DEAE-chitosan nanoparticles as a pneumococcus-biomimetic material for the development of antipneumococcal therapeutics

• Published in: Carbohydrate polymers 2021-12, Vol.273, p.118605-118605, Article 118605
• Main Authors: Vázquez, Roberto, Caro-León, Francisco J., Nakal, Alberto, Ruiz, Susana, Doñoro, Carmen, García-Fernández, Luis, Vázquez-Lasa, Blanca, San Román, Julio, Sanz, Jesús, García, Pedro, Aguilar, María Rosa
• Format: Article
• Language: English
• Subjects: A549 Cells; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Bacterial Proteins - metabolism; Biomimetic Materials - chemistry; Biomimetic Materials - metabolism; Chitosan; Chitosan - analogs & derivatives; Chitosan - chemistry; Chitosan - metabolism; Diethylaminoethyl; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug Liberation; Endopeptidases - chemistry; Endopeptidases - pharmacology; Enzybiotics; Humans; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Pneumococcus; Streptococcus pneumoniae - drug effects
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2021.118605

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts. [Display omitted] •Nanoparticles of chitosan derivatized with dimethylaminoethyl were synthesized (ChiDENPs).•ChiDENPs mimic pneumococcal cell wall ability to bind choline-binding proteins (CBPs).•CBPs binding capacity of ChiDENPs has been exploited to encapsulate the enzybiotic Cpl-711.•Cpl-711 was released in 2–3 h, providing a relatively long therapeutic window.