Showing papers on "Drug carrier published in 1985"
TL;DR: Degradation of these polyanhydrides was pH sensitive, being enhanced in high pH, and became more stable in acidic conditions, suggesting a release mechanism that was dominantly degradation controlled.
Abstract: Polyanhydrides based on a variety of aromatic and aliphatic dicarboxylic acids were developed as bioerodible carrier matrices for controlled delivery applications The high hydrolytic reactivity of the anhydride linkage provides an intrinsic advantage over other classes of bioerodible polymers in versatility and control of degradation rates For example, using the poly[bis(p-carboxyphenoxy) alkane anhydrides] as models, polymers with degradation rates in the range of 10(-1) to 10(-4) mg/h/cm2 were obtained by changing the alkane from a methyl to a hexyl group The polymers were characterized by infrared (IR), differential scanning calorimetry, gel permeation chromatography, and scanning electron microscopy (SEM) Near zero-order degradation kinetics were observed for the hydrophobic polyanhydrides over several months The drug release profile of the model drug p-nitroaniline followed closely that of the degradation of injection-molded poly[bis(p-carboxyphenoxy) propane anhydride] over a period of more than 8 months Close correlation of polymer degradation and drug release was also observed in other injection-molded samples (10% loading), suggesting a release mechanism that was dominantly degradation controlled Degradation of these polyanhydrides was pH sensitive, being enhanced in high pH, and became more stable in acidic conditions
527 citations
TL;DR: The kinetics of drug release from hydrogel matrices will be examined both experimentally and theoretically and special emphasis will be placed on the effect of local drug concentration on the swelling behavior ofhydrogel drug carriers.
353 citations
TL;DR: Negatively charged liposomes are endocytosed by the coated vesicle system and accumulate in acidic intracellular vesicles, which improve cytoplasmic delivery of membraneimpermeant macromolecules such as calcein and FITC dextran.
246 citations
Journal Article•
TL;DR: The general problem of targeted drug transport is critically reviewed and the most promising approach seems to be the use of a drug-containing microcontainer with the vector molecule immobilized on its outer surface.
Abstract: The general problem of targeted drug transport is critically reviewed and three principle components of targeted systems are discussed: the target, the vector molecule, and the carrier. Different systems of drug targeting are briefly described: local drug application, chemical modification of the drug molecule, physical targeting under the action of pH, temperature, or magnetic field. The idea of a vector molecule is discussed and different methods of vector molecule coupling with the drug are reviewed (direct coupling, coupling via spacer group or polymer molecule, etc.). It is shown that the most promising approach seems to be the use of a drug-containing microcontainer with the vector molecule immobilized on its outer surface. Different types of microcontainers are briefly described: microcapsules, cell hosts, and liposomes. The advantages of liposomes as drug containers are shown and the main problems of their use for drug targeting in vitro and in vivo conditions are discussed. One of the most important problems is the problem of vector molecule immobilization on liposome surfaces. The principle four different immobilization methods: adsorbtion, incorporation, covalent binding, and hydrophobic binding. Targeted liposome transport is described in model systems, cell cultures, and experimental animals. It is shown that targeted liposomes may release a drug via diffusion, lysis, or endocytosis by appropriate cells. The problems of targeted liposome technology and clinical application are analyzed.
118 citations
TL;DR: The various delivery systems that have recently been developed and those that are currently known to be under investigation are described in this paper, along with some observations regarding the future outlook of ophthalmic drug delivery systems.
Abstract: New ophthalmic drug delivery systems are curently 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, but also because of the potential of some delivery systems to reduce the side effects of the more potent drugs recently introduced or presently under investigation. Some ophthalmic delivery systems extend the duration of drug action by enhancement of corneal absorption; these systems include soluble gels and emulsions, hydrophilic ocular inserts, ion-pair associations, prodrugs, and liposomes. Since these systems enhance the “pulse entry” of the drug, they are limited to use with drugs whose dose-related side effects are not serious. Other delivery systems provide for a controlled release of drugs and therefore minimize the pulse entry with which side effects are associated. They can be based on any of several different mechanisms and include both erodible and nonerodible matrices. The various delivery systems that have recently been developed and those that are currently known to be under investigation are described in this paper, along with some observations regarding the future outlook of ophthalmic drug delivery systems.
112 citations
TL;DR: The present results suggest that the application of alkyl glycoside vesicles as drug carriers may be feasible and show longer lives on stage in an ampule at 20°C than phosphatidylcholine vesicle.
Abstract: It was observed that alkyl glycosides formed lamellar vesicles like phosphatidylcholine vesicles (liposomes), and the application of these vesicles as drug carriers was attempted. Various alkyl glycosides were synthesized and vesicles were prepared with these glycosides. The encapsulation capacity of the vesicles was examined in relation to alkyl chain length, sugar moiety, and lipid composition. The glucosides of myristyl, cetyl, and stearyl alcohols formed vesicles, but those of lauryl, decyl, and octyl alcohols did not. The vesicles of glucoside, galactoside, and mannoside showed fairly good encapsulation capacity but those of lactoside showed low capacity. An appropriate ratio of glycoside, cholesterol, and dicetylphosphate is an important factor for the formation of these vesicles, especially with regard to dicetylphosphate. The alkyl glycoside vesicles show longer lives on stage in an ampule at 20°C than phosphatidylcholine vesicles. The stability in plasma was also examined. The glycoside vesicles showed rapid release of about 40% of the aqueous contents, but after that, they showed outstanding stability for 48h in plasma at 37°C. On the other hand, phosphatidylcholine vesicles showed rapid release of only about 30%, but they disintegrated gradually and showed low encapsulation capacity (about 20%) after 48h. The present results suggest that the application of alkyl glycoside vesicles as drug carriers may be feasible.
97 citations
TL;DR: To date, Liposomes have been found to both promote and reduce ocular drug absorption, indicating that a definite need exists for further studies to evaluate the interplay of drug, liposomes, and the corneal surface in determining the effectiveness ofliposomes as vehicles for topically applied ophthalmic drugs.
81 citations
Journal Article•
TL;DR: Lipid microsphere preparations of corticosteroid, non-steroid anti-inflammatory drugs and prostaglandin E1 (PGE1) all showed more potent activity than the free drugs.
Abstract: SUMMARY Lipid microsphere preparations of corticosteroid, non-steroid anti-inflammatory drugs and prostaglandin E1 (PGE1) all showed more potent activity than the free drugs. Lipo-PGE1 in particular was significantly more active than free PGE1 at about one-tenth the dose of free PGE1. A large mass of data obtained in studies of liposomes suggest many applications for the lipid microsphere, which is considered to be a very promising carrier in drug delivery systems.
66 citations
Journal Article•
TL;DR: This review describes the progress which has been made during the last 10 to 15 years in the application of albumin microsphere as drug carriers to cancer chemotherapy and will cover a wide range of subjects including the preparation and physicochemical properties of microspheres containing antitumor agents, pharmacokinetics of themicrospheres in experimental animals, and the antitumors efficacy by intra-arterial use against human primary metastatic liver tumor.
Abstract: In order to improve the therapeutic index in cancer chemotherapy, it is necessary to deliver antitumor agents to target sites (tumor sites). One of the methods used to deliver those agents to target sites is to employ nontoxic and biodegradable drug carriers. Considerable efforts have been directed toward the development of drug carriers, i.e., DNA complexes, protein-drug conjugates, lactic/glycolic acid polymer, liposomes, emulsion, etc. Albumin microsphere is one of those drug carriers. This review describes the progress which has been made during the last 10 to 15 years in the application of albumin microspheres as drug carriers to cancer chemotherapy. It will cover a wide range of subjects including the preparation and physicochemical properties of microspheres containing antitumor agents, pharmacokinetics of the microspheres in experimental animals, and the antitumor efficacy by intra-arterial use against human primary metastatic liver tumor.
55 citations
Patent•
04 Jun 1985
TL;DR: In this article, a drug-containing carrier system for oral use in the form of an ultrafine suspension of lipid nanopellets consisting of lipids with surface-active agents, the particle diameter of which is 50-1,000 nanometers, preferably 80-800 nanometers.
Abstract: Drug-containing carrier system for oral use in the form of an ultrafine suspension of lipid nanopellets consisting of lipids with surface-active agents, the particle diameter of which is 50-1,000 nanometers, preferably 80-800 nanometers, the ratio of lipid to surfactant in the lipid nanopellets being 1: 0. 01 to 1: 2.2, preferably 1: 0.22 to 1: 1.2, in particular 1: 1 to 1: 0.22 and the lipid particles are present in the suspension in a concentration of 1-20% by weight . The lipid nanopellets can be loaded with pharmacologically active substances, so that an improved bioavailability is possible.
53 citations
TL;DR: This chapter discusses the dextran and inulin conjugates as drug carriers, which exhibit improved chemical and biological stability as well as changes in their pharmacokinetics by esterification and nonpolar linkage.
Abstract: Publisher Summary This chapter discusses the dextran and inulin conjugates as drug carriers. Dextran and inulin are pharmacologically inert, and as a result, the pharmacological properties of their conjugates are due to the linked drug. Many drugs conjugated to a polysaccharide carrier, such as dextran and inulin, exhibit improved chemical and biological stability as well as changes in their pharmacokinetics. By esterification of a drug with dextran and inulin, it is possible to produce a slow-release form of the drug. On the other hand, linking a drug or a biologically active substance by a nonpolar bond to dextran, it is possible to prolong its serum lifetime and pharmacobiological activity and to selectively reach the RES tissues, while the nonpolar bond to inulin gives the final conjugate a urinary tract tropism. In all these conjugates (by ester or nonpolar linkage), the polysaccharide carrier improves the chemical and chemicophysical stability of the linked drug.
TL;DR: Electric pulses in the range of 1 to 5 kV/cm and of durations 1 to 200 microseconds have been used to open up pores of limited size in various cell types and erythrocytes were shown to admit molecules as large as tetrasaccharides.
Abstract: Electric pulses in the range of 1 to 5 kV/cm and of durations 1 to 200 microseconds have been used to open up pores of limited size in various cell types. In the case of erythrocytes, these pores were shown to admit molecules as large as tetrasaccharides. Loading of clinically active drugs has also been attempted. Erythrocytes loaded with drugs can be resealed without loss of the hemoglobin content. With mouse erythrocytes, we have demonstrated the feasibility of using erythrocytes (not hemoglobin depleted ghosts) as drug carriers for prolonging the drug level in the circulation. Other possible applications of the method are also discussed.
Journal Article•
01 Jan 1985
TL;DR: Cell Targeting Techniques: Biochemical Methods for the Study of Receptor-Mediated Endocytosis and Entrapment in Red Cells and Ghosts and Liposome Carriers: Multiple Emulsions as Targetable Delivery Systems.
Abstract: Cell Targeting Techniques: Biochemical Methods for the Study of Receptor-Mediated Endocytosis. High-Efficiency Gene Transfer into Cells. Lectin-Specific Targeting of Lysosomal Enzymes to Reticuloendothelial Cells. Osmotic Lysis of Pinosomes. Liposome Carriers: Multiple Emulsions as Targetable Delivery Systems. High-Pressure Continuous-Flow System for Drug Entrapment in Liposomes. Temperature- and pH-Sensitive Liposomes for Drug Targeting. pH-Sensitive Immunoliposomes. Photolabile Liposomes as Carriers. Covalent Attachment of Proteins to Liposomes. Use of Avidin-Biotin Technology for Liposome Targeting. Complement-Dependent Phagocytosis of Liposomes by Macrophages. Interaction of Liposomes with Cells. Uptake of Liposome-Encapsulated Agents. Liposome-Mediated Macrophage Activities. Liposomes as Carriers for in Vivo Gene Transfer and Expression. Liposome Entrapment for Delivery of Genetic Material to Plant Protoplasts. Liposome-Encapsulated Hemoglobin as an Artificial Oxygen-Carrying System. Use of Liposomes as Agglutination-Enhancement Agents in Diagnostic Tests. Cellular Carriers: Erythrosomes: Erythrocyte Cytoskeletons Coated with Exogenous Phospholipid as an Encapsulating System. Hypotonic Hemolysis Methods for Entrapment of Agents in Resealed Erythrocytes. High-Efficiency Entrapment of Enzymes in Resealed Red Cell Ghosts by Dialysis. Dialysis Method for Entrapment of Proteins into Resealed Red Blood Cells. Large-Scale Entrapment of Drugs into Resealed Red Blood Cells Using a Continuous-Flow Dialysis System. Electric Modification of Membrane Permeability for Drug Loading into Living Cells. Drug-Induced Endocytosis and Entrapment in Red Cells and Ghosts. Preparation of White Resealable Erythrocyte Ghosts. Phospholipid Asymmetry of Loaded Red Cells. Red Cell-Mediated Microinjection. Magnetically Responsive Erythrocyte 'Ghosts'. Use of Platelets as Drug Carriers for the Treatment of Hematologic Diseases. Author Index. Subject Index.
TL;DR: The apparent lack of acute toxicity of these vesicles, as indicated by intravenous administration to outbred mice, further suggests that such photopolymerized liposomes may represent a unique and valuable carrier for the controlled delivery of certain types of therapeutic agents, especially by the oral route.
Abstract: Polymerized ammonium and phosphatidylcholine vesicles have been synthesized via poly(methacrylate) and poly(disulfide) formation. A functionalized polymeric liposome has also been synthesized and effectively conjugated with alpha chymotrypsin. Vesicles derived from 2 have been studied most extensively as potential carriers of drugs. The are extremely stable toward physical perturbation and exposure to organic solvents or detergents, and should be able to maintain their integrity and homogeneity during pharmaceutical manufacturing procedures, including lyophilization. The fact that they retain substantial quantities of lipophilic substances in the presence of detergent concentrations in excess of those found in the upper gastrointestinal tract suggests that they should be able to carry and selectively release lipophilic drugs in the lower reaches of the GI tract. Moreover, the apparent lack of acute toxicity of these vesicles, as indicated by intravenous administration to outbred mice, further suggests that such photopolymerized liposomes may represent a unique and valuable carrier for the controlled delivery of certain types of therapeutic agents, especially by the oral route.
TL;DR: A-ase encapsulated in FT liposomes was resistant to proteolysis by trypsin treatment and to leakage by osmotic shrinkage, and the use of an organic solvent or a detergent is unnecessary, sterilization can be carried out with a membrane filter and the preparation technique is simple.
Abstract: A new and simple technique for the preparation of liposomes, the freeze-thawing method (FT method), was developed and evaluated for encapsulation efficiency by using L-asparaginase (A-ase) as a model drug. The encapsulation percentage of A-ase in liposomes (EN%) was determined by three methods, i.e. the measurement of free and total activities of A-ase, the gel filtration method and the trypsin treatment method. A-ase was encapsulated in FT liposomes with a higher efficiency than in liposomes prepared by the hydration method (HY liposomes), although the shape, the particle size distribution and the appearance of multilamellar structure of FT and HY liposomes were similar to each other. A-ase encapsulated in FT liposomes was resistant to proteolysis by trypsin treatment and to leakage by osmotic shrinkage. The FT method has the following advantages over the HY method for the practical preparation of liposomes as drug carriers : the use of an organic solvent or a detergent is unnecessary, sterilization can be carried out with a membrane filter and the preparation technique is simple.
TL;DR: In this article, it was shown that drugs reputedly insoluble in water can be dissolved and temporarily trapped in a lipophilic microphase in a poly-[thio-1-(N,N-diethyl aminomethyl) ethylene] type with less than 20% quaternized repeating units.
Book•
01 Jul 1985
TL;DR: Liposomes as Drug Carriers to Liver Macrophages: Fundamental and Therapeutic Aspects and Alternate Delivery of Interferons.
Abstract: Mannose Binding Proteins in the Liver and Blood.- Cell Membrane Molecules on Neoplastic Cells: Their Role in Malignant Cell Transformation and Dissemination.- Tumor-Associated Glycolipid Markers: Possible Targets for Drug and Immunotoxin Delivery.- Interaction of Macromolecular Drugs with Receptors.- Endocytosis and Lysosomes: Recent Progress in Intracellular Traffic.- Peptides as Targets and Carriers.- Hepatic Functions in Health and Disease: Implications in Drug Carrier Use.- Targeting with Synthetic Polymers: A Realistic Goal.- Drug-Poly(lysine) Conjugates: Their Potential for Chemotherapy and for the Study of Endocytosis.- Targeting of Colloidal Carriers and the Role of Surface Properties.- Targetable Nanoparticles.- Polymers as Matrices for Drug Release.- Liposomes In-Vivo: A Relationship Between Stability and Clearance?.- Liposomes as Drug Carriers to Liver Macrophages: Fundamental and Therapeutic Aspects.- Alternate Delivery of Interferons.- Liposomes in Antimicrobial Therapy.- Design, Characterization and Antitumor Activity of Adriamycin-Containing Phospholipid Vesicles.- Particle Charge and Surface Hydrophobicity of Colloidal Drug Carriers.- Particle Size Analysis of Colloidal Systems by Photon Correlation Spectroscopy.- Stability of Liposomes on Storage.- Contributors.
TL;DR: Suppression of human α-foetoprotein-producing hepatocellular carcinoma growth in nude mice by an anti α- foetop protein antibody-daunorubicin conjugate with a poly-L-glutamic acid derivative as intermediate drug carrier is reported.
Abstract: Suppression of human α-foetoprotein-producing hepatocellular carcinoma growth in nude mice by an anti α-foetoprotein antibody-daunorubicin conjugate with a poly-L-glutamic acid derivative as intermediate drug carrier
TL;DR: The behaviour of liposomes during lyophilization processes, either in the presence or in the absence of sodium ioxitalamate and maltose, and differential scanning calorimetry (DSC) has been used to analyse the evolution ofliposome hydration.
TL;DR: The polar drug methotrexate has been coupled to the exterior protein of low density lipoprotein (LDL) particles using the reagent l-ethyl-3(3′-dimethylaminopropyl) carbodiimide HCl and the activity of the complex against L1210 murine leukaemia cells has been demonstrated in vitro.
Abstract: Low-density lipoprotein particles are potential drug carriers, but only lipophilic drug species partition into the core of the system. In this paper the polar drug methotrexate has been coupled to the exterior protein of low density lipoprotein (LDL) particles using the reagent l-ethyl-3(3′-dimethylaminopropyl) carbodiimide HCl. The coupled system was sized by photon correlation spectroscopy and the in vitro activity of the complex determined against L1210 cells maintained in medium supplemented with fetal calf serum. The reaction between methotrexate and low density lipoprotein is variable but quantifiable, about ten drug molecules being attached to each LDL particle, resulting in an increase in the radius and polydispersity of the particles. The activity of the complex against L1210 murine leukaemia cells has been demonstrated in vitro, but it is 30 times less active than free drug.
Journal Article•
TL;DR: It is indicated that LMs could be used as a novel drug carrier, similarly to liposomes, in a drug delivery system specific for areas of inflammation and reticuloendothelial systems.
Abstract: The tissue distribution of lipid microspheres (LMs), drug carriers for targeting therapy of anti-inflammatory drugs, was morphologically studied by electron microscope. In areas of inflammation in rats and mice, LMs were taken up by macrophages and accumulated around endothelial cells of blood vessels, and were observed to penetrate to the outer layer of blood vessels. LMs were also observed in reticuloendothelial cells such as Kupffer cells and splenic macrophages. Furthermore, the uptake of LMs by polymorphonucleocytes (PMNs) in areas of inflammation was enhanced 2-3 fold when LMs were coated with homogeneous IgG. These findings are in agreement with the tissue distribution results previously reported by the authors in studies using radioisotope-labelled LMs. The present and previous reports indicate that LMs could be used as a novel drug carrier, similarly to liposomes, in a drug delivery system specific for areas of inflammation and reticuloendothelial systems.
Book•
13 Aug 1985
TL;DR: This work discusses pharmacodynamic and Pharmacokinetic Factors Influencing Directed Drug Delivery, Applications of Miniature Electrodes to Biomedical Studies, and Approaches to improve Specificity and Sensitivity in Chromatography.
Abstract: A. Pharmacodynamic and Pharmacokinetic Factors Influencing Directed Drug Delivery.- Pharmaceutics and the Evolving Technology of Drug Delivery-A Perspective.- Pharmacodynamic Considerations in the Development of New Drug Delivery Concepts.- Molecular Mechanisms of Drug Action and Pharmacokinetic-Pharmacodynamic Models.- The Therapeutic System: Therapeutic Implications of Rate-Controlled Drug Delivery.- B. Physiological and Biochemical Factors Influencing Directed Drug Delivery.- Gastrointestinal Barrier to Oral Drug Delivery.- Strategies for Drug Delivery Through the Blood-Brain Barrier.- The Dermal Barrier to Local and Systemic Drug Delivery.- C. Physical-Chemical Approaches to Directed Drug Delivery.- A Physical Approach to Drug Delivery.- Microparticulate Drug Carriers.- Biodegradable Poly(ortho Esters) as Drug Delivery Forms.- Macromolecules as Drug Delivery Systems.- D. Biological-Chemical Approaches to Directed Drug Delivery.- Monoclonal Antibody Mediated Drug Delivery and Antibody Toxin Conjugates.- Drug Delivery Via Cell-Surface Receptors.- Prodrugs: A Chemical Approach to Targeted Drug Delivery.- New Drug Delivery Systems: Physico-Chemical Considerations.- E. Analytical Aspects of Drug Delivery.- Analytical Aspects of Drug Delivery: An Important and Often Overlooked Problem.- Applications of Miniature Electrodes to Biomedical Studies.- The Use of Scintigraphic Methods for the Evaluation of Novel Delivery Systems.- Approaches to Improve Specificity and Sensitivity in Chromatography.
Book•
01 Jan 1985
TL;DR: Oral Drug Bioavailability: Variations, Limitations, and Control Theraputic Systems: The ALZA Concept Automatic, Feedback Controlled, Drug Delivery Devices Percutaneous Absorption Bioavailibility Properties of Osmotically Controlled Drug Delivery Systems
Abstract: Oral Drug Bioavailability: Variations, Limitations, and Control Theraputic Systems: The ALZA Concept Automatic, Feedback Controlled, Drug Delivery Devices Percutaneous Absorption Bioavailibility Properties of Osmotically Controlled Drug Delivery Systems The Control of Drug Bioavailibility from Ophthalmic Dosage Forms Bioavailibility of Macromolecular Drugs and Its Control Molecular Entrapment and Release Properties of Drugs by Cyclodextrins Index.
Journal Article•
TL;DR: Experimental and clinical application of Lip-ADM was started for patients with hepatic metastasis of gastrointestinal cancer by selective hepatic arterial infusion and antigen-specific acceleration of in vitro and in vivo anti-tumor effects was observed.
Abstract: To improve the targeting effect in cancer chemotherapy, liposomes containing Adriamycin (Lip-ADM) and monoclonal antibody-conjugated Lip-ADM (Lip-ADM = Ab) were prepared and examined experimentally and clinically. The liposomes used as biodegradable drug carriers, were prepared from a lipid mixture of egg yolk phosphatidylcholine, cholesterol and dipalmitoyl phosphatidic acid and Adriamycin (ADM) solution was added to prepare multilamellar vesicles (MLV). Small unilamellar vesicles (SUV) were prepared from MLV by sonication and monoclonal antibodies were conjugated to SUV by the SPDP method. Experimentally, antigen-specific acceleration of in vitro and in vivo anti-tumor effects was observed. As a high tissue distribution of Lip-ADM in the liver was observed and as sinusoidal capillaries, which are found in the liver, were expected to allow penetration of liposomes through the relatively large gaps in the endothelium into the underlying organ parenchymal cells, clinical application of Lip-ADM was started for patients with hepatic metastasis of gastrointestinal cancer by selective hepatic arterial infusion. Ten patients were treated by Lip-ADM which was administered at 8-30 mg/body cumulatively. No serious adverse reaction was observed except slight fever and leukocytopenia. The preliminary evaluation of anti-tumor effects on hepatic metastasis was LPR, 1MR, 6NC and 1PD. Repeat administrations of Lip-ADM or Lip-ADM = Ab using a retained infusion catheter and silicone reservoir were started in order to improve the more accelerated clinical effects.
Journal Article•
01 Jan 1985
TL;DR: In this paper, the use of monomeric and linear polymeric derivatives of cis-dichlorodiamine platinum II in medical applications emphasizing cancer chemotherapy is described, and the major area lacking definitive results concerns the site specific delivery determined by the use a controlled drug release, natural polymers, suitably tailored synthetic polymers and polymer length and shape.
Abstract: While the synthesis of biologically active compounds is widespread, the major area lacking definitive results concerns the site specific delivery determined by the use of controlled drug release, natural polymers, suitably tailored synthetic polymers and polymer length and shape. The previous paper describes the use of monomeric and linear polymeric derivatives of cis-dichlorodiamine platinum II in medical applications emphasizing cancer chemotherapy.