Vancomycin-Loaded Nanoparticles Enhance Sporicidal and Antibacterial Efficacy for Clostridium difficile Infection

Abstract

Current antibiotic treatments fail to eliminate the Clostridium difficile ( C. difficile ) spores and induce dysbiosis and intestinal inflammation via off-target effect, which causes refractory C. difficile infection raise an unmet need for a spore-specific antimicrobial treatment. We developed a sporicidal and antimicrobial vancomycin-loaded spore-targeting iron oxide nanoparticle (van-IONP) that selectively binds to C. difficile spores. Cryo-electron microscopy showed that vancomycin-loaded nanoparticles can target and completely cover spore surfaces. They not only successfully delayed the germination of the spores but also inhibited ∼50% of vegetative cell outgrowth after 48 h of incubation. The van-IONPs also inhibited the interaction of spores with HT-29 intestinal mucosal cells in vitro . In a murine model of C. difficile infection, the van-IONP significantly protected the mice from infected by C. difficile infection, reducing intestinal inflammation, and facilitated superior mucosal viability compared with equal doses of free vancomycin. This dual-function targeted delivery therapy showed advantages over traditional therapeutics in treating C. difficile infection.

Novel Colloidal Nanocarrier of Cetylpyridinium Chloride: Antifungal Activities on Candida Species and Cytotoxic Potential on Murine Fibroblasts

“…Iron oxide nanoparticles (IONPs) have also been used in several biomedical applications (e.g., drug delivery, tissue engineering, contrast agents) due to their nano-sized and magnetic properties [ 22 , 23 ]. Literature data show that IONPs-based nanocarriers were able to improve the physico-chemical properties of the aggregated drugs and to combat yeasts, bacteria and spores [ 24 , 25 , 26 , 27 , 28 , 29 ]. Moreover, in order to avoid the aggregation of IONPs and to increase their biocompatibility, coatings with natural polymers such as chitosan (CS) have been adopted in the nanocarrier engineering, forming associations known as core-shell [ 30 , 31 ].…”

NPs-TiO2 and Lincomycin Coexposure Induces DNA Damage in Cultured Human Amniotic Cells

“…This effect is also used in medicine to deliver drugs to target organs. In fact, one approach for increasing the antimicrobial efficacy of antibiotics, without raising the overall dose, is to increase the local targeting concentration by conjugating antibiotics with nanoparticles [41,42]. So, the application of nanoparticles has emerged as an option in the control of bacterial infections in many drugs, that present titanium dioxide as a coloring additive of the capsule, such as lincomycin.…”

Nanobiosystems for Antimicrobial Drug-Resistant Infections

“…They also inhibited the interaction of spores with HT-29 intestinal mucosal cells in vitro. In vivo (in a murine model), the IONPs significantly protected mice from C. difficile compared to free VAN (reducted intestinal inflammation and superior mucosal viability were demonstrated) [ 128 ]. In another in vitro study, metronidazole-loaded particles were prepared and coated with chitosan for increased mucoadhesive properties.…”