Millions of individuals worldwide have been affected with Inflammatory bowel disease (IBD), a chronic gastrointestinal tract inflammation. Although several therapeutics are available for IBD, they only selectively target areas of inflammation. Therefore, the main cause of the disease remains untreated. Several nanotechnology-based strategies have been formulated to treat extreme gastric conditions.
Study: Emerging Nanotechnologies and Microbiome Engineering for the Treatment of Inflammatory Bowel Disease. Image Credit: Panchenko Vladimir/Shutterstock.com
Nano-based drugs can effectively target inflamed regions via an active or passive approach. A new review has been recently accepted for publication in Molecular Pharmaceutics that focuses on recent advancements in nanotechnology-based treatments for IBD, mainly, targeting inflammation and dysregulated gut microbiomes.
Common Symptoms of Inflammatory Bowel Disease
Scientists worldwide have been working on developing effective treatments for IBD, which has resulted in a huge amount of literature associated with the disease. Two main forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD), which occur due to chronic inflammation of the gastrointestinal (GI) tract.
Although both UC and CD manifest similar symptoms, they are associated with different pathological and clinical factors. Some common symptoms of both diseases are loss of appetite, fatigue, cramping, and abdominal pain. Genomic studies related to IBD revealed that 162 genes are involved with this disease, among which 110 are common for both UC and CD.
IBD patients often undergo periods of illness and remission, with varied symptoms and severity. Typically, CD is linked with small bowel disease, and granulomas, while UC can present with rectal inflammation and antineutrophil cytoplasmic antibodies.
Previous studies have shown that IBD can occur due to dysregulated gut microbiome. Disturbances in the gut microbiome occur because of many reasons, including an uncontrolled bacterial proliferation of pathobionts and barrier infiltration.
Nanotechnology-based Therapeutics for Inflammatory Bowel Disease
As the number of IBD cases is continually growing globally, there is an urgent need for effective therapeutics against IBD. To date, the precise pathogenesis of IBD remains unclear; however, scientists are exploring if a particular microbe can cause the disease. Currently, IBD patients are treated with anti-inflammatory drugs, which suppress symptoms caused by immune responses. Additionally, monoclonal antibody therapies targeting inflammatory cytokines are used to treat moderate to severe IBD symptoms.
Advancements in nanotechnology have resulted in developing several therapeutics that are effective against harmful diseases. Nanoparticles (NPs) exhibited high drug loading capability, efficiently delivering active compounds at the targeted site. Scientists have developed mice models to study the efficacy of the newly developed therapeutics against IBD.
Researchers utilized natural polyphenols, such as tannic acid and catechin, to synthesize self-assembled nanoparticles, which are considered to be Generally Recognized as Safe (GRAS) compounds by the U.S. Food and Drug Administration (FDA). These polyphenols contain antioxidative properties with radical-scavenging activities that have been previously applied for IBD treatment.
Recently, polymers were paired with polyphenol and were assembled into nanoparticles, known as PPNP. PPNP loaded with dexamethasone (DEX), was reported to be highly effective against colitis. Another approach related to decreasing reactive oxidant species (ROS) is by mimicking the host’s natural enzyme, superoxide dismutase (SOD). This enzyme converts superoxide into hydrogen peroxide, which in turn becomes hydroxyl radical via reduction. The 1,2- distearoyl-sn-glycero-3-phosphoethanolamine (DSPE)-polyethylene glycol (PEG) was self-assembled into nanoparticles and was found to be stable in the GI tract. This nanosystem released tempol, i.e., radical scavenger SOD, at the inflammation site and could effectively deliver the drug to the inflamed colon.
Nanoparticles to Rectify Gut Microbiome Imbalance Due to IBD
Several studies have shown that the development and progression of IBD in patients are linked with their gut microbiome imbalance. Compared to healthy individuals, IBD patients possess differential gut microbiota. Recently, the fecal microbiota transplantation (FMT) strategy has been developed to improve the gut microbiome of IBD patients. However, this procedure comes with major limitations associated with biosafety. Another simplistic method that has improved IBD patients' gut microbiome is increased intake of probiotics.
Recently, scientists have engineered nanoparticles to modulate the gut microbiota to improve IBD conditions. Additionally, these newly synthesized nanoparticles could effectively reduce inflammation associated with colorectal cancer. Researchers designed hyaluronic acid-bilirubin treatment, which is known as HABN, as a potential IBD therapy that can reduce inflammation as well as modulate the gut microbiome. The chemical conjugation between hyaluronic acid (HA) and bilirubin (BR) enabled the development of self-assembled nanoparticles that could be orally administered.
Researchers have also developed colon-retentive hydrogel, containing anti-PD-1, which leads to modulation of the gut microbiome. This therapy substantially increases the abundance of Lactobacillus, Akkermansia, and Roseburia, major producers of short-chain fatty acids (SCFA), which reduces the risks of IBD. Combined with inulin gel consumption, the treatment was found to be effective against colorectal cancer in mice models.
The future of nanotechnology-based therapy against IBD is extremely promising. Pharmaceutical companies are focussing on maintaining the size of nanoparticles used for IBD treatment, as it affects the pharmacodynamics and pharmacokinetics of the drugs. More research is required to better understand the effect of nanoparticles on the gut microbiome, which could substantially improve IBD patients’ outcomes.
Abed, A.O. et al. (2022) Emerging Nanotechnologies and Microbiome Engineering for the Treatment of Inflammatory Bowel Disease. Molecular Pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.2c00222