title: Poly-L-lysine-coated albumin nanoparticles: stability, mechanism for increasing in vitro enzymatic resilience, and siRNA release characteristics.
abstract: Enzymatic degradation of nanoparticle (NP)-based drug delivery vehicles is a major factor influencing the administration routes as well as the site-specific delivery of NPs. To understand the stability of albumin NPs in an aggressive proteolytic environment, bovine serum albumin (BSA) NPs were fabricated via a coacervation technique and stabilized by coating using different molecular weights (MWs: 0.9-24 kDa) and concentrations (0.1-1.0 mg ml(-1)) of the cationic polymer, poly-L-lysine (PLL). A short interfering ribonucleic acid (siRNA) was used as a model drug for encapsulation in the BSA NPs. The generated NPs were characterized for morphology (with atomic force microscopy), size (with photon correlation spectroscopy) and charge (zeta-potential). The size range of formed BSA particles (155 ± 11 to 3800 ± 1600 nm) was effectively controlled by the MW and concentration of the PLL used for coating. The aqueous solution stability of NPs increased with an increasing MW and PLL concentration. However, in the presence of trypsin, NPs coated with higher MW PLL were not as stable as those formed using lower MW PLL. This trend was also confirmed based on the release pattern of siRNA in the presence of trypsin. We conclude that, when designing stabilizing coatings for soft protein-based NPs, smaller molecules may be more suitable for particle coating if enhanced proteolytic resistance and more stable NPs are desired for targeted drug delivery applications.
authors.affiliation: Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta T6G2G6, Canada.
authors.forename: Harsh Deep
authors.initials: HD
authors.lastname: Singh
authors.forename: Guilin
authors.initials: G
authors.lastname: Wang
authors.forename: Hasan
authors.initials: H
authors.lastname: Uludağ
authors.forename: Larry D
authors.initials: LD
authors.lastname: Unsworth
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011107:Polylysine / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C039217:fluorescein isothiocyanate bovine serum albumin; D011107:Polylysine; D012710:Serum Albumin, Bovine; D014357:Trypsin; D016650:Fluorescein-5-isothiocyanate