Vignesh Muthuvijayan

In this study, a pH-induced self-assembly-based method has been developed to form silk fibroin nanoparticles (SFN-2) with a higher drug loading capacity (21.0 ± 2.1%) and cellular uptake than that of silk fibroin particles produced by a conventional desolvation method (SFN-1). Using the self-assembly method, rifampicin-encapsulated silk fibroin nanoparticles (R-SFN-2) were prepared with a size of 165 ± 38 nm at an optimum pH of 3.8. In silico analysis reveals that at acidic pH, the amino acid side chain charge neutralization of acidic residues, especially GLU64, promotes the formation of additional favorable interactions between the silk fibroin and the drug. The SFN-2 also possess a good aerosol property with a mass median aerodynamic diameter of 3.82 ± 0.71 μm and fine particle fraction of 64.0 ± 1.4%. These SFN-2 particles were selectively endocytosed by macrophages through clathrin- and caveolae-mediated endocytosis with a higher uptake efficiency (66.2 ± 2.1%) and were found to exhibit a sustained drug release in the presence of macrophage intracellular lysates. The cytokine and biomarker expression analyses revealed that SFN-2 could exhibit an immunomodulatory effect by polarizing the macrophages to an initial M1 phase and later M2 phase. Further, R-SFN-2 also exhibited an enhanced and sustained intracellular antibacterial activity against Mycobacterium smegmatis-infected macrophages than free rifampicin. Thus, the self-assembled silk fibroin particles with immunomodulatory action combined with a good aerosol and intracellular drug release property can be an attractive choice as a carrier for developing pulmonary drug delivery systems.

Chronic wounds require suitable treatment and management strategies for proper healing. Among other causes, infection delays the healing of wounds and increases the risk of wound-related complications. In this study, an inherently antibacterial and biocompatible wound dressing is developed to enhance the healing. Chemical modification of a natural polysaccharide, Isabgol with epoxypropyltrimethylammonium chloride, renders antibacterial activity to the material. This is the first report of such chemical modification of this polymer for biomedical applications. The modified material is freeze-dried to obtain porous scaffolds. 13C NMR and FTIR analysis confirmed the modification of the Isabgol polymer chains with EPTMAC. SEM analysis confirmed the porous structure of the scaffold that would allow the exchange of gases and nutrients through the matrix. The material can swell up to 17 times its initial weight, allowing it to absorb wound exudates and maintain a moist environment at the wound site. Thermogravimetric analysis and compression testing showed that the scaffold has suitable thermal and mechanical properties. The material is antibacterial and can potentially prevent infections at the wound site. In vitro studies have confirmed that these scaffolds are cytocompatible and hemocompatible. These properties indicate that the EPTMAC-modified Isabgol scaffolds would be suitable for wound dressing applications.