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At least 145 records · Page 8Linked to original sources
PubMed1987

Improved delivery through biological membranes. XXX. Synthesis and biological aspects of a 1,4-dihydropyridine based chemical delivery system for brain-sustained delivery of hydroxy CCNU.

A redox chemical delivery system based on the NADH in equilibrium NAD+ model was applied to an active metabolite (D) of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), i.e. CCNU-OH. The 1,4-dihydrotrigonelline ester of CCNU-OH, N-(2-chloro ethyl)-N'-[trans-4-(1,4-dihydro-1-methyl-3-pyridinecarbonyloxy)cyc lohexyl]- N-nitrosourea (D-CDS) was prepared by a direct hydride transfer reaction of the corresponding pyridinium precursor (D-Q+) with a highly reactive 1-benzyl-1,2-dihydroisonicotinamide. The in vitro kinetics in biological fluids indicated facile oxidative conversion of D-CDS to D-Q+. An in vivo study showed that one intravenous injection to rats of D-CDS resulted in rapid brain accumulation of D-Q+, followed by a sustained release of CCNU-OH, while D-Q+ was rapidly eliminated from systemic circulation. The ratio of brain/blood concentration of D-Q+ was found to increase progressively with time. At an equimolar dose of CCNU-OH, the ratio of brain/blood concentration for CCNU-OH was found to be close to unity.

Animals↗
PubMed1990

Drug delivery systems: 3A. Role of polymers in drug delivery.

At present, polymers represent a class of ubiquitous materials. They are being used for a multitude of purposes and the almost inexhaustible varieties of molecular architecture that macromolecular materials can possess provides the possibility for a myriad of applications. Because of the increased interest being shown in the macromolecules by the pharmaceutical industry for the fabrication of drug delivery systems, numerous polymers have been synthesized and successfully used in drug delivery devices. The necessary conditions for developing the concept of pharmaceutically applicable polymers depend upon delineating a detailed knowledge of the relationship between the structure and properties of polymer networks. A number of polymers have been studied systematically from this point of view and there is every indication that the systems described have the potential to become clinically valuable and therefore marketable drug delivery systems. The potential of these promising polymers is still far from being exhausted and there is a strong possibility that many important developments will be forthcoming in this field in the future. In the current review article, polymers for controlled release have been divided into four major categories: diffusion-controlled systems; chemically controlled systems; solvent-activated systems; and magnetically controlled systems. Polymers as drug carriers also have been divided into various subgroups: soluble, biodegradable, mucoadhesive and other polymeric systems. The latter group includes polymers containing pendant bioactive substituents, matrix systems, heparin-releasing polymers, ionic polymers, oligomers and miscellaneous. At an introductory and fundamental level, an overview of these polymers and the materials science for the design of drug delivery systems will be discussed.

Animals↗
PubMed2005

Immunity in response to particulate antigen-delivery systems.

Adjuvants and antigen-delivery systems are essential in inducing and modifying immune responses, and despite the variety of materials available for such use, mechanisms by which they support immunity appear to be little known. A common denominator for most antigen-delivery systems is their particulate nature. Together with a certain depot effect, it is the particulate nature that primarily decides whether the antigen-delivery system will be successful in inducing an immune response. If this first requirement is fulfilled, the chemical composition of the vaccine decides which type of immune response will develop, e.g. which isotype of antibodies the B cells will produce, and which cytokines the T cells will secrete, and can be controlled by combining the antigen with immunomodulatory or co-stimulatory molecules. It is our goal to provide an overview of the cellular and molecular factors involved in the induction of immunity and how such factors may influence the potency of an adjuvant or a vaccine. Such factors should then be implemented in the design of new vaccines or in tuning the properties of existing vaccines in order to reach the properties that are necessary for successful vaccination.

Adjuvants, Immunologic↗
PubMed2004

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

Administration, Oral↗
PubMed2000

Vaccine delivery: lipid-based delivery systems.

Needle-free delivery of vaccines should not only increase compliance, but should also prove to be a safer and less traumatic method of vaccine delivery. One of the potential ways to achieve needle-free delivery is with the use of lipid-based delivery systems. To demonstrate the utility of these systems, we have shown them to be effective with proteins produced by recombinant DNA technology, plasmid-based vaccines, as well as conventional vaccines. Furthermore, these lipid-based delivery systems were shown to be effective in inducing mucosal immunity if delivered to mucosal surfaces or systemic immunity if different transdermally. These approaches have the potential to revolutionize vaccine delivery in humans and animals.

Humans↗
PubMed2006

Systemic delivery of drugs to humans via inhalation.

Unwanted systemic absorption of drugs delivered for the local treatment of respiratory disease is well documented. Methods to minimize this now exist, especially for reduction of oropharyngeal deposition. While small molecules appear to be absorbed also from the airways, it is the alveolated regions that provide a large absorptive surface. Lung has been used as a portal for systemic delivery of substances such as anesthetics, nicotine and a number of illicit drugs. Much research has lead to the solutions of the fundamental technical hurdles of practicable delivery of systemic therapeutic drugs in milligram quantities to the lung efficiently and reproducibly. Commercial manufacturing processes exist for production of delivery systems suitable for this purpose. Generally, the deposition of small molecules in the "deep lung" leads to high absorption rates, making the inhalation delivery attractive for drugs with intended rapid onset of action. Many therapeutics, especially peptides and proteins, that cannot be delivered systemically non-invasively, are absorbed with various degrees of systemic bioavailability via inhalation. The critical factor for efficient and reproducible systemic delivery is lung deposition which depends on the properties of drug particles (size, shape, density, hygroscopicity, velocity, charge) and the state of the respiratory system (including the individual's anatomy, age, sex, disease, lung volume). While concerns exist about the potential adverse reactions of the immune system to therapeutic proteins and peptides delivered to and through the lung, there is not much data on the immune response or its link to any safety issues with inhaled biologics. Desirable systemic immune effects have been demonstrated by cytokine delivery to the lung.

Absorption↗
PubMed2004

The use of high-fidelity human patient simulation and the introduction of new anesthesia delivery systems.

New anesthesia delivery systems are becoming increasingly complex. Although equipment is involved in a large proportion of intraoperative anesthesia problems (most also involving human error), the current methods of introducing new equipment into clinical practice have not been well studied. We designed a randomized, controlled, prospective study to investigate an alternative method of introducing new anesthesia equipment. Fifteen anesthesiology trainees were randomized to either the standard introduction to a Drager Fabius GS anesthesia delivery machine plus simulated clinical use of the new machine in a high-fidelity human patient simulator (HPS) (Group 1) or to the standard introduction alone (Group 2). We used a questionnaire to seek their opinion on the new equipment, and responses showed that both groups were comparable in their reported confidence to use the new equipment safely. All trainees were then tested in two simulated anesthetic crises with the new machine. Performance was analyzed in terms of time to resolve the emergency, by using analysis of videos by an independent rater. Group 1 resolved both crises significantly faster. HPS allowed us to detect design features that were common sources of error.

Anesthesia↗
PubMed1997

Organization design of integrated delivery systems.

Healthcare integrated delivery systems (IDSs) evolve through four observed stages of development, with each successive stage having greater levels of interdependence among facilities and between facilities and physicians. The cottage industry stage is characterized by competition among hospitals and little interdependence. Healthcare organizations in the next stage, horizontally integrated systems, have pooled interdependencies, and in the third stage, vertically integrated systems, have predominately sequential interdependence with reciprocal interdependence between physicians and hospitals. In the fourth stage, community healthcare, community systems have reciprocal interdependence among their facilities and other organizations providing services along the continuum of care. This reciprocal interdependence is characteristic of the level of integration that must be addressed for system effectiveness. Greater levels of interdependence require stronger organizational integrating mechanisms and processes. "Integrative management" or "service-line management" is one vehicle for providing this integration. Although few empirical studies are available, this article relates the available empirical and conceptual literature to analyze the interdependencies at each level of IDS development, as well as the organizational design characteristics to address those interdependencies. It then examines the organization of the Veterans Health Administration (VHA) in terms of the four stages of IDS evolution, and suggests organization designs to address VHA's increased needs for integration.

Community Networks↗
PubMed1994

Reforming the health care delivery system.

The health care delivery system is evolving rapidly. There have been changes in the way health care is financed, the types of treatments available, the sites of care, and the physician patient relationship. These changes have resulted primarily from reactions to health care cost inflation. Health care reform is likely to accelerate some of these changes. The threat/promise of health care reform has already accelerated the consolidation of the health care services market. Health care reform is likely to reduce the number of insurers, increase the number of Americans in managed health care plans, increase the number of physicians in group practice, change provider income, and in general make the health care delivery system more concentrated and vertically integrated.

Cost Control↗
PubMed1998

Process improvement program evolves into compliance program at an integrated delivery system.

An integrated delivery system discovered questionable practices when it undertook a process-improvement initiative for its revenue-to-cash cycle. These discoveries served as a wake-up call to the organization that it needed to develop a comprehensive corporate compliance program. The organization engaged legal counsel to help it establish such a program. A corporate compliance officer was hired, and a compliance committee was set up. They worked with counsel to develop the structure and substance of the program and establish a corporate code of conduct that became a part of the organization's policies and procedures. Teams were formed in various areas of the organization to review compliance-related activities and suggest improvements. Clinical and nonclinical staff attended mandatory educational sessions about the program. By approaching compliance systematically, the organization has put itself in an excellent position to avoid fraudulent and abusive activities- and the government scrutiny they invite.

Accounts Payable and Receivable↗
PubMed1993

Simulation and optimisation of a self-regulating insulin delivery system.

The delivery of insulin is an integral part of the treatment of diabetes. It has been shown that an implantable polymeric system which releases insulin in response to blood glucose levels is feasible. This work aims to guide further experimental development of this system by constructing a mathematical model of the polymer matrix and analysing its functional characteristics by computer simulations. The system is an implantable polymer containing tri-lysyl insulin and the enzyme glucose-oxidase, and the feedback mechanism is based on the enzymatic reaction between glucose and glucose-oxidase. Acid produced from this reaction reduces the pH in the microenvironment of the polymer, which causes an increase in insulin solubility and release rate. The model was developed on the basis of the physical and chemical properties of the system, which were chosen in the light of direct observations with scanning electron microscopy combined with experimental measurements and reported values, and was validated by comparison with experimental results and by verification of some of its assumptions. Optimisation was undertaken by simulating the effect of different parameters of the system on its performance. Enzyme concentration, pore length, particle size and insulin loading were found to have surprisingly little effect. However, performance was significantly improved by using a hypothetical insulin molecule with a different solubility characteristic. The study can therefore provide a rational basis for the experimental development of a polymer-based artificial pancreas.

Algorithms↗
PubMed1999

Crystallization of beta-estradiol in an acrylic transdermal drug delivery system.

Transdermal drug delivery systems are pharmaceutical products that can deliver controlled doses of drugs from polymeric patches applied on the human skin. The long-term stability of these patches is a critical issue relative to their performance in delivering drugs at a constant rate. Where a drug has been dissolved in the polymeric adhesive patch, crystallization has been reported in several systems. This study uses a variety of characterization tools to determine the physical and chemical nature of the precipitates formed in situ in estradiol patches. Optical microscopy revealed that crystals were formed in a single layer inside the adhesive matrix and that there were two distinctly different morphologies: needle-like crystals and aggregates around the needles. From IR measurements it was evident that estradiol probably was present in more than one crystal form in these patches. Raman microscopy showed that the needle-like crystals contain the adhesive component and the aggregates some modified crystal form of estradiol, indicating that in addition to the drug, the polymeric adhesive also crystallizes during storage.

Acrylic Resins↗
PubMed1990

Adverse dermatologic reactions to transdermal drug delivery systems.

Transdermal drug delivery systems are marketed in the United States for four different drugs, and others are in various stages of development. Cutaneous side effects occur frequently with these systems and sometimes necessitate discontinuation of therapy. This article will review these adverse reactions.

Administration, Cutaneous↗
PubMed1993

The effect of dihydronicotinate N-substitution on the brain-targeting efficacy of a zidovudine chemical delivery system.

Enhanced brain delivery of zidovudine (AZT) has been demonstrated using a redox-based chemical delivery system (CDS). Optimization of the prototype AZT-CDS (5'-[(1-methyl-1,4-dihydropyridin-3-yl)carbonyl]-3'-azido-3'-deoxy thymidine ) was investigated by manipulation of the N-methyl group present on the dihydronicotinate portion of the molecule and examining the release of AZT in vivo in a rat model. Of the five compounds examined, all produced higher brain levels and lower blood levels of AZT than did AZT itself. In comparing the novel AZT-CDS analogues to the N-methyl benchmark, the N-propyl system proved to be the most efficient of the compounds tested.

Animals↗
PubMed1979

Placebo granules as cores for timed release drug delivery systems.

A drug delivery system is proposed constituted of spherical placebo granules as cores with polymeric surface films containing drug. This timed release dosage form has been prepared by means of a fluidized bed coating technique using ethyl cellulose as the polymeric film and caffeine and salicylic acid as model drugs. The release of the drugs from the dosage form (a) at different drug concentrations and (b) into solutions of different pH showed that drug release was linearly related to the square root of time. Good agreement was found between the theoretical release rate of caffeine, calculated according to Higuchi's equation for a homogenous matrix using membrane permeation parameters measured on linear films, and the experimental results in the case of low drug concentrations. Deviation of the release rate from the homogenous model at high drug concentrations could be explained by crystallization of the drug from the film.

Caffeine↗
PubMedDate not supplied

A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 1. Synthesis and characterization.

Nonviral gene delivery systems are amenable to forming colloidal particles with a wide range of physicochemical properties that include size, surface charge, and density and type of ligand presented. However, it is not known how to best design these particles without having a set of physicochemical design constraints that have been optimized for the intended gene delivery application. Here, a nanoparticle-based model delivery system is developed that can mimic the surface properties of nonviral gene delivery particles, and this model system is used to define design constraints that should be applied to next generation gene delivery particles. As a test case, a well-defined nanoparticle-based system is developed to guide the rational design of gene delivery to hepatocytes in the liver. The synthetic scheme utilizes monodisperse polystyrene particles and provides for variation of mean particle size and particle size distribution through variation in reaction conditions. The nanoparticles are PEGylated to provide stability in serum and also incorporate targeting ligands, e.g., galactose, at tunable densities. Four nanoparticles are synthesized from uniformly sized polystyrene beads specifically for the purpose of identifying design constraints to guide next generation gene delivery to the liver. These four nanoparticles are Gal-50 and Gal-140, that are galactosylated 50 and 140 nm nanoparticles, and MeO-50 and MeO-140, that are methoxy-terminated 50 and 140 nm nanoparticles. All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density. The availability of galactose ligands to receptor binding is demonstrated here by agglutination with RCA120.

Animals↗
PubMed1998

Charting the information technology direction for an integrated delivery system.

Automating the healthcare integrated delivery system requires a special set of skills, talent, and communication that goes beyond the capability of the i.t. manager alone. Bringing together all elements of the integrated delivery system and forming a well-integrated information environment will require a level of teamwork rarely seen in any industry. Today's IT manager is like an orchestra conductor. He or she should look ahead in the musical composition, manage the tempo, and bring all the sounds of the eclectic set of instruments together in harmony and achievement of the melody. Following the key success factor outlined here may not guarantee success in automating the integrated delivery system, but following them should keep the process harmonious.

Computer Communication Networks↗