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Lipid Solubility (lipid + solubility)

Distribution by Scientific Domains

Chemistry	40%

Selected Abstracts

Lipid solubility- and concentration-dependent attenuation of in vitro natural killer cell cytotoxicity by local anesthetics

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2002
J. Krog
Background: Natural killer (NK) cells constitute an essential component of the innate immune system in the defence against infected and malignant cells. In this study the in vitro effect on NK cell activity of three different local anesthetics with different lipid solubility was investigated. Methods: Venous blood from seven healthy volunteers was incubated with three amide local anesthetics with three different concentrations of lipid solubility: lidocaine 0.50, 1.00 and 2.00 mg/ml, ropivacaine 0.375, 0.75 and 1.50 mg/ml, and bupivacaine 0.25, 0.50 and 1.00 mg/ml. After 1 h of incubation, mononuclear cells were isolated and cryopreserved until tested for NK cell cytotoxicity in a 4-h 51Cr-release assay against K-562 target cells. Natural killer cell cytotoxicity of mononuclear cells incubated with isotonic saline was used as the control. Results: A significant suppression in NK cell cytotoxicity was demonstrated for all three local anesthetic agents when the NK cell cytotoxicity was compared with the cytotoxicity estimated after incubation with the isotonic saline (P<0.004). Moreover a significant lipid solubility-dependent effect (P=0.0001) as well as an overall concentration-dependent effect (P<0.0001) on the NK cell cytotoxicity was found. Conclusion: The results of the present in vitro study suggest a negative association between the estimated NK cell cytotoxicity and the lipid solubility as well as the concentrations of the three local anesthetic agents tested. [source]

Designing for topical delivery: Prodrugs can make the difference

MEDICINAL RESEARCH REVIEWS, Issue 6 2003
Kenneth B. Sloan
Abstract It has been shown for homologous series of prodrugs that those members who were the more water soluble ones gave the greatest enhancement in topical delivery of the parent drug and not the more lipophilic ones. However, until recently models for topical delivery and equations to predict topical delivery focused only on lipid solubility (SLIPID) or partition coefficient (KOCT:AQ) and molecular volume (or molecular weight, MW) as parameters. Now several equations (transformed Potts,Guy or Series/Parallel) have been developed which include aqueous solubility (SAQ) as a parameter for predicting flux through skin. Experimental fluxes, solubilities, and MW from seven series of prodrugs have been fit to the transformed Potts,Guy equation to give coefficients for log solubility in isopropyl myristate (log SIPM) and log solubility in water (log SAQ) (0.53 and 0.47, respectively) which show, for parent drugs delivered by prodrugs from IPM in vitro through hairless mouse skin, that water solubility is almost as important as lipid solubility. When the transformed Potts,Guy equation was fit to data for the delivery of NSAID from mineral oil (MO) in vivo through human skin, the coefficients were 0.72 log SMO and 0.28 log SAQ. When the transformed Potts,Guy equation was fit to data for the delivery of their parent drugs by three series of prodrugs from water in vitro through hairless mouse skin the coefficients were 0.66 log SIPM and 0.34 log SAQ. Numerous recent examples are also given where more water-soluble members of homologous series of prodrugs give higher flux values from water vehicles in vitro through human skin than the more lipid soluble ones. © 2003 Wiley Periodicals, Inc. Med Res Rev, 23 No. 6, 763,793, 2003 [source]

Use of Physicochemical Property Limits to Develop Rules for Identifying Chemical Substances with no Skin Irritation or Corrosion Potential

MOLECULAR INFORMATICS, Issue 9 2004
Ingrid Gerner
Abstract This is believed to be the first paper to promote the use of rules based on (quantitative) structure-activity relationship [(Q)SAR] models for identifying chemicals that are not likely to cause a specific adverse health effect, viz., skin irritation or corrosion. The purpose of this paper is to describe limit values for specific physicochemical properties that are appropriate for identifying chemical substances that have no skin irritation or corrosion potential. These physicochemical properties include melting point, molecular weight, octanol-water partition coefficient, surface tension, vapour pressure, aqueous solubility and lipid solubility. Based on analyses of 1833 chemicals, physicochemical properties for limits were defined to determine that when a chemical's physicochemical properties were either greater or less than these limits that these chemicals would have no skin irritation or corrosion potential. To facilitate classification and labeling, the application domains of these limits were constructed to correspond with the European Union's risk phrases for chemicals classified for skin irritation/corrosion, viz., R 34, R35 or R38. This is the second paper of four companion papers. The first paper discussed mechanisms that can lead to significant skin irritation or corrosion after acute exposures to chemicals. The third paper described the application of structural alerts to identify chemical substances with skin irritation or corrosion potential. The fourth paper described the Skin Irritation Corrosion Rules Estimation Tool (SICRET), a user-friendly tool that allows non-(Q)SAR experts to identify chemical substances with skin irritation or corrosion potential based on physicochemical property limits and structural alerts. [source]