Modified Plasma Proteins

Adamson RH, Clough G, 1992. Plasma proteins modify the endotheUal cell glycocalyx of frog mesenteric microvessels. / Physiol. 445 473. 

Purification. Hemoglobin is provided by the red blood ceU in highly purified form. However, the red ceU contains many enzymes and other proteins, and red ceU membranes contain many components that could potentially cause toxicity problems. Furthermore, plasma proteins and other components could cause toxic reactions in recipients of hemoglobin preparations. The chemical modification reactions discussed herein are not specific for hemoglobin and may modify other proteins as well. Indeed, multifimctional reagents could actually couple hemoglobin to nonhemoglobin proteins. 

Hydrophobically modified HA derivatives,91 obtained through the partial esterification of the HA carboxyl groups with methylprednisolone (45% in HYCp45 and 60% in HYCp60),92 have been deeply studied 93 A key point prior to any in vivo study of the biomaterial is the assessment of the so-called "stealth character" of the species itself. Such characteristic corresponds to be invisible towards the immune system, so that colloids are not recognized as foreign objects by body fluid components, as plasma proteins fibrinogen, BSA and lipidic components.94,95... 

Modified procedure (ASC kit) Ascorbic acid is isolated from plasma proteins and uric acid in a single-step liquid gel chromatography procedure and its amount... 

Proteins (e.g., modified plasma proteins, lysozyme, synthetic peptides, or peptide analogues) [260 - 262] ... 

Numerous problems in the construction of chnically applicable drug targeting moieties still need to be solved. Of these issues, immunogenicity after repeated administration, counterproductive hver clearance, and production 5delds are the most important. Although the problem of immunogenicity is beheved to have been solved for monoclonal antibody therapy by the development of humanized and fully human antibodies [110], for other carrier systems such as modified plasma proteins and peptide modified polymers, this remains an important issue. 

Figure 3. Step 1 in the modified MacFarland bioactivity model Diffusion or carriage by plasma protein from the entry point to the anterior membrane surface (ams) transfer from the first aqueous phase (0 ) to the ams passage through the membrane by diffusion or by lipid soluble membrane carrier molecule bound to the posterior membrane surface (pms) transfer from the pms to the second aqueous phase (02).

Gemfibrozil is absorbed quantitatively from the intestine and is tightly bound to plasma proteins. It undergoes enterohepatic circulation and readily passes the placenta. The plasma half-life is 1.5 hours. Seventy percent is eliminated through the kidneys, mostly unmodified. The liver modifies some of the drug to hydroxymethyl, carboxyl, or quinol derivatives. Fenofibrate is an isopropyl ester that is hydrolyzed completely in the intestine. Its plasma half-life is 20 hours. Sixty percent is excreted in the urine as the glucuronide, and about 25% in feces. 

Various natural, chemically modified and mixtures of flavonoids are widely used therapeutically as venous protective or venotonic drugs in chronic venous insufficiency and haemorrhoidal attacks. Flavonoids have been found to inhibit increased vessel wall permeability, fluid changes in the capillary bed and diffusion of plasma proteins. In addition, they may exert a protective effect on the perivascular tissues due to their antihyaluronidase effect and the inhibition of lysine oxidase (producing crosslinks in collagen and elastin) and lysosomal hydrolases (degrade glycosamines). All these effects may account for the venotonic effects of these drugs [5]. However, the venous effects of flavonoids are out of the scope of the present review. 

Tacrolimus is given orally (twice-daily dose regimen) or as an injection. A modified release (MR) oral dosage form of tacrolimus has been developed for administration once a day to overcome noncompliance, which is the major problem in acute graft rejection in solid transplant recipients. Tacrolimus is not completely absorbed by the GI tract and its rate of absorption could vary. It binds to plasma protein at a rate of 75-99% with a half-life of approximately 12 h and is predominantly metabolized in liver by CYP3A. Some of its metabolites have immunosuppressive activity. Most of the tacrolimus is excreted in feces, and a negligible amount (< 1%) is excreted in urine without undergoing any metabolism. 

---