In the realm of modern medicine, the administration of protein-based therapeutics has long presented a formidable challenge. Patients battling cancers, autoimmune diseases, and various metabolic disorders frequently undergo prolonged intravenous (IV) infusions, a method required primarily due to the stability constraints of protein drugs. These biomolecules often must be formulated at low concentrations to maintain their structural integrity, rendering simple injection unfeasible and complicating treatment administration. However, a groundbreaking innovation from Stanford researchers promises to upend this paradigm, introducing a novel delivery system that enables ultra-high concentration protein formulations suitable for rapid, needle-based injection.
Traditionally, protein drugs are administered intravenously over extended durations because high-concentration liquid formulations tend to aggregate, increasing viscosity and jeopardizing both injectability and drug efficacy. The molecular nature of proteins predisposes them to intermolecular interactions when concentrated, promoting clumping or aggregation that can trigger adverse immune responses and compromise therapeutic benefits. Overcoming these stability and viscosity obstacles has been a formidable barrier to alternative delivery routes such as subcutaneous injections, which are widely preferred for their convenience and patient compliance.
The innovation from Stanford centers on a class of polymer excipients that confer unprecedented stability and flow characteristics to protein formulations. The researchers synthesized a polyacrylamide-based copolymer, termed MoNi, notable for its exceptionally high glass transition temperature. This physicochemical property signifies that MoNi remains in a rigid, glassy state across a range of physiological temperatures, effectively preventing the softening typically observed with conventional surfactants. By exploiting MoNi’s glassy nature, the team developed a spray-drying process that envelops individual protein molecules within a polymer shell, akin to a candy-coated chocolate, encapsulating and immobilizing the protein within a protective, inert matrix.
This process starts with mixing aqueous protein solutions with MoNi, which are then aerosolized into microscopic droplets. Subsequent evaporation of the solvent results in microparticles where each protein molecule is isolated and stabilized by the surrounding polymer layer. Upon re-suspension in a compatible carrier liquid that does not dissolve the polymer coating, these microparticles form an injectable suspension with markedly reduced interparticle friction and viscosity. The polymer shell imparts mechanical robustness and prevents protein aggregation, allowing the suspension to flow smoothly through tiny needles, a feat previously unattainable at such high protein concentrations.
The key breakthrough lies in converting the inherently sticky and viscous protein solutions into physically discrete spherical particles with smooth surfaces. These characteristics facilitate particle mobility and reduce flow resistance, enabling rapid and painless administration of protein therapeutics via standard syringes or autoinjectors. This innovation holds transformative potential, transitioning many treatments from clinic-bound intravenous infusions lasting hours to quick injections easily performed at home within seconds.
To validate their platform, the researchers rigorously tested formulations of diverse protein types including human serum albumin, immunoglobulins, and a monoclonal antibody therapeutic developed against COVID-19. Remarkably, the team successfully achieved protein concentrations exceeding 500 mg/mL – a concentration more than double what is typical for liquid injectable forms – without compromising stability or injectability. Stability assessments demonstrated that these dried particle suspensions maintain structural and functional integrity following thermal stressors, including multiple freeze-thaw cycles and prolonged exposure to elevated temperatures, indicating excellent shelf-life potential and robustness in real-world settings.
This technology’s versatility stems from the polymer shell’s mechanical control over particle behavior rather than relying solely on chemical interactions with specific protein sequences. As such, it can be broadly applied across a wide spectrum of biologic drugs, offering a universal platform for ultra-high concentration formulation. The inherent modularity and adaptability of the spray-drying method further enhance its appeal, enabling rapid customization for varied therapeutic agents and dosages.
Beyond the laboratory, MoNi and the associated spray drying technique have already passed preclinical safety evaluations with no detectable adverse effects, supporting translational feasibility. The researchers have licensed this technology to a startup dedicated to refining the manufacturing processes and accelerating its commercial development, with an aim toward regulatory approval and clinical adoption. This promising transition could spur the arrival of a new generation of injectable biologics characterized by convenience, efficacy, and improved patient quality of life.
The clinical and societal implications of such a platform are profound. For patients, the capacity to self-administer treatments previously restricted to specialized infusion clinics represents an enormous reduction in time, cost, and logistical burden. Moreover, shifting to autoinjector-based delivery can enhance patient adherence, improve therapeutic outcomes, and reduce healthcare system strain. In essence, it democratizes access to advanced protein therapies while extending their therapeutic utility.
According to Eric Appel, associate professor at Stanford and senior author of the study, “Our platform can work with any biologic drug, transforming treatments from multihour hospital infusions into simple injections performed at home.” Co-first author Carolyn Jons elaborates on the mechanical insights behind the formulation, emphasizing how “the spherical microparticles’ smoothness and independence allow them to flow easily through tiny needles even at very high drug concentrations.” Complementing these perspectives, Alexander Prossnitz highlights the significance of mechanical properties over molecular chemistry in ensuring drug stability, illuminating a new avenue for drug formulation innovation.
In summary, the deployment of a glassy polymer excipient such as MoNi in the spray drying of protein therapeutics delineates a revolutionary approach to biologic drug delivery. This platform reconciles the conflicting demands of high drug concentration, stability, and injectability, thus addressing a longstanding bottleneck in pharmaceutical development. As this technology matures toward clinical application, we stand on the cusp of a transformation that will enable faster, easier, and more effective protein-based treatments, ultimately reshaping patient care in oncology, immunology, and beyond.
Subject of Research: Development of ultra-high concentration protein therapeutics using spray drying with a glassy surfactant excipient.
Article Title: Ultra-high concentration biologic therapeutics enabled by spray drying with a glassy surfactant excipient.
News Publication Date: 20-Aug-2025
Web References:
– https://doi.org/10.1126/scitranslmed.adv6427
References:
– Published article in Science Translational Medicine, August 20, 2025, by Eric Appel and colleagues at Stanford University.
Image Credits: Carolyn Jons
Keywords: Drug delivery, Routes of administration, Medical treatments, Materials science, Pharmaceutical formulation, Protein therapeutics, Spray drying, Biologics, Polymer excipients, Injectable suspensions
