Mucoadhesive and mucopenetrating chitosan nanoparticles for glycopeptide antibiotic administration

• Published in: International journal of pharmaceutics Vol. 606; p. 120874
• Main Authors: Abruzzo, A., Giordani, B., Miti, A., Vitali, B., Zuccheri, G., Cerchiara, T., Luppi, B., Bigucci, F.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.09.2021
• Subjects: Antibacterial activity; Chitosan nanoparticles; Mucoadhesion; Mucopenetration; Vancomycin; Antibacterial activity; Mucopenetration; Chitosan nanoparticles; Vancomycin; Mucoadhesion
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2021.120874

[Display omitted] •Chitosan based nanoparticles (NPs) were prepared for vamcomycin (VM) delivery.•The selection of a suitable crosslinker allowed to modulate NP properties.•Chitosan/sodium tripolyphosphate NPs showed the best mucoadhesive ability.•Sodium carboxymethylcellulose and phytic acid provided the best mucopenetrating NPs.•NPs maintained VM antimicrobial activity against Gram-positive bacterial species. The use of nanoparticles (NPs) represents a useful strategy for peptide antibiotic delivery to mucosal membranes by either prolonging drug residence time at the target site (mucoadhesive NPs) or by enhancing diffusion across mucus layer to reach the underlying epithelium (mucopenetrating NPs). The purpose of this study was to design chitosan (CH) NPs and to evaluate their employment as mucoadhesive and/or mucopenetrating systems for vancomycin (VM) delivery. NPs were prepared by ionic gelation of CH with sodium carboxymethylcellulose (CMC), sodium alginate (ALG), sodium tripolyphosphate (TPP) or phytic acid (PA) and characterized in terms of size, zeta-potential, morphology, drug encapsulation efficiency, mucoadhesion and mucopenetrating ability. Moreover, in vitro tests were conducted to evaluate VM release and the antibacterial activity against Staphylococcus aureus and Bacillus subtilis. NPs showed sizes ranged from 150 nm to 350 nm with good polydispersity index and positive zeta-potential. The selection of the suitable crosslinker allowed to modulate the mucoadhesive/mucopenetrating properties: CH/TPP NPs showed the best mucoadhesive ability, while CH/PA and CH/CMC NPs were characterized by an improved diffusion across the mucus layer. Further, NPs allowed a fast and complete release of VM, maintaining the antibacterial activity against the tested bacteria species.