4.7 Review

How could nanobiotechnology improve treatment outcomes of anti-TNF-α therapy in inflammatory bowel disease? Current knowledge, future directions

Journal

JOURNAL OF NANOBIOTECHNOLOGY
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12951-021-01090-1

Keywords

Anti-TNF-alpha antibodies therapy; Inflammatory bowel diseases; Lipid nanoparticles; Oral drug delivery

Funding

  1. Portuguese Science and Technology Foundation (FCT/MCT)
  2. European Funds (PRODUCER/COMPETE)-project [UIDB/04469/2020]
  3. FEDER, under the Partnership Agreement PT2020
  4. National Science Centre within the MINIATURA 4 for a single research activity [2020/04/X/ST5/00789]
  5. START 2021 Program of the Foundation for Polish Science (FNP)

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Despite significant advancements in the treatment of inflammatory bowel disease in recent years, there is still a large room for improvement. Oral anti-TNF-alpha antibody therapy is hypothesized to provide targeted anti-inflammatory effects without significant systemic exposure, potentially improving long-term treatment outcomes and safety. Various attempts have been made to design oral formulations of these molecules, aiming to enter a new era of treatment for IBD.
Despite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-alpha) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-alpha blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-alpha antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-alpha therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-alpha antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.

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