Mesoporous silica microparticles gated with a bulky azo derivative for the controlled release of dyes/drugs in colon

Abstract

Mesoporous silica microparticles were prepared, loaded with the dye safranin O (M-Saf) or with the drug budesonide (M-Bud) and capped by the grafting of a bulky azo derivative. Cargo release from M-Saf at different pH values (mimicking those found in the gastrointestinal tract) in the absence or presence of sodium dithionite (a reducing agent mimicking azoreductase enzyme present in the colon) was tested. Negligible safranin O release was observed at pH 6.8 and 4.5, whereas a moderate delivery at pH 1.2 was noted and attributed to the hydrolysis of the urea bond that linked the azo derivative onto the external surface of the inorganic scaffold. Moreover, a marked release was observed when sodium dithionite was present and was ascribed to the rupture of the azo bond in the molecular gate. Budesonide release from M-Bud in the presence of sodium dithionite was also assessed by ultraviolet-visible spectroscopy and high performance liquid chromatography measurements. In addition, preliminary in vivo experiments with M-Saf carried out in mice indicated that the chemical integrity of the microparticles remained unaltered in the stomach and the small intestine, and safranin O seemed to be released in the colon.

Curcumin Nanocrystal/pH-Responsive Polyelectrolyte Multilayer Core–Shell Nanoparticles for Inflammation-Targeted Alleviation of Ulcerative Colitis

“…Ulcerative colitis (UC) is a chronic, recurrent inflammatory disease of the innermost lining of the colon and rectum. , Delivery of orally administered drugs to the colon is highly desirable in UC therapy, as it can result in low systemic toxicity and high efficacy of the drug. , However, delivery of the drugs to the colon is challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT), such as degradation of the drug in acidic pH conditions prevalent in the lumen, presence of digestive enzymes, and physical adsorption by the mucosa. , To address these issues, various types of nanocarrier-based drug delivery systems, such as polymeric nanoparticles, , lipid nanoparticles, silica nanoparticles, liposomes, , nanoparticles in microparticles, and nanogels, have been developed. However, low drug loading capacity and excipient-associated side effects are intrinsic limitations associated with these drug delivery systems.…”

Mesoporous silica nanostructure modified with azo gatekeepers for colon targeted delivery of 5‐fluorouracil

“…42 Sodium dithionate is a reducing agent and acts as a mimicker of azoreductases. 42 Following this strategy herein, our synthesized MS@5-Fu was gated by an azobenzene derivative. The success of the synthetic strategy was proved by FT-IR and BJH data, which showed that pores were well blocked.…”

“…These enzymes could be involved in the biotransformation and detoxification of compounds containing azo groups, like azoic drugs, dyes, and nitro‐bearing aromatics, by reduction of the azo bond 41 . By this means, azo‐capped magnetic mesoporous silica was explored for the controlled release of safranin O as a dye 21 and budesonide as a corticosteroid used for ulcerative colitis 42 . Sodium dithionate is a reducing agent and acts as a mimicker of azoreductases 42 …”

“…41 By this means, azo-capped magnetic mesoporous silica was explored for the controlled release of safranin O as a dye 21 and budesonide as a corticosteroid used for ulcerative colitis. 42 Sodium dithionate is a reducing agent and acts as a mimicker of azoreductases. 42 Following this strategy herein, our synthesized MS@5-Fu was gated by an azobenzene derivative.…”

Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment

“… [ 39 ] UC Passive Azoreductase enzymes – Ornidazole and sulfasalazine Sulfasalazine-polyethylene glycol micelles HEK 293 cell line model The excellent stability nanomicelles release the loaded drug by being activated by azo reductase. [ 40 ] UC Passive Azoreductase triggered Oral delivery M-Saf M-Bud MSMs Mice model Capable of delivering drugs to targeted colonic sites [ 41 ] UC Passive α-amylase responsive Oral delivery Dex HES-CUR NPs DSS mice model The excellent anti-inflammatory and antioxidant properties of NPs enable multi-drug combination therapy. [ 42 ] UC Passive ROS-responsive Oral delivery Bud and Tpl Bud-ATK-Tpl DSS mice model and RAW264.7 cell line model High drug release to minimize adverse effects; colitis treatment that combines anti-inflammatory and antioxidant treatment.…”