Nanoemulsions Embedded in Alginate Beads as Bioadhesive Nanocomposites for Intestinal Delivery of the Anti-Inflammatory Drug Tofacitinib.

Oral administration of nanoparticles (NPs) is a promising strategy to overcome solubility and stability issues of many active compounds. However, this route faces major obstacles related to the hostile gastrointestinal (GI) environment, which impairs the efficacy of orally administered nanomedicines. Here, we propose nanocomposites as a promising approach to increase the retention time of NPs in the intestinal tract by using bio- and mucoadhesive matrixes able to protect the cargo until it reaches the targeted area. A microfluidic-based approach has been applied for the production of tailored nanoemulsions (NEs) of about 110 nm, used for the encapsulation of small hydrophobic drugs such as the anti-inflammatory JAK-inhibitor tofacitinib. These NEs proved to be efficiently internalized into a mucus-secreting human intestinal monolayer of Caco-2/HT29-MTX cells and to deliver tofacitinib to subepithelial human THP-1 macrophage-like cells, reducing their inflammatory response. NEs were then successfully encapsulated into alginate hydrogel microbeads of around 300 µm, which were characterized by rheological experiments and dried to create a long-term stable system for pharmaceutical applications. Finally, ex vivo experiments on excised segments of rats' intestine proved the bioadhesive ability of NEs embedded in alginate hydrogels compared to free NEs, showing the advantage that this hybrid system can offer for the treatment of intestinal pathologies.

In vitro efficacy of newly designed vancomycin-based microparticles.

PURPOSE: To compare the in vitro bactericidal and anti-adhesion properties of vancomycin-based microparticles and lyophilized vancomycin and estimate their relevance to perioperative antibiotic prophylaxis and endophthalmitis prevention. SETTING: University research laboratory, Lyon, France. METHODS: The bactericidal and anti-adhesion properties of a newly designed drug-delivery system were assessed on Staphylococcus epidermidis clinical strain N890074 containing the intercellular adhesion locus ica. Lyophilized vancomycin at 20 mug/mL was used as a standard. The new drug-delivery system, designed for the study, consisted of sterile, biocompatible, and biodegradable microparticles with continuous release of vancomycin. To obtain bacterial killing and anti-adhesion curves, experiments were first performed in a bacterial suspension containing 1000 colony-forming units per milliliter. Experiments were then performed with intraocular lenses incubated in the suspension. Efficacy was investigated by bacterial counts and scanning electron microscopy observations. RESULTS: The bactericidal and anti-adhesion effects of vancomycin-based microparticles started after 3 hours (P<.002) and 1 hour (P<.001), respectively, and of lyophilized vancomycin, after 1 hour (P = .004) and 1 hour (P<.001), respectively. There was no difference between the 2 forms of vancomycin in the bactericidal effect starting at 21 hours and the anti-adhesion effect starting at 6 hours (P>.05). CONCLUSIONS: The newly designed vancomycin-based microparticles showed relevant antibacterial and anti-adhesion properties after releasing a sufficient antibacterial quantity, proving that vancomycin remains efficient after undergoing the encapsulation process.