Tailored Polymersomes for Enhanced Oral Drug Delivery: pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants
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Tailored Polymersomes for Enhanced Oral Drug Delivery : pH-Sensitive Systems for Intestinal Delivery of Immunosuppressants. / Tollemeto, Matteo; Ursulska, Sintija; Welzen, Pascal L.W.; Thamdrup, Lasse H.E.; Malakpour Permlid, Atena; Li, Yudong; Soufi, Gohar; Patiño Padial, Tania; Christensen, Jørn B.; Hagner Nielsen, Line; van Hest, Jan; Boisen, Anja.
I: Small, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 398972757