Carrier-systems

L. Fiume, C. Busi, A. MattioH, and G. Spiuosa, CRC Critical Reviews in Therapeutic Drug Carrier Systems 4, 265—284 (1988). 

I. Gonda, Crit. Rev. Ther. Drug Carrier Systems 6, 273—313 (1990). 

Container carrier systems. Container carrier systems are being used in a limited number of cases, the most important of which are (1) the collection of wastes from only a few pickup points at which a considerable amount of waste is generated and (2) the collection of bulky items and industrial rubbish not smtable for collection with compaction vehicles, and (3) small, heavy loads such as scrap metal. 

Carriers and channels may be distinguished on the basis of their temperature dependence. Channels are comparatively insensitive to membrane phase transitions and show only a slight dependence of transport rate on temperature. Mobile carriers, on the other hand, function efficiently above a membrane phase transition, but only poorly below it. Consequently, mobile carrier systems often show dramatic increases in transport rate as the system is heated through its phase transition. Figure 10.39 displays the structures of several of these interesting molecules. As might be anticipated from the variety of structures represented here, these molecules associate with membranes and facilitate transport by different means. 

The kinetic scheme applicable to the Valinomycin carrier system is given in Fig. 18 where S is the carrier and MS+ is the carrier-cation complex. There are five unknown parameters, the four rate constants and Ns, the interfacial concentration of... 

Couvreur, P., Barratt, G., Fattal, E., Legrand, P. Vauthier, C. (2002). Nanocapsule technology A review. Critical Reviews in Therapeutic Drug Carrier Systems, Vol. 19, 2, (March 2002), pp. (99-134), ISSN 0743-4863... 

Since our backbone 2 aPNA incorporates six Lys residues in its peptide sequence and is cationic at a physiological pH, we were optimistic that this aPNA would be taken up into cells without the need for any external carrier system. To answer the simple question of whether b2 aPNAs are intemahzed, a standard fluorescence microscopy experiment was performed to see if whole cells that were incubated with a fluorescent-labeled aPNA would internahze labeled material [70]. Chinese Hamster Ovary (CHO) cells in culture were incubated with BODIPY-la-beled TCCCT(b2) at 37 °C for various periods of time. Following incubation, the cells were rinsed in phosphate-buffered sahne (PBS), fixed with 4% formaldehyde at ambient temperature for 20 min, then washed with PBS and stored in a refrigerator until examined by fluorescence microscopy. 

Liposomes have been widely used as model membranes and their physicochemical properties have therefore been studied extensively. More recently, they have become important tools for the study of membrane-mediated processes (e.g., membrane fusion), catalysis of reactions occurring at interfaces, and energy conversion. Besides, liposomes are currently under investigation as carrier systems for drugs and as antigen-presenting systems to be used as vaccines. 

One approach where the characteristics of the liposomal carrier system are well matched to the intended therapeutic application is the delivery of drugs to the MPS. Because of their particulate nature, the major route of clearance of liposomes, when administered in vivo by a variety of routes, is phagocytosis by MPS cells, especially macrophages in liver and spleen. Obviously, this "natural" fate of liposomes in vivo is an advantage if one attempts to treat diseases... 

A notable property of liposomes, which has not been appreciated enough, is the presence of water inside liposomes. This makes them an excellent delivery system for biotechnologically engineered proteins with tertiary and quanternary structures which are sensitive to irreversible damage induced by dehydration, as often occurs with alternative, particulate carrier systems. 

Gabizon, A. (1989). Liposomes as a drug delivery system in cancer chemotherapy, in Drug Carrier Systems Horizons in Biochemistry and Biophysics, Vol. 9 (F. H. Roerdink and A. M. Kroon, eds.), John Wiley and Sons, Chichester, pp. 185-211. 

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

Modem oil spill-dispersant formulations are concentrated blends of surface-active agents (surfactants) in a solvent carrier system. Surfactants are effective for lowering the interfacial tension of the oil slick and promoting and stabilizing oil-in-water dispersions. The solvent system has two key functions (1) to reduce the viscosity of the surfactant blend to allow efficient dispersant application and (2) to promote mixing and diffusion of the surfactant blend into the oil film [601]. 

The formulation of a defoamer should be suitable for a prolonged storage time before use. A carrier system makes the defoamer easy to handle and dispersible for delivering the active defoamer components to the foaming system and also to stabilize the defoaming formulation. 

The above conclusion is supported by the results shown in figure 4. Just as inhibitors of the 5-HT uptake carrier can antagonize MDMA-induced [ H]5-HT release in vitro, coadministration of MDMA with an uptake inhibitor such as citalopram can completely block the acute depletion of 5-HT. Although citalopram also antagonized the MDMA-induced decrease in TPH activity, there was still a significant loss of enzyme activity when compared to control. This implies that if MDMA requires access to the interior of the nerve terminals to affect TPH activity, it does not require the activity of the uptake carrier to gain entrance. Hence, these results are consistent with the outcome of synaptosomal uptake experiments with [ HJMDMA (Schmidt et al. 1987), which show that MDMA is not actively concentrated by a carrier system. Furthermore, it is apparent that the loss of enzyme activity alone is not sufficient to reduce 5-HT concentrations, but that release via the carrier must occur simultaneously, to deplete the terminal once synthetic capacity is reduced. 

Probably the most promising polymeric drug carrier system involves polysaccharide molecules. These are natural polymers and are often biodegradable to products that are useful to the host or easily eliminated by the host. Dextrans have been the most extensively used polysaccharide for macromolecular prodrug preparations (79). These materials are biocompatible and the in vivo fate is directly related to their molecular weight. Moreover these macromolecules can be easily targetted to the hepatocytes with D-mannose or L-fucose (20). 

C Duverne, A Bouten, A Deslandes, J-F Westphal, J-H Trouvin, R Farinotti, C Carbon. Modification of cifixime bioavailability by nifedipine in humans involvement of the dipeptide carrier system. Antimicrob Agents Chemother 36 2462-2467, 1992. 

The advantageous effects of liposomal carrier systems include protection of compounds from metabolism or degradation, as well as enhanced cellular uptake. Liposome-mediated delivery of cytotoxic drugs to cells in culture has resulted in improved potency [58,59]. Prolonged release of encapsulated cargo has also been demonstrated [60,61]. More recently, liposomes with extended circulation half-lives and dose-independent pharmacokinetics (Stealth liposomes) [62] have shown promise in delivery of drugs that are normally very rapidly degraded. 

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