While mesoporous silicas have been shown to be a compelling candidate for drug delivery and the implementation of biotechnological applications requiring protein confinement and immobilization, the understanding of protein behavior upon physical adsorption into silica pores is limited. Many indirect methods are available to assess general adsorbed protein stability, such as Fourier-transform infrared spectroscopy and activity assays. However, the limitation of these methods is that spatial protein arrangement within the pores cannot be assessed. Mesoporous silicas pose a distinct challenge to direct methods, such as transmission electron microscopy, which lacks the contrast and resolution required to adequately observe immobilized protein structure, and nuclear magnetic resonance, which is computationally intensive and requires knowledge of the primary structure a priori. Small-angle neutron scattering can surmount these limitations and observe spatial protein arrangement within pores. Hereby, we observe the stabilization of fluid-like protein arrangement, facilitated by geometry-dependent crowding effects in cylindrical pores of ordered mesoporous silica, SBA-15. Stabilization is induced from a fluid-like structure factor, which is observed for samples at maximum protein loading in SBA-15 with pore diameters of 6.4 and 8.1 nm. Application of this effect for prevention of irreversible aggregation in high concentration environments is proposed.

IntroductionConfinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants.Areas coveredMesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments.Expert opinionThe SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.