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At least 55 records · Page 3Linked to original sources
PubMed1978

Progestin permeation through polymer membranes II: diffusion studies on hydrogel membranes.

The potential use of hydrogels in controlled-release drug delivery systems for contraceptive steroids was investigated. The permeabilities, diffusion coefficients, and partition coefficients for progesterone were determined for hydrogels made from hydroxyethyl methacrylate containing varying amounts of ethylene glycol dimethacrylate and tetraethylene glycol dimethacrylate. In addition, copolymers of hydroxyethyl methacrylate with methoxyethyl methacrylate and methoxyethoxyethyl methacrylate were investigated. The results were interpreted in terms of the mechanisms of permeation of progesterone through the hydrogels. This study showed that progesterone permeated these membranes primarily through loose pores in the hydrogel network except at high concentrations of the cross-linker, ethylene glycol dimethacrylate, where dissolution and diffusion of the progesterone in the polymer network was the dominant mechanism.

Acrylic Resins↗
PubMed1979

Preparation and evaluation of microencapsulated ion-exchange resin beads.

Ion-exchange resin beads in the benzoate form were coated by several microencapsulation techniques to alter and improve characteristics, especially the control of drug release, of this type of drug delivery system. The most successful techniques included polymer-polymer interaction, temperature change, and nonsolvent addition. The microencapsulated beads then were studied with respect to the release rate of the organic anion to determine the effects of microencapsulation. The release rate of the organic anion could be controlled over a wide range, depending on the encapsulating material characteristics. Factors affecting the extent and rate of release as result of microencapsulation are discussed.

Benzoates↗
PubMed2026

Multidimensional Protein Corona Analysis Toward Predictive Nano-Bio Interface Design.

Nanoparticles entering biological fluids are rapidly coated by proteins and other biomolecules, converting their synthetic surfaces into biologically active nano-bio interfaces. These coronas regulate colloidal stability, immune recognition, cellular uptake, biodistribution, pharmacokinetics, cargo delivery, and toxicity. Yet a protein list obtained by mass spectrometry captures only part of this interface. Corona identity and function are also shaped by protein organization, binding stability, exchange dynamics, conformational changes, and molecular accessibility. Here, we discuss recent progress in protein corona isolation and analysis from a question-oriented analytical perspective, with emphasis on how centrifugation, magnetic recovery, affinity- or chemistry-enabled capture, chromatography, filtration, and field-flow fractionation (FFF) influence the fidelity, integrity, and comparability of recovered coronas. We then examine how proteomic profiling can be integrated with binding measurements, interfacial structural analysis and functional validation to distinguish descriptive corona signatures from biologically meaningful mechanisms. We further consider how biofluid composition, disease state, tissue interfaces and cellular environments remodel corona identity, presentation, and bioactivity. Finally, we argue that standardized reporting, computational modeling, and AI-enabled approaches are essential for converting protein corona datasets into reproducible and predictive knowledge that can guide the design of drug delivery systems and precision nanomedicines.

Protein Corona↗
PubMed2017

Drug target ontology to classify and integrate drug discovery data.

BACKGROUND: One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome. RESULTS: As part of that effort, we have developed a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. CONCLUSIONS: DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource.

Biological Ontologies↗
PubMed2026

HIV-Associated Lymphomas: Updates from Pathogenesis to Treatment Strategies.

HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lymphomas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and oncogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemotherapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19- CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy trials. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticlebased drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision medicine that integrates tumor genomics and viral dynamics.

Humans↗
PubMed1978

Medication delivery time requirements in centralized and decentralized unit dose drug distribution systems.

Medication delivery time requirements in centralized and decentralized unit dose drug distribution systems were compared. Four stages in the receipt of medication orders and the delivery of doses were identified, and the time required to perform each stage was recorded by pharmacist observers for seven days in each system. In the centralized system, it required 138--220 minutes to deliver doses after orders were ready to be collected at the nursing station, with the time varying according to order type. The same cycle required 1--40 minutes in the decentralized system. Delays in medication delivery were shorter in the decentralized system.

Georgia↗
PubMed2026

Engineering strategies and translational progress in targeted nanoparticle drug delivery.

INTRODUCTION: Nanoparticle-based drug delivery has emerged as a transformative approach in modern therapeutics, offering improved targeting efficiency, enhanced pharmacokinetics, and reduced systemic toxicity compared to conventional drug delivery systems. AREAS COVERED: This review comprehensively examines major nanocarrier platforms, including lipid-based, polymeric, inorganic, and hybrid systems, with emphasis on their structural design and functional properties. It further explores current advancements in targeting strategies, including passive targeting via the enhanced permeability and retention (EPR) effect and active targeting through ligand-receptor interactions involving antibodies, peptides, aptamers, and small molecules. Key biological and technological barriers to clinical translation are also discussed, such as tumor heterogeneity, abnormal vasculature, dense extracellular matrix, immune clearance, and limited cellular uptake. Additionally, emerging stimuli-responsive systems, including pH-, redox-, and enzyme-sensitive nanocarriers, are highlighted for their role in controlled and site-specific drug release. EXPERT OPINION/COMMENTARY: Despite significant progress, the clinical translation of nanomedicine remains constrained by biological complexities and scalability challenges. Future advancements integrating biomimetic strategies, multifunctional design, and artificial intelligence-driven modeling are expected to enhance targeting precision, biocompatibility, and translational success.

Humans↗
PubMed2021

GCN2 kinase activation by ATP-competitive kinase inhibitors.

Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.

Adenosine Triphosphate↗
PubMed1978

Hospital pharmacy in Australia.

Hospital pharmacy practice in Australia is reviewed. Topics covered include pharmaceutical education, drug distribution, purchasing of pharmaceuticals, and hospital pharmacy staffing and services. Australia has a national health insurance system which directly affects both community and hospital pharmacy practice. While traditionally Australian hospital pharmacy practice has followed the British system of drug delivery, practitioners have tried to introduce innovations such as intravenous admixture services, unit dose drug distribution systems and drug information services. The limitations imposed by restricted governmental funds have inhibited the introduction of innovations. The Society of Hospital Pharmacists of Australia offers a continuing education correspondence course which leads to the granting of a Fellowship in Hospital Pharmacy.

Australia↗
PubMed1975

Elementary osmotic pump.

The elementary osmotic pump is a new delivery system for drugs or other active agents; it delivers the agent by an osmotic process at a controlled rate. Control resides in the: (a) water permeation characteristics of a semipermeable membrane surrounding the formulated agent, and (b) osmotic properties of the formulation. In its simplest embodiment, the system is constructed by coating an osmotically activie solid agent with the rate-controlling, semipermeable membrane. This membrane contains an orifice of critical size through which solubilized agent is dispensed. The system can contain the agent in solid form at loading higher than 90% of the total volume, and the agent can be delivered at rates several orders of magnitude higher than can be achieved by solution diffusion through polymeric membranes. The delivery rate, the fraction of total content delivered at zero order, and the system's delivery portal size have been calculated for delivery of a single compound. Experimental work verified the theory. The release rate from the system was found to be independent of outside agitation when the system is not deformed by shaking action, the pH of the environment, and delivery portal size for sizes within a specified range. The delivery rate from this system in vitro and in the GI tract of dogs was found to be equal.

Animals↗
PubMed1977

Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH.

A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate.

Absorption↗
PubMed1977

Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids.

The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study.

Absorption↗
PubMed2026

Food-derived extracellular vesicles as delivery platforms for medicine-food homology components in metabolic syndrome.

Diet-induced obesity and associated metabolic syndromes have become major global public health challenge, highlighting the urgent need for safe and effective strategies. Recently, food-derived extracellular vesicles (FDEVs) have garnered increasing attention as natural nanocarriers due to their excellent biocompatibility and specific targeted delivery capabilities. FDEVs can efficiently deliver medicine-food homology components (MFHCs) to precisely regulate lipid metabolism, inflammatory responses, and insulin sensitivity, thereby improving obesity and its metabolic abnormalities. This systematic review summarizes recent advances in the use of FDEVs as delivery vehicles for MFHCs to suppress diet-induced obesity and metabolic syndrome, with a particular focus on the underlying molecular mechanisms, including signaling pathway regulation and cellular metabolic remodeling. In addition, the clinical translational potential and industrial application prospects of FDEVs are evaluated, and key challenges related to preparation techniques, safety assessment, and large-scale production are discussed. By integrating current evidence, this review aims to provide theoretical framework and future perspectives for the development of FDEVs as a novel targeted delivery platform and treatment of metabolic diseases.

Extracellular Vesicles↗
PubMed2024

Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites.

Brain metastasis of advanced breast cancer often results in deleterious consequences. Metastases to the brain lead to significant challenges in treatment options, as the blood-brain barrier (BBB) prevents conventional therapy. Thus, we hypothesized that creation of a nanoparticle (NP) that distributes to both primary tumor site and across the BBB for secondary brain tumor can be extremely beneficial. Here, we report a simple targeting strategy to attack both the primary breast and secondary brain tumors utilizing a single NP platform. The nature of these mitochondrion-targeted, BBB-penetrating NPs allow for simultaneous targeting and drug delivery to the hyperpolarized mitochondrial membrane of the extracranial primary tumor site in addition to tumors at the brain. By utilizing a combination of such dual anatomical distributing NPs loaded with therapeutics, we demonstrate a proof-of-concept idea to combat the increased metabolic plasticity of brain metastases by lowering two major energy sources, oxidative phosphorylation (OXPHOS) and glycolysis. By utilizing complementary studies and genomic analyses, we demonstrate the utility of a chemotherapeutic prodrug to decrease OXPHOS and glycolysis by pairing with a NP loaded with pyruvate dehydrogenase kinase 1 inhibitor. Decreasing glycolysis aims to combat the metabolic flexibility of both primary and secondary tumors for therapeutic outcome. We also address the in vivo safety parameters by addressing peripheral neuropathy and neurobehavior outcomes. Our results also demonstrate that this combination therapeutic approach utilizes mitochondrial genome targeting strategy to overcome DNA repair-based chemoresistance mechanisms.

Brain Neoplasms↗
PubMed1977

Physicochemical considerations and pharmacokinetic behavior in delivery of drugs to the central nervous system.

The blood-brain barrier is not as rigid or as formidable as once believed. When experimental tumors of the central nervous system (CNS) and tumors of non-CNS origin are implanted intracerebrally (ic), they will grow and kill the host. It was once thought that only a few select agents, such as the nitrosoureas, were capable of crossing the blood-brain barrier and inhibiting tumor growth. There are now considerable data available which indicate that a variety of agents such as cytosine arabinoside, methotrexate, 6-mercaptopurine, 5-fluorouracil, procarbazine, melphalan, and cyclophosphamide, as well as the nitrosoureas, may significantly influence the growth rate of experimentally implanted ic tumors. A number of physicochemical factors may influence the penetration of the blood-brain barrier. These include pKa values, log-P values, and molecular size. Brain-level measurements indicate that most drugs have some accessibility to the CNS. Maximal effects against sensitive, ic implanted tumors are attained through maximal scheduling. Effective drug combinations should be sought to further enhance antitumor effects in the CNS.

Animals↗