TY - JOUR

T1 - Tailored Polymersomes for Enhanced Oral Drug Delivery

T2 - pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants

AU - Tollemeto, Matteo

AU - Ursulska, Sintija

AU - Welzen, Pascal L.W.

AU - Thamdrup, Lasse H.E.

AU - Malakpour Permlid, Atena

AU - Li, Yudong

AU - Soufi, Gohar

AU - Patiño Padial, Tania

AU - Christensen, Jørn B.

AU - Hagner Nielsen, Line

AU - van Hest, Jan

AU - Boisen, Anja

N1 - Funding Information: The authors would like to acknowledge the Danish National Research Foundation (DNRF122) and Villum Fonden (Grant No. 9301) for intelligent drug delivery and sensing using microcontainers and nanomechanics (IDUN) and the Novo Nordisk Foundation (NNF17OC0026910). Publisher Copyright: © 2024 The Author(s). Small published by Wiley-VCH GmbH.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - IBD

KW - mucosal barriers

KW - mycophenolate mofetil

KW - oral administration

KW - polymersomes

U2 - 10.1002/smll.202403640

DO - 10.1002/smll.202403640

M3 - Journal article

C2 - 38963162

AN - SCOPUS:85197854595

JO - Small

JF - Small

SN - 1613-6810

M1 - 2403640

ER -