Showing papers on "Drug carrier published in 1979"

Magnetically responsive microspheres and other carriers for the biophysical targeting of antitumor agents.

Abstract: Publisher Summary This chapter has compared the major encapsulation carriers that have been tested for targeting of antitumor agents. A new, nontoxic carrier system was introduced for the in vivo localization of these agents. This consisted of magnetically responsive small albumin microspheres that are injected intra-arterially and localized at specific target sites by the application of appropriately directed magnetic fields. The new drug delivery vehicle could be targeted much more efficiently than any other type of nonmagnetic encapsulation carrier. It appears to have overcome the major problem characteristic of encapsulation carriers—namely, their rapid clearance by organs of the reticuloendothelial system. This preparation has the additional advantage of affording various rates of drug release that can be tailored to in vivo requirements. A prototype drug, adriamycin, was encapsulated and was found to distribute with the carrier. The released drug retained its biological activity. The relative advantages and disadvantages of encapsulation carriers, and exposed drug carriers were compared. Based on a high efficiency of targeting, magnetically responsive albumin microspheres appear to represent the optimal currently available vehicle for delivery of antitumor agents to regionally localized tumors with well-defined blood supplies. Although, there are still significant problems attending their uses as carrier systems, specific antitumor antibodies appear to represent the best currently available approach to the treatment of widely disseminated tumors. A hybrid approach, involving two-stage delivery, was discussed as a potential method for further augmenting the efficiency of drug targeting.

Drug-carrier Property of Albumin Microspheres in Chemotherapy. II. Preparation and Tissue Distribution in Mice of Microsphere-entrapped 5-Fluorouracil

Abstract: Bovine serum albumin microspheres contatining 5-fluorouracil-6-3H were prepared by heating at 180° (or 150°, 100°) of 25% albumin solution in cottonseed oil emulsion. The shape of this microsphere was invariably spherical, and the average diameter was 0.66μ. After intravenous injection in mice, 5-fluorouracil-6-3H entrapped in albumin microspheres localized mainly in the liver, and the disappearance rate of radioactivity in microspheres from the tissue was very slow in comparison with that of free drugs. The microsphere might be delivered into reticuloendothelial system in the liver because ofits phagocytic activity, as well as the distribution following injection of albumin macroaggregates. Such preferential localization and sustained release of entrapped drugs suggested that albumin microspheres are useful as drug-carrier in chemotherapy.

Drug-carrier property of albumin microspheres in chemotherapy. iii. effect of microsphere-entrapped 5-fluorouracil on ehrlich ascites carcinoma in mice

Abstract: To examine the possibility of utilizing albumin microspheres as drug-carriers, an in vitro release of 5-fluorouracil (5-FU) from albumin microspheres was examined and the effect of intraperitoneally injected drug-carrying microspheres on Ehrlich ascites carcinoma in mice was studied. In vitro release characteristics determined by dialysis experiments showed that 5-FU release continued over one week. We also noted that drug release in the peritoneum of ascites-bearing mice continued over one week and that their life-span increased. Furthermore, the microspheres were phagocytized in vivo by the ascites cells. Our results suggest that albumin microspheres containing 5-FU may represent an effective system of drug delivery with prolonged action.

Potential of liposomes as drug-carriers in cancer chemotherapy: a review.

Abstract: Liposomes are bilayered phospholipid vesicles that have been proposed as vehicles for the selective delivery of cytotoxic drugs into malignant cells. In vitro and in vivo experiments have indicated that the activity of a range of drugs or their active metabolites may be enhanced by encapsulation in liposomes, particularly when used against drug-resistant tumours. Moreover, liposomal entrapment certainly has a marked effect on the tissue distribution and rates of clearance of cytotoxic drugs, and also appears to reduce their toxicity in most cases. However, in both animal and patient studies the major sites of uptake following IV administration consistently appear as the liver and spleen. Preferential tumour uptake has therefore not yet been achieved, although a degree of localization of liposomal labels can be demonstrated in the vicinity of experimental animal tumours in certain circumstances. Liposomes may have a future role in cancer chemotherapy, but much laboratory work remains to be done before clinical application can be considered.

Chapter 24 Liposomes as Drug Carriers

Abstract: Publisher Summary This chapter summarizes the charactristic features of liposomes and their role as drug carriers. Liposomes are vesicles composed of one or more lipid bilayers completely surrounding an internal aqueous space. The concept behind the use of liposomes as carriers of drugs and macromolecules is related to an expected protection of the encapsulated molecules in the blood stream. The initial observations on the ability of liposomes to induce cell fusion generated interest on the question as to whether liposomes could fuse with the cellular plasma membrane. The permeability of liposomes is an important parameter that depends not only on the innate properties of the lipid bilayer and the encapsulated material, but also on the interaction of liposomes with plasma components and various cells. Other in vivo studies with antibody bearing liposomes have also been reported in this chapter. The role of liposome structure on their (relatively limited) ability to enhance oral absorption of drugs and localization of the contents of positively charged liposomes in arterial lesions has been reported recently. The interaction of liposomes with various plasma components is an important parameter not only in relation to their permeability but also in defining the chemistry of the surface groups available for interaction with cells in various tissues. Localization of intact liposomes, especially in interstitial spaces in various tissues, may not necessarily be accompanied by the release of the vesicle contents into intracellular spaces where the drug could act. The effects of various pharmacological agents encapsulated in liposomes have been reviewed recently. However, liposomes were developed originally as a model membrane system and not as drug carriers. It seems clear that the ultimate utility of liposomes as drug carriers will depend largely on further methodological developments and a better understanding of their interactions with cells.

The concept of drug-carriers in the treatment of parasitic diseases.

Abstract: In many parasitic diseases, the reticulo-endothelial system is the major site of infection. Linking antiparasitic drugs to macro-molecular carriers may therefore extensively improve their therapeutical properties. The drug-carrier complex is no longer able to diffuse through the cell plasma membranes, and will be taken up preferentially by the cells which display high endocytic capacity. Complexed drugs will also be excreted at lower rate than free drugs, leading to increased plasma levels, for prolonged periods. Not the least, cells with low or no endocytic activity will be protected from adverse action of the drug, thus improving the overall therapeutic index of the complex with regard to the free drug.