British Journal of Biomedical Science (Oct 2024)
Mesoporous Silica Microparticle-Protein Complexes: Effects of Protein Size and Solvent Properties on Diffusion and Loading Efficiency
Abstract
Oral administration of protein-based therapeutics is highly desirable due to lower cost, enhanced patient compliance, and convenience. However, the harsh pH environment of the gastrointestinal tract poses significant challenges. Silica-based carriers have emerged as potential candidates for the delivery of protein molecules, owing to their tuneable surface area and pore volume. We explored the use of a commercial mesoporous silica carrier, SYLOID, for the delivery of octreotide and bovine serum albumin (BSA) using a solvent evaporation method in three different solvents. The loading of proteins into SYLOID was driven by diffusion, as described by the Stokes-Einstein equation. Various parameters were investigated, such as protein size, diffusion, and solubility. Additionally, 3D fluorescence confocal imaging was employed to identify fluorescence intensity and protein diffusion within the carrier. Our results indicated that the loading process was influenced by the molecular size of the protein as octreotide exhibited a higher recovery rate (71%) compared to BSA (32%). The methanol-based loading of octreotide showed uniform diffusion into the silica carrier, whereas water and ethanol loading resulted in the drug being concentrated on the surface, as shown by confocal imaging, and further confirmed by scanning electron microscopy (SEM). Pore volume assessment supported these findings, showing that octreotide loaded with methanol had a low pore volume (1.2 cc/g). On the other hand, BSA loading was affected by its solubility in the three solvents, its tendency to aggregate, and its low solubility in ethanol and methanol, which resulted in dispersed particle sizes of 223 and 231 μm, respectively. This reduced diffusion into the carrier, as confirmed by fluorescence intensity and diffusivity values. This study underscores the importance of protein size, solvent properties, and diffusion characteristics when using porous carriers for protein delivery. Understanding these factors allows for the development of more effective oral protein-based therapeutics by enhancing loading efficiency. This, in turn, will lead to advances in targeted drug delivery and improved patient outcomes.
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