Drugs Carrier-Bound

A special group of carrier-linked prodrugs are the site-specific chemical delivery systems [23], Macromolecular prodrugs are synthetic conjugates of drugs covalently bound (either directly or via a spacer) to proteins, polypeptides, polysaccharides, and other biodegradable polymers [24],... 

Qualitative analysis of intrahepatic distribution is possible with immunohistochemistry. With antibodies against the carrier or the carrier-bound drug this compound can be localized in liver sections [152],To identify the cell type(s) involved in the uptake, the sections can subsequently be double stained with markers for the different cell types. In the rat liver, the monoclonal antibodies HIS52 (anti-rat endothelial cell antigen-1 or anti-RECA-1), ED2, the combination of anti-desmin and anti-glial fibrillary acidic protein, and anti-aSMA are generally used to identify SECs, KCs, quiescent HSCs, and activated HSCs, respectively. 

Rihova, B., and Riha, I. Immunological problems of polymer-bound drugs. Crit. Rev. Ther. Drug Carrier Syst. 1 311-374, 1985. 

POTENTIAL USEFULNESS OF CELL MEMBRANE-BOUND ENZYME SUBSTRATES AND INHIBITORS, AND CELL MEMBRANE-BOUND RECEPTOR AGONISTS AND ANTAGONISTS AS DRUG CARRIERS WITH LUNG SPECIFICITY... 

Treatment of H35 cells with MTX-BSA. The comparative growth rates of H35 cells plated at 2 x 10 cells/dish in the presence of various levels of MTX-BSA are shown in Table I. Clearly the growth of wild-type cells is retarded by micromolar quantities of MTX-BSA with 40 pM MTX-BSA leading to a complete cessation of growth. The H35R (see EXPERIMENTAL for subscript definition) cells, however, are unaffected by this concentration of carrier-bound drug and demonstrate a growth response comparable to that of the untreated H35 cells. 

Experiments which examine the comparative toxicities of the poly-L- and -D- carriers for hepatocytes and hepatomas indicate a low level of toxicity with the hepatoma. However, an elevated toxic effect is observed for the hepatocyte with the D-isomeric carrier. When the drug is bound to the carrier little alteration is observed in the toxic response of the hepatocyte suggesting that in its resting state it has little requirement for dihydrofolate reductase. The results shown in Table 111 illustrate this point more clearly where only 26Z of reductase activity remains after treating the hepatocytes with 2 micromolar MTX(poly-L-lyaine) yet 752 cellular viability resiains. This contrasts with the response of the hepatoma cell line (Table IV), where both dihydrofolate reductase and 90Z cell growth of both transport defective and non-defective cell lines is eliminated by treatment with 2.8 micromolar MTX(poly-L-lysine). 

Figure 35.7 Structure of the drug carrier human serum albumin. Seven hydrophobic molecules (in red) are shown bound to the molecule. [Drawn from IBKE.pdb.]... 

A chemical reaction takes place at the interface between the drug carrier and the external solution sometimes bioerosion of the polymer carrier takes place, whereas in other cases the drug is covalently bound to the carrier and is dissolved by breaking of such bonds. 

Incubation of nanoparticles with cells in media leads to adsorption of serum proteins on their surface that increases the entry of nanoparticles into the cells by receptor-mediated endocytosis. However, during in vivo applications, designed nanoparticles can facilitate clearance by the reticuloendothelial system (mononuclear phagocyte system) because of serum proteins on the nanoparticle surface. Macrophages located in the liver and spleen remove nanoparticles bound with serum proteins (fibronectin, laminin, etc.). Binding of plasma protein is the first step for RES to remove the circulating nanosized drug carrier systems within a few hours. 

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