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Showing papers on "Drug carrier published in 1976"


Journal ArticleDOI
24 Jun 1976-Nature
TL;DR: The results presented here indicate that uptake of vesicles containing AD by AD-resistant cells produces inhibition of cellular RNA synthesis and cell growth at AD concentrations that have no effect on cells when added as free drug to the culture medium.
Abstract: DEVELOPMENT of cellular resistance to actinomycin D (AD) has been reported in tumour cell populations in vivo1,2 and in vitro3–6 Such cells have a lower capacity than normal to incorporate AD3,6–8, prompting suggestions that the AD-resistant phenotype is determined by changes in plasma membrane function that reduce cellular permeability to this drug Support for this proposed mechanism of drug resistance has been provided by experiments showing that treatment of AD-resistant cells with membrane-active detergents, to increase plasma membrane permeability, enhances AD uptake by resistant cells and reduces the concentration of AD required to inhibit cell growth8,9 This approach, while instructive, has the disadvantage that the detergent causes significant alteration in cell viability and also impairs cell growth8 We now report a new method for enhancing drug uptake by permeability restriction, drug-resistant cells which uses lipid vesicles as carrier agents to introduce AD directly into cells As reported elsewhere10,11, negatively-charged lipid vesicles composed of lipids or lipid mixtures that are “fluid” at 37 °C are incorporated into cultured cells by fusion with the cellular plasma membrane Entrapment of drugs inside such vesicles and subsequent fusion of the vesicles with cells offers a potential method for bypassing the plasma membrane transport barrier to introduce drugs directly into the intracellular compartment Since vesicles are not cytotoxic10–12, their use as drug carriers allows direct evaluation of the cellular response to the introduced drug, free from the complications8,9,13 associated with the use of detergents The results presented here indicate that uptake of vesicles containing AD by AD-resistant cells produces inhibition of cellular RNA synthesis and cell growth at AD concentrations that have no effect on cells when added as free drug to the culture medium

50 citations


Journal ArticleDOI
TL;DR: It is suggested that the pharmacist study the release pattern of drug devices and the pharmaceutics of prodrugs in order to maintain his responsibility as the expert on drugs.
Abstract: Recent developments in the area of drug delivery are reviewed. Controlled delivery of drug substances (including controlled-release oral products, the Folkman-Long silastic device and membrane-medicated delivery systems) are discussed. The prodrug approach is illustrated by discussion of the esterification of epinephrine and the production of the dihydro form of 2-PAM (pro-2-PAM). It is suggested that the pharmacist study the release pattern of drug devices and the pharmaceutics of prodrugs in order to maintain his responsibility as the expert on drugs.

4 citations


Book ChapterDOI
01 Jan 1976
TL;DR: The use of carrier linked drug-antibody conjugates (‘carrier-DRAC’) in the mouse EL4 lymphoma system is described as a model for selective transport of cytotoxic drugs in cancer therapy.
Abstract: The use of carrier linked drug-antibody conjugates (‘carrier-DRAC’) in the mouse EL4 lymphoma system is described as a model for selective transport of cytotoxic drugs in cancer therapy. This method of conjugation provides for a high degree of drug substitution without significant loss of antibody activity and with no loss of water solubility. Suppression of tumour growth in vivo, and tests in vitro show greater effectiveness of the drug-carrier-antibody conjugate than of drug-carrier and antibody uncombined.

3 citations