Various formulations consisting of biomaterials zirconium imidazolate framework-8 (ZIF-8), choline acetate ([Ch][Ac]), and arginine hydrochloride (argHCl) are optimized to study the stability of antibody, Immunoglobulin G (IgG). We have performed several instrumentations including UV-visible spectroscopy, dynamic light scattering (DLS), circular dichroism (far UV CD), and atomic force microscopy (AFM) in the presence of all the formulations to investigate the conformational and colloidal stability of the antibodies. Alongside, the packing efficiency of all the formulations was also explored by storing IgG at 4 °C for 3 months. We have tried to investigate the interactions between biomaterials and antibodies with the motive of designing aggregation-resistant formulations. The overall stability of IgG was improved in the presence of [Ch][Ac]; however, ZIF-8 and argHCl cause relatively more aggregation, although the structure was retained in all the formulations. The key aspect of this study is that the presence of [Ch][Ac] increases ZIF-8@IgG's thermal stability and resistance to IgG-argHCl aggregation. All over, for the first time, with different experimental approaches, the impact of each biomaterial individually and in combination is explored to study their effect on the stability of antibodies. Thus, better efficient formulations can be designed for the storage/packaging of IgG-based drugs which ultimately will have more applicability in pharmaceuticals.
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http://dx.doi.org/10.1021/acs.molpharmaceut.3c00167 | DOI Listing |
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.
Antibody-drug conjugates (ADCs) have emerged as a promising strategy in targeted cancer therapy, enabling the precise delivery of cytotoxic agents to tumor sites while minimizing systemic toxicity. However, traditional ADCs face significant limitations, including restricted drug loading capacity, where an optimal drug-to-antibody ratio (DAR) is crucial; low DARs may lead to insufficient potency, while high DARs can cause rapid clearance and increased toxicity. Additionally, ADCs often suffer from instability in circulation due to the potential for premature release of cytotoxic agents, resulting in off-target effects and reduced therapeutic efficacy.
View Article and Find Full Text PDFAnal Methods
September 2020
College of Life Sciences, Fujian Normal University, Fuzhou 350117, Fujian, China.
An innovative magnetic immunoassay was developed for the voltammetric detection of carbohydrate antigen-125 (CA-125) on a home-made microfluidic device including a multisyringe pump, selection valve and magneto-controlled detection cell. Two kinds of biofunctionalized nanostructures including anti-CA-125 capture antibody-conjugated magnetic beads and anti-CA-125 detection antibody-labeled silver-polypyrrole (Ag-PPy) nanohybrids were utilized for a sandwiched immunoreaction in the presence of CA-125. With the help of an external magnet, the formed magnetic immunocomplexes were attached to the sensing interface to activate the electrical contact between Ag-PPy nanohybrids and the base electrode, thus resulting in the switching on of the sensor circuit for the generation of voltammetric signals thanks to electroactive Ag-PPy nanohybrids.
View Article and Find Full Text PDFAAPS J
January 2025
Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Freeze drying is one of the common methods to extend the long-term stability of biologicals. Biological products in solid form have the advantages of convenient transportation and stable long-term storage. However, long reconstitution time and extensive visible bubbles are frequently generated during the reconstitution process for many freeze-dried protein formulations, which can potentially affect the management efficiency of staff, patient compliance, and product quality.
View Article and Find Full Text PDFPharm Res
January 2025
BioDev Department WuXi Biologics USA, 1 Cedarbrook Dr, Cranbury, NJ, 08512, USA.
Background: High concentration protein formulation (HCPF) development needs to balance protein stability attributes such as conformational/colloidal stability, chemical stability, and solution properties such as viscosity and osmolality.
Methodology: A three-phase design is established in this work. In Phase 1, conformational and colloidal stability are measured by 384-well-based high-throughput (HT) biophysical screening while viscosity reduction screening is performed with HT viscosity screening.
Nat Struct Mol Biol
January 2025
Zhejiang Provincial Key Laboratory of Pancreatic Disease, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.
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