Nanoparticle-Based Oral Drug Delivery Systems Targeting the Colon for Treatment of Ulcerative Colitis

摘要

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic relapsing inflammation of the gastrointestinal tract. Delivery of orally administered drugs to the colon is highly desirable for the treatment of UC, as it improves their efficacy while reducing systemic toxicity. However, the targeting of oral drugs to the colon, which is located at the distal end of the gastrointestinal tract, is difficult due to physiological challenges, biochemical barriers, and environmental barriers, including those associated with mucus and epithelium. Recent preclinical studies have indicated that nanoparticle-based drug delivery systems (DDS) may be promising tools for targeted delivery to the colon, with potentially effective outcomes in the treatment of UC. This review highlights general considerations and limitations for oral drug delivery to the colon. Further, this review provides a systematic evaluation of synthetic nanoparticle-based DDS, and emerging naturally derived nanoparticles (eg, extracellular vesicles and plant-derived nanoparticles). These novel nanoparticle-based treatment strategies for UC may offer the opportunity for the practical translation of nanoparticle formulas into the clinic. class="kwd-title">Keywords: IBD therapy, ulcerative colitis, nanoparticles, oral drug delivery systems class="head no_bottom_margin" id="s1title">INTRODUCTIONInflammatory bowel disease (IBD) is a group of chronic relapsing disorders of the gastrointestinal (GI) tract that are characterized pathologically by intestinal inflammation and epithelial injury. Crohn’s disease (CD) and ulcerative colitis (UC) are the 2 major types of IBD. CD affects the entire length of the GI tract, from the oral mucosa to the anus, with the terminal ileum being the most affected part in 90% of patients. UC characteristically involves only the large bowel; it begins in the rectum and progressively extends to the proximal colon, and some patients with severe disease experience a tropism for the appendix.To date, the etiology of IBD is not completely understood. Conventional medication for IBD therapy comprises anti-inflammatory drugs (eg, 5-aminosalicyclic acid and corticosteroids) and immunosuppressive agents (eg, azathioprine, 6-mercaptopurine, methothexate, ciclosporin-A and tacrolimus). The emergence of monoclonal antibodies as biological therapies has significantly increased the treatment options for IBD in recent years. In 1998, the tumor necrosis factor (TNF)–α antibody inflixmab was the first biological to be approved by the US Food and Drug Administration (FDA) for the therapy of severe, active, and fistulizing CD. Since then, further TNF-α antibodies for IBD treatment, such as adalimumab or certolizumab, have made it to the market, with more still in the development pipelines. In addition, other antibodies such as ustekinumab and natalizumab targeting IL-12/IL-23 and adhesion molecules also have been suggested as therapeutic options in IBD (). However, there is still a large unmet need for novel therapeutic approaches as many patients do not respond to the clinically approved drugs, including TNF blockers and vedolizumab.>TABLE 1:Monoclonal Antibody–Based Biological Therapies for IBD