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Lipid-drug conjugates (LDC), which may also be addressed as lipoidal prodrug, have the therapeutic actives chemically bound to a lipid moiety like fatty acids or phospholipids. ...Fabricated in nano-size, lipid-drug conjugate forms another breed of lipid nanoparticles. LDCs are prepared in order to increase the drug loading and hence prevent leakage of a highly polar drug from a lipophilic matrix. In turn, it assists to achieve active targeting of therapeutics with reduced side effect by altering the pharmacokinetic profile of the drug. These self-assembled systems take the benefit of metabolic pathways of lipid biochemistry, allowing suitable organ targeting depending upon its size. These lipids because of its similarities with physiological lipids, enhances the solubility of the therapeutic agents and thereby improve the bioavailability. This present review is meant to encompass different aspects related to lipid drug conjugates which include types of lipids and drugs that can be used to develop this type of formulation. Here, we throw light on methods of preparation of lipid drug conjugate, processing them into nanoparticle, its characterization and different applications of lipid drug conjugate. We aim to present a holistic view on lipid drug conjugate as a suitable drug delivery approach.
Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil may prevent development of heart failure through alterations in cardiac phospholipids that favorably ...impact inflammation and energy metabolism. A high-fat diet may block these effects in chronically stressed myocardium. Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to pressure overload by constriction of the abdominal aorta. Animals were fed: (1) standard diet (10% of energy from fat), (2) standard diet with EPA+DHA (2.3% of energy intake as EPA+DHA), (3) high fat (60% fat); or (4) high fat with EPA+DHA. Pressure overload increased LV mass by approximately 40% in both standard and high-fat diets without fish oil. Supplementation with fish oil increased their incorporation into cardiac phospholipids, and decreased the proinflammatory fatty acid arachidonic acid and urine thromboxane B(2) with both the standard and high-fat diet. Linoleic acid and tetralinoloyl cardiolipin (an essential mitochondrial phospholipid) were decreased with pressure overload on standard diet, which was prevented by fish oil. Animals fed high-fat diet had decreased linoleic acid and tetralinoloyl cardiolipin regardless of fish oil supplementation. Fish oil limited LV hypertrophy on the standard diet, and prevented upregulation of fetal genes associated with heart failure (myosin heavy chain-beta and atrial natriuetic factor). These beneficial effects of fish oil were absent in animals on the high-fat diet. In conclusion, whereas treatment with EPA+DHA prevented tetralinoloyl cardiolipin depletion, LV hypertrophy, and abnormal genes expression with pressure overload, these effects were absent with a high-fat diet.
Regional distribution of tocopherols and fatty acids within three soya beans was investigated by high-performance liquid chromatography and gas–liquid chromatography, respectively. Tocopherols were ...predominantly detected in axis, followed by cotyledons and seed coat. Dominant components were
γ- and
δ-tocopherols, with much smaller amounts of
α- and
β-tocopherols. However,
α-tocopherol was higher (
P<0.05) in axis than other tissues. Triacylglycerols (TAGs) were the major component of total lipids, representing 92.0% in cotyledons and 70.0% in axis or coat. A small difference (
P<0.05) occurred in fatty acid profile of TAGs when comparing seed coat to the axis. The fatty acid composition of phosphatidyl inositol differed (
P<0.05) from phosphatidyl ethanolamine and phosphatidyl choline in each tissue. These results indicate that the differences in soya bean cultivars would be appreciable, based on the distribution of tocopherols and fatty acids in each component part within soya bean seeds.
To evaluate the influence of intraperitoneal treatment with phospholipids on the formation of peritoneal carcinosis after inoculation of colonic tumor cells in rats. The presence of tumor cells in ...the peritoneal cavity serves as a prognostic marker for postoperative survival after resection of gastrointestinal cancer. Intraperitoneal tumor cell attachment is a pivotal step in developing peritoneal carcinosis. Intraabdominal application of phospholipids resulted in a significant decrease of adhesion formation, especially at sites of peritoneal lesions.
2x10(6) colonic tumor cells (DHD/K12/TRb) were injected intraperitonely in female BD-IX rats. A total of 90 rats were divided into three groups with treatments of phospholipids at 75 mg/kg or 150 mg/kg bodyweight or sodium chloride at 0.9% in the control group. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of tumor attachment and the Peritoneal Cancer Index. Over a 90-day observation period, the survival rate was analyzed. In vitro, we examined the reduction of tumor cell adhesion on extracellular matrix components after treatment with phospholipids. Microtiter plates were coated with laminin, fibronectin or collagen IV for adhesion experiments.
In our study, we found a significant reduction of peritoneal dissemination with respect to all evaluation methods after treatment with phospholipids at 150 mg/kg in animals without peritoneal lesions. This could not be achieved using the lower concentration of phospholipids (75 mg/kg). In vitro, the maximum reductions of tumor cell adhesion by phospholipids compared with the control values for laminin and fibronectin were 46% and 37%, respectively, whereas for collagen IV the reduction was only 24% ( p<0.0001).
A new method of prevention of intraperitoneal tumor cell adhesion, possibly leading to a reduced incidence of peritoneal carcinosis after surgery of gastrointestinal tumors, is introduced.
Platelet activating factor is one of the most potent inflammatory ether phospholipid mediators known and structurally modified analogues are of considerable interest as potential therapeutic ...preparations. Inspired by the proposed structure for a novel endogenous hydroxy-PAF analogue isolated recently from gingival crevicular fluid, we designed and prepared two novel steroid-modified ether phospholipids. These two novel compounds exhibit marked chemical and biological similarities to their endogenous prototype and they antagonize it being less active in inducing washed platelet aggregation through PAF receptors.
`Granny Smith' apples (
Malus domestica Borkh) were wounded with a hypodermic needle or not prior to cold storage for 7 months at 0°C. Wounded apples did not develop superficial scald adjacent to the ...wounded areas while non-wounded tissue developed scald on greater than 60% of the apple surface. Changes in conjugated trienes (CT) and membrane lipids that occurred as a result of scald formation were measured by examination of non-scalded tissue (achieved via wounding), scalded tissue on the same apple, and/or scalded tissue on the control fruit. Scald development was associated with an increase in CT and total glycolipid (GL) content, and a decrease in the proportion of linolenic acid (18:3) of the GL fraction and the GL unsaturation index (UI). These changes indicate that the chloroplast membrane is most affected by scald formation, possibly by the oxidative effect of CT. The reason for scald inhibition in the wound vicinity remains unknown. The increase in cinnamic acid derivatives in the wound area suggests an antioxidant activity.
During breathing, the pleural surfaces slide against each other continuously without damage. Pleural liquid and lubricating molecules should provide the lubrication of the sliding surfaces, thus ...protecting the mesothelium from shear-induced abrasion. D’Angelo et al. (Respir. Physiol. Neurobiol. 2004) measured the coefficient of kinetic friction (μ) of rabbit parietal pleura sliding against visceral pleura in vitro at physiological velocities and under physiological loads; it was ~0.02 and did not change with sliding velocity, consistent with boundary lubrication. μ in boundary lubrication can be influenced by surface molecules like hyaluronan, sialomucin or surface active phospholipidis. Hyaluronan or sialomucin is able to restore good boundary lubrication in damaged mesothelium. Nevertheless, hyaluronidase and neuraminidase treatment of the mesothelium does not increase μ, though neuraminidase cleaves sialic acid from the mesothelium. Short pronase or phospholipase treatment, so as to affect only the mesothelial glycocalyx, increases μ, and this increase is removed by hyaluronan or sialomucin. On the other hand, addition of phospholipids after phospholipase treatment produces a small effect relative to that of hyaluronan or sialomucin, and this effect is similar with unsaturated or saturated phospholipids. In damaged mesothelium, the lubrication regimen becomes mixed, but addition of hyaluronan or sialomucin restores boundary lubrication.
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