Physical-Chemical Characterizations of Synthetic Dual Niosomes for Antibacterial Delivery of Lysostaphin and LL-37.

Sadeghi, Somayeh; Bakhshandeh, Haleh; Cohan, Reza Ahangari; Ehsani, Parastoo; Norouzian, Dariush

Non-ionic surfactant vesicles known as niosomes are synthetic vesicles with numerous pharmaceutical applications. In this study, a unique combination of two antibacterial macromolecules, lysostaphin protein and LL-37 peptide, was prepared in a nanoniosomal delivery system to evaluate the physicochemical properties of prepared niosomes and the possible synergistic interactions of niosomal drugs. Two different niosomal formulations of lysostaphin and LL-37 were prepared using a thin film hydration method and analyzed in terms of size, shape, entrapment efficiency, and FTIR spectroscopy. The stability of niosomes was evaluated at 4, 25, and 37°C. Also, the antibacterial activity of LL-37 as a single drug or in combination with lysostaphin was evaluated in free and encapsulated forms against E. coli and A. baumannii for 72 h using time kill assay. The optimal niosomal formulation was obtained by mixing surfactants (Span 60 and Tween 60; 2:1 w/w) and cholesterol at a ratio of 1:1 (w/w). Mean diameters of lysostaphin and LL-37 in optimal formulation were 508.50 and 292.65 nm respectively. This formulation showed spherical well-dispersed niosomes with high entrapment efficiency and had good stability at 4°C for 2 months. Furthermore, no chemical bond was formed between the niosomal membrane and lysostaphin or LL-37, according to FTIR analysis. Finally, a prolonged antibacterial activity of dual-drug-loaded niosomes was observed compared with their free form. The finding indicated that lysostaphin/LL-37 in a niosomal nanocarrier offers a delivery system with promising physicochemical properties for long-term protection against human chronic infections caused by Gram-negative bacteria.

ESCHERICHIA coli; NONIONIC surfactants; FOURIER transform infrared spectroscopy; DRUG interactions; PEPTIDES; CHEMICAL bonds; MACROMOLECULES

Pharmaceutical Chemistry Journal, 2023, Vol 57, Issue 9, p1418

0091-150X

Academic Journal

10.1007/s11094-023-03005-w