Lipids drugs and

The preparation of nanoparticles by precipitation from an organic solution is well known from the preparation of polymeric nanocapsules and can also be used for the SLN production. The lipid, drug and the stabilizer(s) are dissolved in a water-miscible organic solvent (e.g. acetone, ethanol) or solvent mixture and this solution is dropped in the stirred aqueous phase that may contain a hydrophilic surfactant. Chen et al. firstly evaporated a part of the solvent mixture at elevated temperature before injection into the cooled aqueous phase under stirring. ... 

In many individuals, hyperlipidemia has no symptoms and the disorder is not discovered until laboratory tests reveal elevated cholesterol and triglyceride levels, elevated LDL levels, and decreased HDL levels. Often, these drags are initially prescribed on an outpatient basis, but initial administration may occur in the hospitalized patient. Seram cholesterol levels (ie, a lipid profile) and liver functions tests are obtained before the drugs are administered. 

Fig. 4 Concentrations (ng L ) of the most ubiquitous analgesics and anti-inflammatories, lipid regulators, psychiatric drugs and [I-blockers detected in (a) wastewater effluents and (b) river water downstream of the three WWTP in the Ebro river basin in relationship to the dilution factor...

Adamantane derivatives can be employed as carriers for drug delivery and targeting systems. Due to their high lipophUicity, attachment of such groups to drugs with low hydrophobicity could lead to a substantial increase of drug solubihty in lipidic membranes and thus increases of its uptake. 

Generally it is only the non-dissociated or unionised drug that is lipid-soluble and a drug s degree of ionisation depends on its dissociation constant (pA) and the pH of the environment in which it finds itself. For an acidic drug this is represented by the Henderson Hasselbalch equation as... 

Blocking the conversion to DA would appear stupid unless this could be restricted to the periphery. More dopa would then be preserved for entry into the brain, where it could be decarboxylated to DA as usual. Drugs like carbidopa and benserazide do precisely that and are used successfully with levodopa. They are known as extracerebral dopa decarboxylase inhibitors (ExCDDIs). Carbidopa (a-methyldopa hydrazine) is structurally similar to dopa but its hydrazine group (NHNH2) reduces lipid solubility and CNS penetration (Fig. 15.4). 

As with urine, saliva (spumm) is easy to collect. The levels of protein and lipids in saliva or spumm are low (compared to blood samples). These matrices are viscous, which is why extraction efficiency of xenobioties amoimts to only 5 to 9%. By acidifying the samples, extraction efficiencies are improved as the samples are clarified, and proteinaceous material and cellular debris are precipitated and removed. Some xenobioties and their metabohtes are expressed in hair. Hair is an ideal matrix for extraction of analytes to nonpolar phases, especially when the parent xenobioties are extensively metabolized and often nondetectable in other tissues (parent molecules of xenobioties are usually less polar than metabolites). Hair is a popular target for forensic purposes and to monitor drug compliance and abuse. Human milk may be an indicator of exposure of a newborn to compounds to which the mother has been previously exposed. The main components of human milk are water (88%), proteins (3%), lipids (3%), and carbohydrates in the form of lactose (6%). At present, increasing attention is devoted to the determination of xenobioties in breath. This matrix, however, contains only volatile substances, whose analysis is not related to PLC applications. 

Kaneko et al. (1993) have described a group of lipophilic ascorbic-acid analogues that have been studied in cultured human umbilical vein endothelial cells that were first incubated with test drug and then exposed to lipid hydroperoxides. Although ascorbate itself did not protect the endothelial cells, derivatives like CV3611 protected. Pretreatment was necessary. CV3611 was synergistic with vitamin E. The authors concluded that these lipophilic antioxidants incorporate into endothelial cell membranes where they are effective inhibitors of lipid peroxidation. In contrast, lipophobic antioxidants were not effective in their hands (Kaneko et al., 1993). 

Lipid Bilayers in Cells Implications in Drug and Gene Delivery T. Marjukka Suhonen, Pekka Suhonen, and Arto Urtti... 

TABLE 4 Magnetic Properties of Atomic Nuclei Used for the NMR Study of Lipid Bilayers and Drug Delivery... 

In this section, we focus on how to determine DD sites by NMR. The specification of the DD sites in bilayers can be done by utilizing the NMR signals of both drugs and membrane lipids. An example of the delivery site determination is given for the case of two benzene derivatives, propylbenezene (PrBe) and benzyl alcohol (BzOH) in egg phosphatidylcholine (EPC) bilayers [46]. Alkylbenzenes are suspected to be endocrine disruptors, and BzOH is one of the local anesthetics. 

We have also determined the delivery sites of alkylbenzenes by NMR. As already described in Section III.A, PrBe are deeply transported to the chain tail region in the bilayer core and the delivery site can be classified into category III [46]. Benzene, however, cannot deeply penetrate into the hydrophobic core, zone III, but is trapped preferentially at the interfacial site of the bilayer, zone II the delivery site can be classified into category II. Although benzene is generally considered to be hydrophobic, the delivery site of benzene determined by NMR is reasonable in the sense of the 7r-electrons with some affinity for the hydrophilic sites of the bilayer. Both drug and lipid sides of the H NMR spectra show that alkylbenzenes can deeply penetrate into the bilayer interior in the order PrBe > ethylbenzene > toluene > benzene, which is consistent with the sequence of the insolubility in water. 

Lipid Bilayers in Cells Implications in Drug and Gene Delivery... 

This review gives an overview of the structure of the lipid bilayers and their role in limiting drug delivery. 

Amphipathic peptides contain amino acid sequences that allow them to adopt membrane active conformations [219]. Usually amphipathic peptides contain a sequence with both hydrophobic amino acids (e.g., isoleucine, valine) and hydrophilic amino acids (e.g., glutamic acid, aspartic acid). These sequences allow the peptide to interact with lipid bilayer. Depending on the peptide sequence these peptides may form a-helix or j6-sheet conformation [219]. They may also interact with different parts of the bilayer. Importantly, these interactions result in a leaky lipid bilayer and, therefore, these features are quite interesting for drug delivery application. Obviously, many of these peptides are toxic due to their strong membrane interactions. 

Certain drugs and diseases can cause abnormalities in serum lipids and should be evaluated (Table 9-3). Every effort should... 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

The ocular hypotensive lipids in typical ophthalmology practice are considered first-line alternatives to topical P-blockers because of their superior efficacy and safety profiles. Many clinicians may choose to use the ocular hypotensive lipids as first-line agents, especially in patients that have an initial requirement to lower IOP by more than 25%, or in patients that have relative or absolute contraindications to topical P-blockers. However, latanoprost is currently the only ocular hypotensive lipid drug that has a Food and Drug Administration (FDA) indication for first-line therapy. Bimatoprost and travoprost are indicated by the FDA for patients who are intolerant of other IOP-lowering therapy or insufficiently responsive to another IOP-lowering medication.10,38... 

In this work we will focus on the use of the cubic phase as a delivery system for oligopeptides - Desmopressin, Lysine Vasopressin, Somatostatin and the Renin inhibitor H214/03. The amino acid sequences of these peptides are given in Table I. The work focuses on the cubic phase as a subcutaneous or intramuscular depot for extended release of peptide drugs, and as a vehicle for peptide uptake in the Gl-tract. Several examples of how the peptide drugs interact with this lipid-water system will be given in terms of phase behaviour, peptide self-diffusion, in vitro and in vivo release kinetics, and the ability of the cubic phase to protect peptides from enzymatic degradation in vitro. Part of this work has been described elsewhere (4-6). 

Lipid Microspheres and Lecithinized-Polymer Drug Delivery Systems... 

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