Article
Chemistry, Physical
Kiet G. Pham, Benjamin R. Thompson, Tingting Wang, Shayak Samaddar, Ken K. Qian, Yun Liu, Norman J. Wagner
Summary: By measuring the interfacial viscoelasticity and surface pressure of mAbs at the air-water interface, we can predict their long-term stability, which is crucial in the pharmaceutical industry.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Medicinal
Aadithya Kannan, Ian C. Shieh, Petar Hristov, Gerald G. Fuller
Summary: The use of monoclonal antibodies (mAbs) for disease treatment is increasing rapidly, with a higher aggregation propensity observed in saline compared to low ionic strength formulation buffer. The presence of salt in buffer with surfactants leads to greater mAb adsorption at the interface and the formation of more particulate aggregates. Stress studies for mAb formulations intended for intravenous administration should be performed in conditions representative of their intended route of administration.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Aadithya Kannan, Ian C. Shieh, Patrick G. Negulescu, Vineeth Chandran Suja, Gerald G. Fuller
Summary: This study shows that different antibodies have different surface activities at oil-water interfaces, directly affecting their aggregation at the interface. The addition of surfactants can competitively lower the adsorption and aggregation of antibodies at the interface, thus stabilizing the antibody formulations.
MOLECULAR PHARMACEUTICS
(2021)
Article
Chemistry, Medicinal
Kohei Soeda, Masakazu Fukuda, Masaya Takahashi, Hirotaka Imai, Kengo Arai, Satoshi Saitoh, Ravuri S. K. Kishore, Nuria Sancho Oltra, Jeremy Duboeuf, Daisuke Hashimoto, Yuji Yamanaka
Summary: This study demonstrates the importance of hydrophobicity of Poloxamer 188 (PX188) in controlling visible particle (VP) formation in biotherapeutic formulations. The variability in hydrophobicity among different PX188 lots can affect surfactant function and VP formation. Monitoring lot-to-lot variability of PX188 is crucial for improving and controlling its material attributes in liquid biotherapeutic formulations.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Kohei Soeda, Kengo Arai, Tetsuya Yamamoto, Katsuya Ofuji, Masakazu Fukuda, Daisuke Hashimoto, Yuji Yamanaka
Summary: The formation of visible particles (VPs) in liquid monoclonal antibody formulations is a significant quality concern. This study investigates the mechanisms of protein-polydimethylsiloxane (PDMS) VP formation and identifies the dominant spot and pathway in a specific vial formulation. Factors such as drug solution adhesion, storage orientation, silicone coating, vial material, and surfactant hydrophobicity have a notable impact on VP formation. The findings contribute to a better understanding of VP formation mechanisms and provide strategies for mitigating VPs in biotherapeutics.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Shravan Sreenivasan, Wim Jiskoot, Anurag S. Rathore
Summary: The degradation of therapeutic monoclonal antibodies (mAb) due to interfacial agitation through air bubbling was investigated. It was found that exposure to air/liquid interfacial stress effectively generated sub-visible and visible aggregates in mAb samples, impacting protein structure and activity.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Medicine, Research & Experimental
Ankit D. Kanthe, Miriam R. Carnovale, Joshua S. Katz, Susan Jordan, Mary E. Krause, Songyan Zheng, Andrew Ilott, William Ying, Wei Bu, Mrinal K. Bera, Binhua Lin, Charles Maldarelli, Raymond S. Tu
Summary: This study aimed to investigate the competitive adsorption mechanism between proteins and surfactants, finding that FM1000 saturates the interface faster than PS80 and is more effective in preventing protein adsorption.
MOLECULAR PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Kai Zheng, Diya Ren, Y. John Wang, Wayne Lilyestrom, Thomas Scherer, Justin K. Y. Hong, Junyan A. Ji
Summary: Oxidation is a key degradation pathway for protein drugs, which can impact product efficacy and patient safety. This study found that oxidation led to the oxidation of methionine and tryptophan residues, as well as increased protein aggregation. Excipients such as tryptophan, pyridoxine, or tyrosine were shown to effectively reduce protein aggregation induced by oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Zhen-Yi Jing, Guo-Li Huo, Min-Fei Sun, Bin-Bin Shen, Wei-Jie Fang
Summary: The primary objectives of this study were to investigate the degradation mechanisms of freeze-dried monoclonal antibody formulations under mechanical grinding, assess the sensitivity and suitability of various particle analysis techniques, analyze the structure of the collected subvisible particles, and analyze the antioxidant mechanism of methionine under degradation process to gain a thorough understanding of the phenomenon.
PHARMACEUTICAL RESEARCH
(2022)
Article
Biochemical Research Methods
Izabela Poplewska, Wojciech Piatkowski, Dorota Antos
Summary: A mechanistic model for describing the unfolding of a monoclonal antibody in ion exchange chromatography has been developed. The model reproduced retention behavior characteristic for conformational changes of antibodies, including multi-peak elution, aggregate formation, and recovery reduction. The model was formulated based on the analysis of retention behavior of a model mAb that was eluted in pH gradients on a strong cation exchange resin, and it can potentially be used to quantify protein unfolding and elution in other ion exchange systems.
JOURNAL OF CHROMATOGRAPHY A
(2021)
Article
Chemistry, Medicinal
Arthur J. Schick, Li Yi, Philippe Lam, Preston Pallante, Nathaniel Swanson, Jacqueline Y. Tyler
Summary: Sterile filtration is a critical step in the manufacturing process of biological therapeutics, but protein adsorption to filter surfaces can lead to issues. By adjusting the Debye screening length parameters of the solution, the loss of high molecular weight species during filtration can be influenced.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Sachini P. Karunaratne, Madeleine C. Jolliffe, Isabelle Trayton, Ramesh Kumar Shanmugam, Nicholas J. Darton, David D. Weis
Summary: Multidose formulations have advantages over single-dose formats. The selection of antimicrobial preservatives is challenging in terms of maintaining drug product stability. The study found that the addition of antimicrobial preservatives decreased conformational stability.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Applied
Bo Chen, Xiaoyan Liu, Kai Zhou, Yong Xie, Ying Wang, Hui Zhou, Yanhong Bai, Baocai Xu
Summary: The study investigated the effects of modulating hydrophobic interaction and disulfide bond on the properties of myofibrillar protein emulsion gels at high temperature. It also differentiated the contribution of non-covalent (hydrophobic interaction) and covalent intermolecular interactions (disulfide bond) to interfacial protein films. The results showed that modulating hydrophobic interaction or disulfide bonds improved the properties of the myofibrillar protein emulsion gels at 95 degrees C, with changes in interfacial adsorption patterns and emphasis on gel matrix improvement and stiffness increase of interfacial protein films.
Review
Chemistry, Physical
Beibei Zhou, John T. Tobin, Stephan Drusch, Sean A. Hogan
Summary: The interfacial properties of dairy proteins are of great interest to the food industry. Various environmental conditions and processes significantly affect the structure and stability of food materials. Further studies may help in designing better interfacial protein structures for different food applications.
ADVANCES IN COLLOID AND INTERFACE SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Abu Zayed Md Badruddoza, Thean Yeoh, Jaymin C. Shah
Summary: In this study, topical gel and emulsion gel were formulated using Acrylamide/ Sodium Acryloyldimethyl taurate copolymer (Sepineo P600) as a gelling agent. The study evaluated their rheological properties and physical stability upon incorporation of API. It was found that the rheological properties were significantly influenced by the pH and API concentration, and electrostatic attraction between API and polymer played a major role in altering the rheology.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biotechnology & Applied Microbiology
Jared S. Bee, LeeAnn M. Machiesky, Li Peng, Kristin C. Jusino, Matthew Dickson, Jeffrey Gill, Douglas Johnson, Hung-Yu Lin, Kenneth Miller, Jenny Heidbrink Thompson, Richard L. Remmele
BIOTECHNOLOGY PROGRESS
(2017)
Article
Biochemistry & Molecular Biology
Srinath Kasturirangan, G. Jonah Rainey, Linda Xu, Xinwei Wang, Alyse Portnoff, Tracy Chen, Christine Fazenbaker, Helen Zhong, Jared Bee, Zhutian Zeng, Craig Jenne, Herren Wu, Changshou Gao
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Flaviu Gruia, Arun Parupudi, Manuel Baca, Chris Ward, Andrew Nyborg, Richard L. Remmele, Jared S. Bee
JOURNAL OF PHARMACEUTICAL SCIENCES
(2017)
Article
Biochemistry & Molecular Biology
Vaheh Oganesyan, Li Peng, Jared S. Bee, John Li, Samuel R. Perry, Frank Comer, Linda Xu, Kimberly Cook, Kannaki Senthil, Lori Clarke, Kim Rosenthal, Changshou Gao, Melissa Damschroder, Herren Wu, William Dall'Acqua
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Grzegorz Kijanka, Jared S. Bee, Samuel A. Korman, Yuling Wu, Lorin K. Roskos, Mark A. Schenerman, Bram Slutter, Wim Jiskoot
JOURNAL OF PHARMACEUTICAL SCIENCES
(2018)
Article
Chemistry, Medicinal
Mandi M. Hopkins, Cherie L. Lambert, Jared S. Bee, Arun Parupudi, David L. Bain
JOURNAL OF PHARMACEUTICAL SCIENCES
(2018)
Article
Biotechnology & Applied Microbiology
Swarnim Ranjan, Wai Keen Chung, Romina Hofele, Jenny Heidbrink Thompson, Jared Bee, Limin Zhang, David Robbins, Steven M. Cramer
BIOTECHNOLOGY AND BIOENGINEERING
(2019)
Article
Chemistry, Medicinal
Grzegorz Kijanka, Jared S. Bee, Mark A. Schenerman, Samuel A. Korman, Yuling Wu, Bram Stutter, Wim Jiskoot
JOURNAL OF PHARMACEUTICAL SCIENCES
(2020)
Article
Medicine, Research & Experimental
Jun Kim, Yoen Joo Kim, Mingyan Cao, Niluka De Mel, Kenneth Miller, Jared S. Bee, Jihong Wang, Xiangyang Wang, Methal Albarghouthi
Article
Chemistry, Multidisciplinary
Mandi M. Hopkins, Arun Parupudi, Jared S. Bee, David L. Bain
Summary: This study investigated the thermodynamics of reversible self-association (RSA) for two monoclonal antibodies (mAbs C and E) showing strong evidence of RSA, using dynamic light scattering and sedimentation velocity studies. The results revealed that mAb C undergoes isodesmic self-association driven by enthalpy, while mAb E undergoes monomer-dimer self-association driven by entropy with minimal enthalpic contribution. The study also discussed the classical interpretations involving van der Waals and electrostatic interactions for mAbs C and E, respectively, as well as the limitations of these interpretations due to potential additional equilibria coupling with RSA.
PHARMACEUTICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Yu (Zoe) Zhang, Roberto A. DePaz, Jared S. Bee, Tristan Marshall
Summary: The study developed a lyophilized AAV formulation that maintained stability for 24 months, showcasing the feasibility of a dried formulation for AAV gene therapy. By optimizing the composition and residual moisture range, as well as utilizing sucrose, citrate, and glycerol, AAV8 was protected from degradation and potency loss.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Chemistry, Medicinal
Jared S. Bee, Kristin O'Berry, Yu (Zoe) Zhang, Megan Kuhn Phillippi, Akanksha Kaushal, Roberto A. DePaz, Tristan Marshall
Summary: The study investigated the release of free DNA from AAV vectors under various conditions, showing that free DNA gradually increased under high temperature, freeze/thaw cycles, and long-term storage. A sensitive fluorescent dye method was developed to detect and quantify the release of free DNA, which revealed a relatively minor degradation pathway for free DNA release under different conditions.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Medicinal
Jared S. Bee, Yu (Zoe) Zhang, Megan Kuhn Phillippi, Sheyla Finkner, Tesfu Mezghebe, Keith Webber, Win Den Cheung, Tristan Marshall
Summary: There is an increasing number of clinical studies evaluating different AAV serotypes as vectors for gene therapy. The stability profiles of AAV8 and AAV9 are suitable for manufacturing and clinical development.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Jared S. Bee, Yu Zhang (Zoe), Sheyla Finkner, Kristin O'Berry, Akanksha Kaushal, Megan Kuhn Phillippi, Roberto A. DePaz, Keith Webber, Tristan Marshall
Summary: Gene therapies using adeno-associated virus (AAV) vectors have great potential. This study investigates the mechanisms of AAV capsid rupture during freeze-thaw (F/T) cycles and proposes three formulation mitigation approaches to stabilize AAV.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Meeting Abstract
Chemistry, Multidisciplinary
Swarnim Ranjan, Wai Keen Chung, Jared Bee, Romina Hofele, Jenny HeidbrinkThompson, Min Zhu, David Robbins, Steven Cramer
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2017)