open access publication

Article, 2024

Tailored Polymersomes for Enhanced Oral Drug Delivery: pH‐Sensitive Systems for Intestinal Delivery of Immunosuppressants

Small, ISSN 1613-6829, 1613-6810, Page e2403640, 10.1002/smll.202403640

Contributors

Tollemeto, Matteo 0000-0002-6220-2877 (Corresponding author) [1] Ursulska, Sintija [1] Welzen, Pascal L W 0000-0003-3998-1742 [2] Thamdrup, Lasse Højlund Eklund 0000-0002-9498-1529 [1] Malakpour-Permlid, Atena [1] Li, Yudong 0009-0006-9140-5733 [2] Soufi, Gohar [1] Padial, Tania Patiño [2] Christensen, Jørn Bolstad 0000-0002-7641-8302 [3] Nielsen, Line Hagner 0000-0002-3789-4816 [1] Van Hest, Jan C M 0000-0001-7973-2404 [2] Boisen, Anja [1]

Affiliations

  1. [1] Technical University of Denmark
    2. [NORA names: DTU Technical University of Denmark; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] Eindhoven University of Technology
    3. [NORA names: Netherlands; Europe, EU; OECD];
  3. [3] University of Copenhagen
    4. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]

Abstract

Ensuring precise drug release at target sites is crucial for effective treatment. Here, pH-responsive nanoparticles for oral administration of mycophenolate mofetil, an alternative therapy for patients with inflammatory bowel disease unresponsive to conventional treatments is developed. However, its oral administration presents challenges due to its low solubility in the small intestine and high solubility and absorption in the stomach. Therefore, this aim is to design a drug delivery system capable of maintaining drug solubility compared to the free drug while delaying absorption from the stomach to the intestine. Successful synthesis and assembly of a block copolymer incorporating a pH-responsive functional group is achieved. Dynamic light scattering indicated a significant change in hydrodynamic size when the pH exceeded 6.5, confirming successful incorporation of the pH-responsive group. Encapsulation and controlled release of mycophenolate mofetil are efficiently demonstrated, with 90% release observed at intestinal pH. In vitro cell culture studies confirmed biocompatibility, showing no toxicity or adverse effects on Caco-2 cells. In vivo oral rat studies indicated reduced drug absorption in the stomach and enhanced absorption in the small intestine with the developed formulation. This research presents a promising drug delivery system with potential applications in the treatment of inflammatory bowel disease.

Keywords

Caco-2, Caco-2 cells, absorption, administration, administration of mycophenolate mofetil, adverse effects, alternative therapies, applications, assembly, biocompatibility, block, block copolymers, bowel disease, cell culture studies, cells, controlled release, conventional treatment, copolymers, cultural studies, delayed absorption, delivery, delivery of immunosuppressants, delivery system, disease, drug, drug absorption, drug delivery, drug delivery systems, drug release, drug solubility, dynamic light scattering, effect, effective treatment, encapsulation, enhanced absorption, enhancing oral drug delivery, formulation, free drug, functional groups, group, higher solubility, hydrodynamic size, immunosuppression, in vitro cell culture studies, incorporation, inflammatory bowel disease, intestinal delivery, intestinal pH., intestine, light scattering, low solubility, mofetil, mycophenolate mofetil, nanoparticles, oral administration, oral administration of mycophenolate mofetil, oral drug delivery, pH, pH-responsive functional groups, pH-responsive groups, pH-responsive nanoparticles, pH-sensitive systems, pH., patients, polymersomes, potential applications, rat studies, reduced drug absorption, release, research, scattering, sites, size, small intestine, solubility, stomach, study, synthesis, system, target, target site, therapy, toxicity, treatment, treatment of inflammatory bowel disease, unresponsive to conventional treatment

Funders

  • Danish National Research Foundation
  • Novo Nordisk Foundation
  • The Velux Foundations

Data Provider: Digital Science

LINKS
-

Matching Records in NORA

SUBJECTS
+

METRICS
+