Activity Of Oleic Acid Research Articles

Activity of Liposomal-Oleic Acid on Drug Resistant Strains of Pseudomonas aeruginosa Isolated from Clinical Specimens

Pseudomonas aeruginosa has rapidly developed resistance to multiple drugs throughout its antibiotic history and thus it is essential to develop novel antimicrobial strategies to minimize their resistance pattern. This study evaluated the antimicrobial activity of oleic acid (OA) in a liposomal formulation as a bactericidal drug against Multidrug Resistant Pseudomonas aeruginosa (MDRPa). Hence, we report the synthesis, characterization and the antimicrobial activity of liposomal oleic acids (LipoOA) against MDRPa. P. aeruginosa, isolated from pus on wound site and sputum from pulmonary infections were tested for its resistance against antibiotics by standard Kirby Bauer's disc diffusion method. Oleic acid (OA) in a liposomal formulation (LipoOA) was prepared by an extrusion method. Scanning electron microscopy (SEM) was utilized to monitor the surface morphology of LipoOA. The hydrodynamic size (diameter, nm), surface zeta potential (mV) of LipoOA and bare liposomes were measured using the Malvern Zetasizer. The encapsulation efficiency of OA in the synthesized LipoOA was determined using an LC-MS system. LipoOA were prepared to assess their antimicrobial activity against MDRPa. Encapsulation efficiency of OA in LipoOA was 33.7%. Strains were 100% resistance to cefepime and amikacin and 97.14% to to bramycin, ciprofloxacin and imipenem. Highly significant difference in LipoOA was observed for the clinical strain PS13 which exhibited an MIC of 1024 mg/L for amikacin and 512mg/L for cefepime by reducing the value to 67.4mg/L. In this study, therapeutic potential of liposomal oleic acids (LipoOA) against MDRPa was demonstrated. The synthesized LipoOA with diameter86.1 ± 0.5 nm fuses with bacterial membranes and subsequently releases the entrapped OA. Overall, this study highlights the promising possibility of using LipoOA as a new therapeutic option to the current antimicrobial strategies against MDRPa infections.

Polyunsaturated Branched-Chain Fatty Acid Geranylgeranoic Acid Induces Unfolded Protein Response in Human Hepatoma Cells.

The acyclic diterpenoid acid geranylgeranoic acid (GGA) has been reported to induce autophagic cell death in several human hepatoma-derived cell lines; however, the molecular mechanism for this remains unknown. In the present study, several diterpenoids were examined for ability to induce XBP1 splicing and/or lipotoxicity for human hepatoma cell lines. Here we show that three groups of diterpenoids emerged: 1) GGA, 2,3-dihydro GGA and 9-cis retinoic acid induce cell death and XBP1 splicing; 2) all-trans retinoic acid induces XBP1 splicing but little cell death; and 3) phytanic acid, phytenic acid and geranylgeraniol induce neither cell death nor XBP1 splicing. GGA-induced ER stress/ unfolded protein response (UPR) and its lipotoxicity were both blocked by co-treatment with oleic acid. The blocking activity of oleic acid for GGA-induced XBP1 splicing was not attenuated by methylation of oleic acid. These findings strongly suggest that GGA at micromolar concentrations induces the so-called lipid-induced ER stress response/UPR, which is oleate-suppressive, and shows its lipotoxicity in human hepatoma cells.

Oleic acid: its effects on stratum corneum in relation to (trans)dermal drug delivery.

Calorimetric studies with porcine stratum corneum (SC) have shown that the lipid phase transitions associated with the intercellular bilayers are markedly affected by treatment with oleic acid. Specifically, the transition temperatures (Tm) and cooperativity are reduced, whereas no effect was observed on the endotherm associated with keratin denaturation, suggesting that oleic acid primarily affects the SC lipids. The decrease in the lipid-associated Tm's was further correlated with the amount of oleic acid taken up by the SC. Parallel experiments with silastic implied that the uptake is dependent on the thermodynamic activity of oleic acid in the vehicle itself. The in vitro transport of Piroxicam across human and hairless mouse skin (HMS) was significantly enhanced by oleic acid, as a function of the extent of oleic acid uptake, with an attendant change in Tm. These results emphasize the role of SC lipids in percutaneous absorption. Transport also depended on the donor concentration of ionized drug suggesting that the enhanced transport mechanism cannot be accounted for solely on the principles of the classical pH-partition hypothesis. Accordingly, a model of skin permeability enhancement involving solid-fluid phase separation within the SC lipids is proposed for oleic acid, consistent with the existing phospholipid literature. In conjunction with the use of oleic acid as an enhancer, very soluble hydrophilic salts were recognized as key factors in attaining maximum delivery. Oleic acid uptake, lipid delta Tm, and enhanced drug flux were all found to correlate, exhibiting a bell-shaped curve as a function of the ethanol vehicle concentration. Therefore, uptake and/or DSC experiments are useful for formulating enhanced topical delivery systems.

De novo synthesis of lipids and incorporation of oleic acid into cultured human fibroblasts from diabetics and normal controls

The incorporation of [1− 14C]acetate and [1 − 14C]oleic acid into the lipids of cultured human fibroblasts derived from diabetics and age-matched normal controls has been studied at 5 m M and 30 m M glucose. Cells from diabetics incorporated significantly more activity from acetate into triglycerides at 30 m M glucose than at 5 m M. The controls showed no significant differences in acetate incorporation into any lipid class between the two glucose levels. The diabetics incorporated more acetate activity into cholesteryl esters than did the controls. Incorporation of [1− 14C]oleic acid activity into cellular lipids was higher at 30 m M glucose than at 5 m M in phospholipids and in all major classes of neutral lipids in both diabetics and controls.

Fatty acid-induced tuberculocidal activity in sera of guinea pigs treated with bacillus Calmette-Guérin and lipopolysaccharide.

This study showed that sera of guinea pigs immunologically activated by vaccination and by challenge with bacillus Calmette-Gu6rin (BCG) and sera of lipopolysaccharide (LPS)-treated guinea pigs have tuberculocidal activity. Like the tuberculocidal activity of oleic acid, the serum tuberculocidal activity was not neutralized by the addition of exogenous iron, but it was neutralized quite effectively by the addition of albumin. Both BCG- or LPS-induced tuberculocidal activities disappeared in about one week after treatment. Titrimetric determinations and gas-liquid chromatographic studies showed that the antibacterial activity in sera of immunologically stimulated animals is caused by the increased levels of myristic, palmitic, oleic, and linoleic acids. These fatty acids were found to be highly toxic for the BCG strain of Mycobacterium bovis. The tuberculocidal effect in sera of immunologically activated animals increases according to the number of previous vaccinations. This finding indicates that the antituberculous activity in serum is an expression of immunologic processes that take place in the body of sensitive animals during severe immunologic reactions. Some strains of Mycobacterium are unable to grow