Showing papers on "Drug carrier published in 1983"

Site–Specific (Targeted) Drug Delivery in Cancer Therapy

Abstract: The current status of efforts to target cytotoxic agents to tumor cells using antitumor antibodies and particulate drug carriers such as liposomes and microspheres is reviewed. Emphasis is given to the role of anatomic and physiologic factors in determining the disposition, fate, and therapeutic efficacy of targeted drug delivery systems and to the importance of tumor cell heterogeneity as a major obstacle to effective cancer therapy.

Improved therapeutic benefits of doxorubicin by entrapment in anionic liposomes.

Abstract: When used as drug carriers, anionic liposomes can reduce the chronic cardiac toxicity and increase the antileukemic activity of doxorubicin (DXN; Adriamycin). Continuing investigations, reported here, have now established the therapeutic benefits of this mode of drug delivery. Liposome encapsulation caused a prolonged elevation in DXN plasma levels and a 2-fold reduction in the exposure of cardiac tissue to the drug. This reduction, however, was not proportional to the substantial decrease in chronic heart toxicity observed in the earlier study. In vivo studies have demonstrated that the entrapped drug retains its full activity against Sarcoma 180 and significantly increases its action against Lewis lung carcinoma, as measured by reduced tumor volume. The increased antineoplastic activity was again not proportional to the increased association of drug with tumor tissue. The effect of liposome entrapment on the immune-suppressive activity of DXN was also examined to determine if factors other than the direct delivery of drug to tumor tissue might improve the therapeutic response. The suppression of the humoral immune response and peripheral leukocyte counts by free DXN was nearly abolished when the drug was administered in the liposome form. These experiments suggest that the improved therapeutic effect of encapsulation may be the outcome of three different mechanisms: (a) altered disposition into subcellular compartments, which reduces cardiotoxicity; (b) increased plasma drug exposure to tumor cells; and (c) significant reduction in the immune suppressive activity of DXN.

Preparation and properties of a drug-carrier-antibody conjugate showing selective antibody-directed cytotoxicity in vitro.

Abstract: The preparation and properties of a drug-carrier-antibody preparation are reported. The antifolate chemotherapeutic agent methotrexate was covalently coupled to human serum albumin as a carrier. The carrier-drug preparation was then chemically linked to a monoclonal antibody, raised originally against a human osteogenic sarcoma cell line, 791T, in a manner permitting retention of antibody-binding activity. The cytotoxic properties of the conjugate were tested in vitro in comparison with carrier-methotrexate and free methotrexate against a panel of tumour cell lines containing both antigenically cross-reactive cell lines and cell lines having low antigenic cross-reactivity with the monoclonal antibody. The cytotoxicity tests demonstrated that coupling of methotrexate to carrier caused a loss of some drug activity but that coupling of the antibody to the carrier-drug preparation permitted full expression of drug cytotoxicity against antibody-reactive cell lines. It was further demonstrated that the conjugate was selective in its action and was preferentially cytotoxic towards antibody-reactive cell types. The cytotoxicity against antibody-reactive cell lines was shown by competitive inhibition by free antibody to be entirely dependent on antibody binding. A clonogenic assay showed that the conjugate was capable of killing greater than 99% of 791T target cells. These results indicate that a drug-carrier antibody conjugate can be synthesized which has all the in vitro properties theoretically necessary for a successful antibody-targeted cytotoxic agent.

Improved Therapeutic Benefits of Doxorubicin by Entrapment in Anionic

Abstract: When used as drug carriers, anionic liposomes can reduce the chronic cardiac toxicity and increase the antileukemic activity of doxorubicin (DXN; Adriamycin). Continuing investigations, reported here, have now established the therapeutic benefits of this mode of drug delivery. Liposome encapsulation caused a prolonged elevation in DXN plasma levels and a 2fold reduction in the exposure of cardiac tissue to the drug. This reduction, however, was not proportional to the substantial decrease in chronic heart toxicity observed in the earlier study. In vivo studies have demonstrated that the entrapped drug retains its full activity against Sarcoma 180 and significantly increases its action against Lewis lung carcinoma, as measured by reduced tumor volume. The increased antineoplastic activity was again not proportional to the increased association of drug with tumor tissue. The effect of liposome entrapment on the immune-suppressive activity of DXN was also examined to determine if factors other than the direct delivery of drug to tumor tissue might improve the therapeutic response. The suppression of the humoral immune response and peripheral leukocyte counts by free DXN was nearly abolished when the drug was administered in the liposome form. These experiments suggest that the improved therapeutic effect of encapsulation may be the outcome of three different mechanisms: (a) altered disposition into subcellular compartments, which reduces cardiotoxicity; (b) increased plasma drug exposure to tumor cells; and (c) significant reduction in the immune suppressive activity of DXN.

Dimethyl-β-cyclodextrin as parenteral drug carrier

Abstract: The following advantages are expected from the application of a soluble non-toxic inclusion-complexing drug carrier: (a) aqueous injectable solutions could be prepared from insoluble or poorly soluble drugs; (b) the stability of the dissolved drug could be improved; (c) by decelerating the elimination (by diffusion, circulation, metabolism) the duration of the biological effect could be prolonged; (d) by reducing the plasma, level of the active drug (=free, non-complexed drug) through complexation, the toxic effects could also be reduced; (e) in oral administration the bioavailability will be strongly enhanced.

Drug-carrier conjugates

Abstract: Biologically active drugs, e.g. catecholamine hormones, are coupled to carrier molecules, e.g. monodisperse peptides to produce conjugate molecules. The conjugate molecules retain biological activity, but the pharmacokinetic, pharmacodynamic and/or potency properties of the drug is modified. The drug is coupled to the carrier via a spacer moiety which not only serves to covalently link the drug to the carrier, but also insulates the biologically active portion of the drug, i.e., the pharmacophore, from degradation during the coupling process. The carrier preferably consists of a monodisperse peptide in which the sequence of amino acid residues is carefully preselected and controlled.

Polymers in Medicine : Biomedical and Pharmacological Applications

Abstract: Section I Polymeric Drugs and Drug Delivery Systems.- Characteristic Bilolgical Effects of Anionic Polymers.- Polymeric Antitumour Agents on a Molecular and on a Cellular Level?.- Utilization of Stabilized Forms of Polynucleotides.- Application of the Congener Approach to the Design and Synthesis of Peptide-Catecholamine Conjugates.- New Polymeric and Oligomeric Matrices as Drug Carriers.- Development of N-(2-Hydroxypropyl)Methacrylamide Copolymers as Carriers of Therapeutic Agents.- Biologically Active Compounds Immobilized on Cellulose Derivatives.- Preparation of Enzyme Polymers for Therapeutical Use! Preliminary "In Vivo" Study.- Synthesis and Characterization of Covalently Bound Polymer-Hormone Conjugates for the Controlled Release of Hormones.- Improved Drug Delivery to Target Specific Organs Using Liposomes as Coated with Polysaccharides.- Synthesis and Release of Contraceptive Steroids from Bioerodible Poly(Ortho Ester)s.- Press-Coated Systems for Drug Release Control.- Polymeric Ophthalmic Drug Delivery Systems! Preparation and Evaluation of Pilocarpine-Containing Inserts.- Basic Physical Parameters of Polymeric Matrices Influencing Drug Release.- Section II Polymers as Biomaterials.- Polymers in Medicine-An Overview.- Functional Polyesters and Polyamides for Medical Applications of Biodegradable Polymers.- Polyurethanes as Biomaterials - Assessment of Blood Compatibility.- Synthesis, Structural Study and Preliminary Hemocompatibility Tests of AB and ABA Block Copolymers with Polyvinyl and Polypeptide Blocks.- Interactions of Some Plasmatic Proteins with Anticoagulant Polystyrene Resins! Mechanism of Catalytic Activity towards the Thrombin-Antithrombin Reaction.- Characterization and Albumin Adsorption on Surface Oxidized Polyethylene Films.- Radiation Induced Modification of Polyetherurethane Tubes with HEMA and Acrylamide.- Improvement of the Biocompatibility of Polymers through Surface Modification.- Physical Characterization of Poly(2-Hydroxyethylmethacrylate) Gels: Effect of the Diluent Content on the Mechanical and Transport Properties.- Section III Medical and Surgical Applications of Polymers.- The Design of a Small Diameter Arterial Replacement.- The Development of Small Diameter Vascular Prostheses.- Testing Devices for the Evaluation of Prosthetic Heart Valves.- Development and Testing of a New Prosthetic Heart Valve.- Heparin-like Substances and Blood-Compatible Polymers Obtained from Chitin and Chitosan.- Advances in the Development of Extraction Resistant Flexible PVC Compounds.- Immobilization of Enzymes on Hollow Fibers Assembled after Chemical Modification.- Polymer Composite Materials in Orthopaedic Surgery.

Improved Drug Delivery to Target Specific Organs Using Liposomes as Coated with Polysaccharides

Abstract: An assembly of a cell wall-like structure on the outmost surface of liposomes has been constructed, which makes liposomes tough against chemical and physicochemical lyses of liposomal membranes caused by external stimuli. In accordance with this idea, we have prepared partly modified polysaccharides, (0-palmitoylpullulan (OPP) and (0-palmitoylamylopectin (OPA), and coated the outmost surface of egg phosphatidylcholine liposomes by them. The efficiency in coating liposomes with the artificial cell wall has been ascertained by four different methods: (1) isolation of polysaccharide-coated liposomes by gel-filtration, (2) reduced permeability for a water soluble material, carboxyfluorescein, encapsulated in the interior of liposomes, (3) increased resistance against the enzymatic lysis with phospholipase D for the coated liposomes, and (4) decreased probability in the enzymatic digestion with pullulanase of the polysaccharide strongly bound to the surface of liposomes. These results suggest a wider usage of the polysaccharide-coated liposomes as an improved drug carrier.

New polymeric and oligomeric matrices as drug carriers.

Abstract: The use of synthetic polymers in the pharmacological field is at present one of the newest and most exciting areas of polymer chemistry. In particular, the synthesis and the bioactivity of macromolecular drugs are receiving increasing attention by several groups1–38.

Liposomal Dosago Form Development—Some Practical Considerations

Abstract: Liposomes have attracted much attention in recent years as a potential drug carrier for parenteral use. Successful application of the liposomal drug delivery concept has been demonstrated in the treatment of experimental leishmaniasis with antimonial drugs in animal models. Development of this laboratory research concept into a viable product for clinical use is anticipated to pose numerous technological problems. Various approaches available to resolve some of the problems and to devise suitable formulations are considered. Finally, some of the experiences with the encapsulation of sodium stibogluconate (Pentostam) are briefly described.

Controlled Release of 5-Fluorouracil from Hydrophilic Ethylene-Vinyl Alcohol Copolymer Matrices

Abstract: Ethylene-vinyl alcohol (EVAl) 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 alcohol was investigated. The ethylene content of EVAl copolymer was varied from 32 to 60 mol%. An increase in ethylene comonomer content decreased the drug release from the polymer matrix. The release rate could be controlled by modifying the ethylene/vinyl alcohol ratios in the polymer matrices. Fabrication parameters such as drug content and surface area of matrices also affected the release kinetics. The release rates were shown to be proportional to release media temperature, but independent of the pH. Matrices composed of EVAl copolymer appeared to be stable on long-term storage with respect to release rate and could be useful vehicles for the controlled release of hydrophilic drugs.

Drug delivery systems

Abstract: Drugs have long been used to improve health and extend lives. The practice of drug delivery has changed dramatically in the past few decades and further changes are anticipated in the near future. Biomedical engineers have contributed substantially to our understanding of the physiological barriers to effi cient drug delivery, such as transport in the circulatory system and drug movement through cells and tissues; they have also contributed to the development of a number of new modes of drug delivery that have entered clinical practice.

Drug delivery systems.

Abstract: Drug delivery systems have an important role to play in the administration of drugs, vaccines, and diagnostic agents. Systems based on biodegradable polymers can be especially advantageous for use as implants that provide a slow, steady release of a pharmacological agent. Materials include poly-a-hydroxy acids, polyanhydrides, and polyphosphazenes. The products of biotechnology in the form of peptides and proteins are challenging compounds that are difficult to deliver. Novel methods of delivery include polymeric microspheres and microcapsules. Polymers can be used to deliver antigens in order to obtain improved responses after injection. Nanoparticles based on polymeric materials can be employed to deliver drugs to specific target sites, especially via the bloodstream or lymphatic system. Natural polymers also have an important role in drug delivery, for example chitosan is of special interest for its ability to interact with mucosal surfaces and to provide a bioadhesive effect that will retain drugs at target sites.