C&EN’s Post

Great story from C&EN! For more on why researchers and pharmaceutical companies are interested in antibody-drug conjugates, check out our CAS Insights article https://lnkd.in/e3mpb_SH

Thinking on linkers for #antibodydrugconjugates 👇 C&EN discuss how a linker may be a small part of an antibody-drug conjugate, but drugmakers are finding that linker chemistry is important. Read the article below 👇 https://lnkd.in/dXNpwqbq

https://lnkd.in/gU_W96bE Complex Generics: Physicochemical Characterization Analysis for Deformulation and In Vitro Bioequivalence Studies

𝗡𝗮𝗻𝗼𝗹𝗶𝗽𝗼𝘀𝗼𝗺𝗲𝘀 𝗣𝗲𝗿𝗺𝗲𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗶𝗻 𝗮 𝗠𝗶𝗰𝗿𝗼𝗳𝗹𝘂𝗶𝗱𝗶𝗰 𝗗𝗿𝘂𝗴 𝗗𝗲𝗹𝗶𝘃𝗲𝗿𝘆 𝗣𝗹𝗮𝘁𝗳𝗼𝗿𝗺 𝗮𝗰𝗿𝗼𝘀𝘀 𝗮 𝟯𝗗 𝗛𝘆𝗱𝗿𝗼𝗴𝗲𝗹 Nanoliposomes are nano-sized vesicles that can be used as drug delivery carriers with the ability to encapsulate both hydrophobic and hydrophilic compounds. Moreover, their lipid compositions facilitate their internalization by cells. However, the interaction between nanoliposomes and the membrane barrier of the human body is not well-known. If cellular tests and animal testing offer a solution, their lack of physiological relevance and ethical concerns make them unsuitable to properly mimic human body complexity. Microfluidics, which allows the environment of the human body to be imitated in a controlled way, can fulfil this role. However, existing models are missing the presence of something that would mimic a basal membrane, often consisting of a simple cell layer on a polymer membrane. In this study, we investigated the diffusion of nanoliposomes in a microfluidic system and found the optimal parameters to maximize their diffusion. Then, we incorporated a custom made GelMA with a controlled degree of substitution and studied the passage of fluorescently labeled nanoliposomes through this barrier. Our results show that highly substituted GelMA was more porous than lower substitution GelMA. Overall, our work lays the foundation for the incorporation of a hydrogel mimicking a basal membrane on a drug delivery microfluidic platform. Read more here: https://lnkd.in/eRMvkxd8 #excipients #nano #microfluidic

Achieving oral bioavailability with Proteolysis Targeting Chimeras (PROTACs) is a key challenge. Here, we report the in vivo pharmacokinetic properties in mouse, rat, and dog of four clinical oral PROTACs and compare with an internally derived data set. We use NMR to determine 3D molecular conformations and structural preorganization free in solution, and we introduce the new experimental descriptors, solvent-exposed H-bond donors (eHBD), and acceptors (eHBA). We derive an upper limit of eHBD ≤ 2 for oral PROTACs in apolar environments and show a greater tolerance for other properties (eHBA, polarity, lipophilicity, and molecular weight) than for Rule-of-5 compliant oral drugs. Within a set of structurally related PROTACs, we show that examples with eHBD > 2 have much lower oral bioavailability than those that have eHBD ≤ 2. We summarize our findings as an experimental “Rule-of-oral-PROTACs” in order to assist medicinal chemists to achieve oral bioavailability in this challenging space.

For those interested in the expanding and advancing uses of nanoparticles as drug delivery vehicles, this report by Alexander Aust, MS, MBA and Abigael Frederick provides a fine overview of the current landscape of delivery technologies and therapeutic targets for LNP (lipid nanoparticle)-based and PNP (polymer nanoparticle)-based systems. #drugdelivery #nanoparticles #advancedtherapies https://lnkd.in/d6WxEtiK

Studies have shown Fibrinogen testing to be an effective measure to take when diagnosing and monitoring Hemophilia. Explore Diazyme’s Fibrinogen Test- This test also helps doctors assess a patient’s ability to form a blood clot. This test is ordered either along with other tests or when a patient has an abnormal PT or APTT test result, or both. Diazyme’s Fibrinogen Assay is a cost-effective dual vial liquid stable. immunoturbidimetric reagent system intended for the in vitro quantitative determination of fibrinogen levels in citrated human plasma. Runs on Clinical Chemistry Analyzers! Learn more today: https://lnkd.in/gRDpCYTB #WorldHemophiliaDay #ClinicalChemistry #CoagulationMarkers #InnovativeSolutions

Interested in Analytical Characterization of Biosimilars During Development? Orthogonal Analysis Using Ligand Binding Kinetics & Live Cell Binding https://lnkd.in/gbaceYJ2 #biosimilars #ligandbinding #kinetics #livecellanalysis #biotherapeutics

Have you ever wondered why TR-FRET is not popular for measuring antibody-antigen binding? My student Harmon Greenway delved into this question and figured out that monovalent tracers (dye-conjugated Fab) should be used instead of bivalent tracers (dye-conjugated mAb). He performed a lot of simulations to understand the tight binding problem. We believe this can be a cheap and high throughput assay for antibody-drug conjugates quality control. Read here if you are interested: https://lnkd.in/eMYJShRb #drugdiscovery #ADCs #TRFRET

Analytical characterization of the antibody drug conjugate ( ADC ) Enhertu using multi-capillary electrophoresis.