Drug Targeting of Inflammatory Bowel Diseases by Biomolecules

Abstract

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn’s disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient’s susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD’s societal impact.

Nanoparticles for oral delivery: targeted therapy for inflammatory bowel disease

“…73 In addition, polymeric NPs can encapsulate various drug agents including biologics, smallmolecule drugs, small interfering RNA, and DNA. 74,75 Additionally, polymeric NPs can conjugate targeted ligands such as antibodies, peptides, or small molecules specifically binding tissue components or cellular receptors. [76][77][78][79] Recently, various biodegradable polymeric NPs including poly(lactide-co-glycolide) (PLGA), chitosan, dendrimer, and gelatin have been utilized (Fig.…”

Roles of Gut Bacteriophages in the Pathogenesis and Treatment of Inflammatory Bowel Disease

“…mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine) (Moja et al, 2015;Wang et al, 2016;Matsumoto et al, 2016;Bots et al, 2018;Sokollik et al, 2018;Damiao et al, 2019;Nielsen et al, 2020;Antunes et al, 2021). Although these therapies have been proved effective in IBD patients, severe adverse events with impaired quality of life can't be ignored (Quezada et al, 2018).…”

“…Due to the relapsing inflammatory disorders in IBD patients, controlling of intestinal inflammatory is the primary target of treatment. Currently, traditional therapies includes 5-aminosalicylic acid derivatives (e.g., sulfasalazine and mesalazine), corticosteroides (e.g., prednisone, hydrocortisone, budesonide, prednisolone, dexamethasone) and immunosuppressive agents (e.g., azathioprine, methotrexate, mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine) ( Moja et al., 2015 ; Wang et al., 2016 ; Matsumoto et al., 2016 ; Bots et al., 2018 ; Sokollik et al., 2018 ; Damiao et al., 2019 ; Nielsen et al., 2020 ; Antunes et al., 2021 ). Although these therapies have been proved effective in IBD patients, severe adverse events with impaired quality of life can’t be ignored ( Quezada et al., 2018 ).…”

Budesonide-Loaded Hyaluronic Acid Nanoparticles for Targeted Delivery to the Inflamed Intestinal Mucosa in a Rodent Model of Colitis

“…Various delivery systems for colon-targeted therapy have been developed; however, there are several controversies in clinical efficacy of these systems due to inter-individual variations and pathologic conditions in IBD [11][12][13]. Therefore, development of novel drug delivery system (DDS) for specific targeted delivery of BDS to the inflamed area has the benefit of enhanced therapeutic efficacy while maintaining a good safety profile [14][15][16].…”