RESUMEN

Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, the present study aims to develop a dual-targeted delivery system with a nanoparticle-in-microparticle (nano-in-micro) structure. The prepared Asiatic Acid-loaded delivery system (AA/CDM-BT-ALG) has pH-sensitive properties. Cellular uptake evaluation confirms that nanoparticles exhibit targeted absorption by macrophages and Caco-2 cells through mannose (Man) receptor and biotin-mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicates that the colon of the microspheres group shows higher fluorescence intensity with longer duration than the other groups. This finding indicates that the microspheres exhibit selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM-BT-ALG significantly alleviates the histopathological characteristics of the colon, reduced neutrophil, and macrophage infiltration, and decreases pro-inflammatory cytokine expression. Furthermore, the effect of AA/CDM-BT-ALG on colitis is validated to be closely related to the TLR4/MyD88/NF-κB signaling pathway. The present findings suggest that the development of a dual-targeted delivery system is accomplished effectively, with the potential to serve as a drug-controlled release system for treating UC.

Asunto(s)

Colitis Ulcerosa , Colitis , Nanopartículas , Ratones , Humanos , Animales , Colitis Ulcerosa/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Células CACO-2 , Distribución Tisular , Colitis/tratamiento farmacológico , Colon/metabolismo , Colon/patología , Nanopartículas/química , Modelos Animales de Enfermedad

RESUMEN

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.

Asunto(s)

Alginatos/química , Quitosano/análogos & derivados , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/administración & dosificación , Nanopartículas/química , Administración Oral , Animales , Quitosano/química , Colitis/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Femenino , Células HT29 , Humanos , Inflamación/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Infliximab/química , Mucosa Intestinal/metabolismo , Ratones , Ratones Endogámicos C57BL , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Full visible spectrum photonic droplets and consequent microcapsules with nano-in-micro structure were prepared through microfluidic technique. Photo-curable resin and suspension of monodispersed soft nanogels were used as shell and core of the microcapsules, respectively. Upon UV irradiation, the droplets can be subsequently transformed into photonic microcapsules with an ultrathin polymeric shell. The shell thickness of the photonic microcapsules was found to be approximately 700 nm. Due to the ultrathin shell and soft core, the photonic microcapsules with nano-in-micro structure display dramatic changes both in shapes and photonic property under the impact of osmosis effect or temperature stimulus. Typically, the shell and core parts of nano-in-micro structure could respectively undergo a size expansion/even rupture and a size decrease/buckling under hypotonic and hypertonic condition. Correspondingly, the peak value of the reflection spectra of the microcapsules showed a redshift and blue shift, respectively. The mechanism to the structure and optical properties variation involves the osmotic pressure induced the volume-fraction change of the nanogel-based photonic dispersion and the shell buckling of the core/shell microcapsules.