Showing papers on "Drug carrier published in 1982"

The targeting of drugs parenterally by use of microspheres.

Abstract: The use of microspheres as drug carrier systems is reviewed and discussed and specific details are given of recent work conducted as part of a joint program between the Schools of Pharmacy at Nottingham and Copenhagen. The physicochemical properties that influence the fate and deposition of colloidal particles following parenteral administration include particle size, surface charge, and surface hydropho-bicity. Adsorbed blood components also play a significant role. Drug targeting can be achieved in certain instances, although following intravenous administration, the major site of particle deposition is the liver. A relocation of the particles can be achieved by pharmaceutical formulation (e.g., coating with nonionic surfactants). In vivo experiments using the rabbit demonstrate the important characteristics of a model microsphere controlled release system based on DEAE-cellulose. The use of monoclonal antibodies as a coating agent to increase site specificity is also discussed.

Rate-controlled drug delivery.

Abstract: THE goal of pharmaceutical research is to find drugs with desirable therapeutic properties and low risks of undesirable side effects. Drugs with such high therapeutic ratios are usually sought as n...

Antitumor Effect of Ethylene-Vinyl Acetate Copolymer Matrices containing 5-Fluorouracil on Ehrlich Ascites Carcinoma in Mice

Abstract: Ethylene-vinyl acetate (EVA) copolymer was evaluated as a carrier for controlled release of 5-fluorouracil (5-FU). In order to study the effect of comonomer ratio modifications on the drug release kinetics, the release of 5-FU dispersed in polymer matrices composed of different ratios of ethylene and vinyl acetate was investigated. The vinyl acetate content of EVA copolymer was varied from 8 to 40% w/w. An increase in vinyl acetate comonomer content increased the drug release from the polymer matrix. The release rate could be controlled by modifying the ethylene/vinyl acetate ratios in the polymer matrices. The antitumor activity of EVA copolymer matrices containing 5-FU was evaluated against Ehrlich ascites carcinoma in mice, on the basis of changes in body weight and animal survival data. Tumor cell injections were performed on Day 0 and matrix implantations on Day 4, both intraperitoneally. The suppressive effect of matrices containing 5-FU on the increase in body weight was higher than that of the free drug. A prolongation of the life-span of tumor-bearing mice following implantation of therapeutic matrices was also noted. These results indicated that EVA matrices containing 5-FU may be effective in cancer chemotherapy. Matrices composed of EVA copolymer could be useful vehicles for implanted, inserted, or surface-applied delivery systems for anticancer agents.

Ocular Drug Delivery Systems - A Review

Abstract: New ocular drug delivery systems are currently receiving increased attention, in part because of the expected emergence of new drugs with short biological half-lives whose usefulness may depend on a more continuous drug supply than eyedrops can provide, and also in part because of the potential of some delivery systems to reduce the side effects of the more potent drugs recently introduced or presently under investigationSome ocular delivery systems extend the duration of drug action by enhancement of corneal absorption; these include soluble gels and emulsions, hydrophilic ocular inserts, ion-pair associations, prodrugs, and liposomes Other delivery systems provide for a controlled release of drugs; they can be based on any of several different mechanisms and include both erodible and nonerodible matrices The delivery systems are described in this review, along with their mechanisms, limitations, and the therapeutic rationale for their use

Drug Targeting with Monoclonal Antibodies

Abstract: A new approach to chemotherapy using monoclonal antibodies for drug targeting to the tumor cell is reported. Daunomycin was covalently bound to monoclonal antibodies directed against carcinoembryonic antigen with 0.01% glutaraldehyde. The pharmacological activity of the drug-antibody conjugate was assayed in vitro with human colon adenocarcinoma cells producing CEA. Using a drug: protein ratio of 5.7, the inhibition of thymidine incorporation was measured at various concentrations. At 500 ng/ml, the activity of antibody bound daunomycin was 800% the activity of an equivalent amount of free daunomycin; the activity of free antibody was only 2.2% while the physical addition of both antibody and daunomycin gave 116% of the activity of the free drug alone. A 60 minute incubation period of the conjugate with adenocarcinoma cells was sufficient to obtain this effect. This new approach offers a potential application in cancer treatment since the drug carrier is directed against an already used cancer marker.

Targeting of Liposomes: Study of Influencing Factors

Abstract: A decade has now elapsed since liposomes were first proposed1–3 as vehicles for drug delivery in biology and medicine. During this time extensive studies have revealed a multitude of uses4 and at the same time established many of the principles governing the system’s behaviour within the biological milieu.5–7 Among the advantages that liposomes offer as a drug carrier system, versatility in structural characteristics is most prominent. For instance, appropriate choice of lipid composition, size, surface charge and also of surface ligands that can recognise and associate with, target cells selectively can all profoundly influence the fate and behaviour of the carrier and thus contribute towards optimising the action of its drug contents. One of the major objectives in the use of liposomes in vivo is interaction with accessible cells i.e. those in the blood circulation, lining the capillaries and, in certain cases, cells in extravascular areas separated from the circulation by leaky membranes. There is, therefore, a need for drugs to be retained by the carrier for periods of time necessary for effective access to, and association with the target. Here we have attempted to understand factors that influence (a) quantitative retention of drugs by liposomes in vitro and in vivo (b) rates of liposome clearance from the circulation and (c) targeting of liposomes to specific cells.

Antibodies and Dextran as Anti-Tumour Drug Carriers

Abstract: The approach described herewith is an attempt to use antibodies directed towards tumor-associated antigens or other polymers or macromolecules, as carriers for cytotoxic anti-cancer agents in order to improve the effectiveness of cancer chemotherapy.

Hyperthermia-Mediated Targeting of Liposome-Associated Anti-Neoplastic Drugs

Abstract: One of the major obstacles limiting the effectiveness of chemotherapeutic programmes is the inability of the present drug inventory to discriminate normal from malignant neoplastic tissue. As the search for selective anticancer drugs has been largely ineffective to date, considerable research effort has been directed toward the development of drug carrier systems1. One of the systems being investigated are closed vesicles composed primarily of phospholipids2,3. Liposomes have been extensively used as models3,4 for biological membrane research and have contributed to understanding the physico-chemical properties of biological membranes6,7. They have also advanced our understanding of cell-cell recognition8,9, fusion10,11 and protein-lipid interaction12,13. The self-assembly properties of phospholipid amphiphiles make possible the entrapment of water soluble compounds within the aqueous lumen of the liposome14. It became evident that entrapment of enzymes within liposomes might provide a therapeutic vehicle useful in treatment of diseases of enzyme deficiency15,16.