Protein therapeutics, particularly antibodies, depend on maintaining their native structures for optimal function. Hydrophobic interfaces, such as the air-water interface, can trigger protein aggregation and denaturation. While completely avoiding such interfacial exposures during manufacturing and storage is impractical, minimizing them is crucial for enhancing protein drug stability and extending shelf life. In the biologics industry, surfactants like polysorbates are commonly used as additives (excipients) to mitigate these undesirable interfacial exposures. However, polysorbates, the most prevalent choice, have recognized limitations in terms of polydispersity, purity, and stability, prompting the exploration of alternative excipients. The present study identifies poly(N-isopropylacrylamide)-poly(ethylene glycol) (PNIPAM-PEG) block copolymers as a promising alternative to polysorbates. Due to its stronger affinity for the air-water interface, PNIPAM-PEG significantly outperforms polysorbates in enhancing protein stability. This claim is supported by results from multiple tests. Accelerated dynamic light scattering (DLS) experiments demonstrate PNIPAM-PEG's exceptional efficacy in preserving IgG stability against surface-induced aggregation, surpassing conventional polysorbate excipients (Tween 80 and Tween 20) under high-temperature conditions. Additionally, circular dichroism (CD) spectroscopy results reveal conformational alterations associated with aggregation, with PNIPAM-PEG consistently demonstrates a greater protective effect by mitigating negative shifts at λ ≅ 220 nm, indicative of changes in secondary structure. Overall, this study positions PNIPAM-PEG as a promising excipient for antibody therapeutics, facilitating the development of more stable and effective biopharmaceuticals.
Keywords: Excipient; IgG antibody; PNIPAM-PEG; Protein biologic; Stability.
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