Spray-dried pH-sensitive chitosan microparticles loaded with Mycobacterium bovis BCG intended for supporting treatment of Helicobacter pylori infection

Abstract

Gram-negative spiral-shaped Helicobacter pylori (Hp) bacteria induce the development of different gastric disorders. The growing resistance of Hp to antibiotics prompts to search for new therapeutic formulations. A promising candidate is Mycobacterium bovis BCG (BCG) with immunomodulatory properties. Biodegradable mucoadhesive chitosan is a good carrier for delivering BCG mycobacteria to the gastric mucosal environment. This study aimed to show whether BCG bacilli are able to increase the phagocytic activity of Cavia porcellus—guinea pig macrophages derived from the bone marrow towards fluorescently labeled Escherichia coli. Furthermore, to encapsulate live BCG bacilli, in spray-dried chitosan microparticles (CHI-MPs), and assess the pH-dependent release of mycobacteria in pH conditions mimicking gastric (acidic) or gut (alkaline) milieu. Microparticles (MPs) were made of chitosan and coated with Pluronic F-127-(Plur) or N-Acetyl-d-Glucosamine-(GlcNAc) to increase the MPs resistance to low pH or to increase anti-Hp effect, respectively. Spray-drying method was used for microencapsulation of live BCG. The biosafety of tested CHI-MPs has been confirmed using cell models in vitro and the model of guinea pig in vivo. The CHI-MPs loaded with BCG released live mycobacteria at pH 3.0 (CHI-GlcNAc-MPs) or pH 8.0. (CHI-Plur-MPs). The CHI-MPs loaded with live BCG can be used for per os inoculation of Cavia porcellus to check the effectiveness of delivered mycobacteria in increasing anti-H. pylori host response.

Polymeric pH-Responsive Metal-Supramolecular Nanoparticles for Synergistic Chemo-Photothermal Therapy

“…The contemporary conceptualization of stimulus-response systems as “intelligent” has been extensively scrutinized and holds vast potential for biomedical applications. − These systems are designed to release their payloads in reaction to external stimuli, such as pH, − temperature, , light exposure, ,− ionic strength, , chemicals, enzymes, etc. The pH-response feature, due to the extracellular pH of most cancer tissues (pH = 5.7–7.8) being lower than that of normal tissues and blood, and pH decreases further within the cell, especially within endosomal (pH = 5.5–6.0) and lysosomal (pH = 4.5–5.0) compartments, has been particularly intriguing.…”