to mimic membranes, due to their amphiphilic character (absent in octanol/water systems), anisotropic nature (versus the isotropic nature of octanol) and structural similarity with biological membranes [ 67 , 68 ]. Generally, the partition constants are determined by spectroscopic techniques as nuclear magnetic resonance (NMR) [ 69 , 70 , 71 ], derivative spectrophotometry [ 71 , 72 , 73 , 74 ], and fluorescence spectroscopy [ 74 , 75 , 76 , 77 ], the last one being the most sensitive [ 78 ]. Additionally,

values determined by computational approaches have been recently reported [ 38 , 79 , 80 , 81 ].…”

Section: Metalloantibiotic-membrane Interactionsmentioning

confidence: 99%

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Ferreira

Gameiro

2021

Microorganisms

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Fluoroquinolones (FQs) are antibiotics widely used in the clinical practice due to their large spectrum of action against Gram‑negative and some Gram-positive bacteria. Nevertheless, the misuse and overuse of these antibiotics has triggered the development of bacterial resistance mechanisms. One of the strategies to circumvent this problem is the complexation of FQs with transition metal ions, known as metalloantibiotics, which can promote different activity and enhanced pharmacological behaviour. Here, we discuss the stability of FQ metalloantibiotics and their possible translocation pathways. The main goal of the present review is to frame the present knowledge on the conjunction of biophysical and biological tools that can help to unravel the antibacterial action of FQ metalloantibiotics. An additional goal is to shed light on the studies that must be accomplished to ensure stability and viability of such metalloantibiotics. Potentiometric, spectroscopic, microscopic, microbiological, and computational techniques are surveyed. Stability and partition constants, interaction with membrane porins and elucidation of their role in the influx, determination of the antimicrobial activity against multidrug‑resistant (MDR) clinical isolates, elucidation of the mechanism of action, and toxicity assays are described for FQ metalloantibiotics.

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values determined by computational approaches have been recently reported [ 38 , 79 , 80 , 81 ].…”

Section: Metalloantibiotic-membrane Interactionsmentioning

confidence: 99%

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Ferreira

Gameiro

2021

Microorganisms

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“…The initial volume of the TFP solution was kept relatively low (500 mL) so as to shift the partition equilibrium of the drug toward the membrane when the lipid was added. The partition coefficient (log P PC ) for TFP in phosphatidylcholine LMVs was estimated to be 3.88 by following an adaptation of the 19 F NMR method described by Omran et al 14 in which the 19 F T 1 relaxation times for TFP were measured at different lipid concentrations to yield a binding curve. 15 From this value, the fraction F of the total drug concentration within the DMPC membranes can be calculated from…”

Section: Sample Preparationmentioning

confidence: 99%

The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR

Boland

Middleton

2008

Phys. Chem. Chem. Phys.

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Methods for determining how a drug interacts with cellular membranes at the molecular level can give valuable insight into the mode of action of the drug and its absorption, distribution and metabolism profile. A procedure is described here to determine the orientation and location of the lipophilic drug trifluoperazine (TFP) intercalated into dimyristoylphosphatidylcholine (DMPC) bilayers, by using a novel combination of high-resolution solid-state nuclear magnetic resonance (SSNMR) methods to observe signals from (13)C within the drug at natural abundance. SSNMR measurements of (1)H-(13)C dipolar couplings for TFP and selective broadening of (13)C NMR peaks by paramagnetic Mn(2+) together suggest a model for the location, orientation and dynamics of the drug within lipid bilayers that offers an explanation for the lysoprotective effect of the drug at low concentrations. The experiments described are straightforward to implement and can be used for the routine analysis of drug-membrane interactions to provide useful information for drug design and structure refinement.

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“…19 F nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for investigating the interaction between compounds containing 19 F atoms and biomolecules, because the 19 F nucleus is not present in natural biological substances and is thus easily detectable without interfering signals (17)(18)(19)(20)(21)(22)(23)(24). In addition, we have previously reported that the partition coefficients (K p s) of some fluorinated psychotropic drugs between PC small unilamellar vesicles and water can be successfully determined without disturbing the equilibrium condition by using the 19 F NMR method (25). As shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

19F Nuclear Magnetic Resonance Spectrometric Determination of the Partition Coefficients of Flutamide and Nilutamide (Antiprostate Cancer Drugs) in a Lipid Nano-Emulsion and Prediction of Its Encapsulation Efficiency for the Drugs

et al. 2016

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Abstract. To design a useful lipid drug carrier having a high encapsulation efficiency (EE%) for the antiprostate cancer drugs flutamide (FT) and nilutamide (NT), a lipid nano-emulsion (LNE) was prepared with soybean oil (SO), phosphatidylcholine (PC), and sodium palmitate, and the partition coefficients (K p s) of the drugs for the LNE were determined by 19 F nuclear magnetic resonance (NMR) spectrometry. The 19 F NMR signal of the trifluoromethyl group of both drugs showed a downfield shift from an internal standard (trifluoroethanol) and broadening according to the increase in the lipid concentration due to their interaction with LNE particles. The difference in the chemical shift (Δδ) of each drug caused by the addition of LNE was measured under different amounts of LNE, and the K p values were calculated from the Δδ values. The results showed that FT has higher lipophilicity than NT. The total lipid concentration (SO + PC) required to encapsulate each drug into LNE with an EE% of more than 95% was calculated from the K p values as 93.3 and 189.9 mmol/L for FT and NT, respectively. For an LNE prepared with the total lipid concentration of 215 mmol/L, the predicted EE% values were 98 and 96% for FT and NT, respectively, while the experimental EE% values determined by a centrifugation method were approximately 99% for both drugs. Thus, the 19 F NMR spectrometric method is a useful technique to obtain the K p values of fluorinated drugs and thereby predict the theoretical lipid concentrations and prepare LNEs with high EE% values.

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19F NMR spectrometric determination of the partition coefficients of some fluorinated psychotropic drugs between phosphatidylcholine bilayer vesicles and water

Cited by 12 publications

References 12 publications

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance

The dynamics and orientation of a lipophilic drug within model membranes determined by 13C solid-state NMR

19F Nuclear Magnetic Resonance Spectrometric Determination of the Partition Coefficients of Flutamide and Nilutamide (Antiprostate Cancer Drugs) in a Lipid Nano-Emulsion and Prediction of Its Encapsulation Efficiency for the Drugs

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