A5005936771- Protein purification and stability
- Advanced biosensing and bioanalysis techniques
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Electrochemical Analysis and Applications
- Analytical Chemistry and Chromatography
- 3D Printing in Biomedical Research
- MicroRNA in disease regulation
- DNA and Nucleic Acid Chemistry
- Conducting polymers and applications
- Photochemistry and Electron Transfer Studies
- Porphyrin and Phthalocyanine Chemistry
- Drug Solubulity and Delivery Systems
- Ionic liquids properties and applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Advanced NMR Techniques and Applications
- Microfluidic and Capillary Electrophoresis Applications
- Electrochemical sensors and biosensors
- Glycosylation and Glycoproteins Research
- Mineral Processing and Grinding
- Fault Detection and Control Systems
- Neurological Complications and Syndromes
- Firm Innovation and Growth
- Dendrimers and Hyperbranched Polymers
Bristol-Myers Squibb (United States)
2018-2025
The Bristol-Myers Squibb Children's Hospital
2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2014-2019
United States Military Academy
2012-2016
Merck (Japan)
2005
University of North Carolina at Chapel Hill
2000-2005
Lawrence Berkeley National Laboratory
1988
University of California, Berkeley
1988
University of the Pacific
1988
It has been technically challenging to specify the detailed molecular interactions and binding motif between drugs polymeric inhibitors in solid state. To further investigate drug-polymer from a perspective, dispersion of clofazimine (CLF) hypromellose phthalate (HPMCP), with reported superior amorphous drug loading capacity physical stability, was selected as model system. The CLF-HPMCP dispersions were investigated by various state spectroscopic methods including ultraviolet-visible...
A principal advantage of magic angle spinning (MAS) NMR spectroscopy lies in its ability to determine molecular structure a noninvasive and quantitative manner. Accordingly, MAS should be widely applicable studies the active pharmaceutical ingredients (API) formulations. However, low sensitivity encountered natural abundance APIs present at concentration has limited success experiments. Dynamic nuclear polarization (DNP) enhances can used circumvent this problem provided that suitable...
The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation decomposition thermally sensitive components. Herein, the rheological properties a physical mixture polymer an active pharmaceutical ingredient (API) were utilized to guide selection appropriate HME processing temperature. In currently studied copovidone–nifedipine system, critical temperature, is substantially lower...
The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography–mass spectrometry application. Successful implementation purity-indicating assay requires new peak detection (NPD) potential process- and/or product-related impurities. NPD interlaboratory study described herein...
Ionic liquids are described that contain duplex DNA as the anion and polyether-decorated transition metal complexes based on M(MePEG-bpy)32+ cation (M = Fe, Co; MePEG-bpy 4,4'-(CH3(OCH2CH2)7OCO)2-2,2'-bipyridine). When undiluted liquid DNAor molten saltis interrogated electrochemically by a microelectrode, salts exhibit cyclic voltammograms due to physical diffusion (DPHYS) of polyether−transition complex. M Co(II), voltammogram melt shows an oxidative wave Co(III/II) couple at E1/2 0.40 V...
The development of lipid nanoparticle (LNP) based small interfering RNA (siRNA) therapeutics presents unique pharmaceutical and regulatory challenges. In contrast to molecule drugs that are highly pure well-defined, LNP drug products can exhibit heterogeneity in size, composition, surface property, or morphology. potential for batch introduces a complexity must be confronted order successfully develop ensure quality pharmaceuticals. Currently, there is lack scientific knowledge the LNPs as...
Efficient siRNA delivery is dependent not only on the ability of vehicle to target a specific organ but also its enable entry into cytoplasm cells. Polymers with endosomolytic properties are increasingly being used as vehicles due their potential facilitate endosomal escape and intracellular delivery. Addition disulfide bonds in backbone these polymers was expected provide degradability through reduction by glutathione cytosol. This paper describes synthesis new bioreducible poly(amido amine...
Liquid chromatography–mass spectrometry (LC-MS)-based proteomics approaches have been widely used to identify residual host-cell proteins (HCPs) in support of process and product characterization for protein therapeutics. Particularly, these methods can provide a general unbiased approach the detection HCPs may generate critical information on that are outside coverage provided by conventional immunoassay. A significant technical hurdle HCP analysis is overwhelmingly large background...
ABSTRACT This study emphasizes the critical importance of closely monitoring and controlling sialic acid content in therapeutic glycoproteins, including EPO, interferon‐γ, Orencia, Enbrel, others, as level sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes binds glycoproteins exposed terminal galactose or...
A primary consideration when developing lipid nanoparticle (LNP) based small interfering RNA (siRNA) therapeutics is formulation polydispersity or heterogeneity. The level of heterogeneity physicochemical properties within a pharmaceutical batch could greatly affect the bioperformance, quality, and ability manufacturer to consistently control reproduce formulations. This article studied in size, composition, vitro performance siRNA containing LNPs, by conducting preparative scale...
Tryptophan's (Trp) unique hydrophobic and structural properties make it an important antigen binding motif when positioned in complementarity-determining regions (CDRs) of monoclonal antibodies (mAbs). Oxidation Trp residues within the CDR can deleteriously impact binding, particularly if conformation is altered. The goal this study was to evaluate conformational functional oxidation for two mAb subtypes, which essential determining structure-function relationship establishing appropriate...
The application of small interfering (si)RNAs as potential therapeutic agents requires safe and effective methods for their delivery to the cytoplasm target cells tissues. Recent studies have shown significant progress in development targeting reagents that facilitate recognition of, siRNA to, specific cell types. Among recently reported approaches, polymers with amphipathic properties been used enable endosome escape cytosolic delivery. Here, we describe a linear poly(amido amine) polymer...
Rationale Multi‐Attribute Methods (MAMs) are appealing due to their ability provide data on multiple molecular attributes from a single assay. If fully realized, such tests could reduce the number of assays required support product control strategy while providing equivalent or greater understanding relative conventional approach. In doing so, MAMs have potential decrease development and manufacturing costs by reducing in release panel. this work, we report MAM which is based subunit mass...
Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents vitro and vivo; however, most suffer from cytotoxicity due part a lack of selectivity for versus cell membrane lysis. For polymer move beyond the laboratory into clinic, it is critical find are not only efficacious, but also margins clinically relevant. In this paper we report three distinct categories conjugates improve lysis by relying on change pH associated with trafficking, including...
The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted traditional peptide mapping methods; it leverages mass spectrometry (MS) detection confident identification quantitation of many types attributes may be targeted monitoring. While has widely explored across the industry, yet gain strong foothold within QC...