Bovine serum albumin (BSA) protein is widely used to fabricate antifouling coatings for nanobiotechnology applications. Numerous BSA protein options are commercially available and obtained through different purification methods, however, there is no guidance on which ones are preferable for antifouling coatings. Herein, we investigate the real-time fabrication of antifouling coatings composed of BSA proteins obtained through different purification methods, and report significant differences in ultrathin film coating properties and ability to mitigate serum biofouling and to prevent nanoparticle-induced immune reactions. Mechanistic studies unravel the source of these performance variations, which are related to some BSA proteins containing fatty acid stabilizers while other BSA proteins are fatty acid-free depending on the purification method. Fatty acid-free BSA proteins exhibit greater conformational flexibility and less charge repulsion, which allow them to form more rigidly attached and tightly packed coatings on flat surfaces and nanoparticles that result in superior application performance.

Pharmaceutical drugs and vaccines require the use of material containers for protection, storage, and transportation. Glass and plastic materials are widely used for packaging, and a longstanding challenge in the field is the nonspecific adsorption of pharmaceutical drugs to container walls – the so‐called “sticky containers, vanishing drugs” problem – that effectively reduces the active drug concentration and can cause drug denaturation. This challenge has been frequently discussed in the case of the anticancer drug, paclitaxel, and the ongoing coronavirus disease 2019 (COVID‐19) pandemic has brought renewed attention to this material science challenge in light of the need to scale up COVID‐19 vaccine production and to secure sufficient quantities of packaging containers. To reduce nonspecific adsorption on inner container walls, various strategies based on siliconization and thin polymer films have been explored, while it would be advantageous to develop mass‐manufacturable, natural material solutions, especially ones involving pharmaceutical grade excipients. Inspired by how lipid nanoparticles have revolutionized the vaccine field, in this perspective, we discuss the prospects for developing lipid bilayer coatings to prevent nonspecific adsorption of pharmaceutical drugs and vaccines and how recent advances in lipid bilayer coating fabrication technologies are poised to accelerate progress in the field. We critically discuss recent examples of how lipid bilayer coatings can prevent nonspecific sticking of proteins and vaccines to relevant material surfaces and examine future translational prospects.