https://www.selleckchem.com/products/OSI-906.html Serum protein interactions are evaluated during the drug development process since they determine the free drug concentration in blood and thereby can influence the drug's pharmacokinetic and pharmacodynamic properties. While the impact of serum proteins on the disposition of small molecules is well understood, it is not yet well characterized for a new modality, RNA interference therapeutics. When administered systemically, small interfering RNAs (siRNAs) conjugated to the N-acetylgalactosamine (GalNAc) ligand bind to proteins present in circulation. However, it is not known if these protein interactions may impact the GalNAc-conjugated siRNA uptake into hepatocytes mediated through the asialoglycoprotein receptor (ASGPR) and thereby influence the activity of GalNAc-conjugated siRNAs. In this study, we assess the impact of serum proteins on the uptake and activity of GalNAc-conjugated siRNAs in primary human hepatocytes. We found that a significant portion of the GalNAc-conjugated siRNAs is bound to serum proteins. However, ASGPR-mediated uptake and activity of GalNAc-conjugated siRNAs were minimally impacted by the presence of serum relative to their uptake and activity in the absence of serum. Therefore, in contrast to small molecules, serum proteins are expected to have minimal impact on pharmacokinetic and pharmacodynamic properties of GalNAc-conjugated siRNAs.Background Aluminum exposure may originate from numerous sources, including antiperspirants. Aluminum toxicity can cause a wide range of neurological impairments. Infants are exposed to aluminum through human milk (HM), formulas, total-parenteral-nutrition and vaccines. Due to potential risk of toxicity to both infants and women, it has been advised that lactating women decrease their use of aluminum-based products and antiperspirants. Our study aimed to determine whether the use of aluminum-based antiperspirants (ABA) affects aluminum levels in HM. Method