Disordered mesoporous silica particles: an emerging platform to deliver proteins to the lungs

• Published in: Drug delivery Vol. 31; no. 1; p. 2381340
• Main Authors: Rocío Hernández, Aura, Bogdanova, Ekaterina, Campos Pacheco, Jesus E, Kocherbitov, Vitaly, Ekström, Mikael, Pilkington, Georgia, Valetti, Sabrina
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: Administration, Inhalation; Animals; Chemistry, Pharmaceutical - methods; Dried powder inhalation; Drug Carriers - chemistry; Drug Delivery Systems - methods; Excipients - chemistry; Freeze Drying; Humans; Lung - drug effects; Lung - metabolism; mesoporous silica particles; micronised drug carrier; Muramidase - administration & dosage; Muramidase - chemistry; Nanoparticles - chemistry; Particle Size; Porosity; Powders - chemistry; protein formulation; pulmonary drug delivery; Silicon Dioxide - chemistry; Spectroscopy, Fourier Transform Infrared; protein formulation; micronised drug carrier; mesoporous silica particles; Dried powder inhalation; pulmonary drug delivery
• ISSN: 1071-7544; 1521-0464; 1521-0464
• DOI: 10.1080/10717544.2024.2381340

Pulmonary delivery and formulation of biologics are among the more complex and growing scientific topics in drug delivery. We herein developed a dry powder formulation using disordered mesoporous silica particles (MSP) as the sole excipient and lysozyme, the most abundant antimicrobial proteins in the airways, as model protein. The MSP had the optimal size for lung deposition (2.43 ± 0.13 µm). A maximum lysozyme loading capacity (0.35 mg/mg) was achieved in 150 mM PBS, which was seven times greater than that in water. After washing and freeze-drying, we obtained a dry powder consisting of spherical, non-aggregated particles, free from residual buffer, or unabsorbed lysozyme. The presence of lysozyme was confirmed by TGA and FT-IR, while N adsorption/desorption and SAXS analysis indicate that the protein is confined within the internal mesoporous structure. The dry powder exhibited excellent aerodynamic performance (fine particle fraction <5 µm of 70.32%). Lysozyme was released in simulated lung fluid in a sustained kinetics and maintaining high enzymatic activity (71-91%), whereas LYS-MSP were shown to degrade into aggregated nanoparticulate microstructures, reaching almost complete dissolution (93%) within 24 h. MSPs were nontoxic to lung epithelium. The study demonstrates disordered MSP as viable carriers to successfully deliver protein to the lungs, with high deposition and retained activity.