Cargando…

Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin

Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application....

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Yinzhuo, Xu, Wei, Jin, Zheng, Zhao, Kai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333679/
https://www.ncbi.nlm.nih.gov/pubmed/37441137
http://dx.doi.org/10.1016/j.mtbio.2023.100617
_version_ 1785070715931721728
author Xie, Yinzhuo
Xu, Wei
Jin, Zheng
Zhao, Kai
author_facet Xie, Yinzhuo
Xu, Wei
Jin, Zheng
Zhao, Kai
author_sort Xie, Yinzhuo
collection PubMed
description Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR (CUR@Chs-PNC NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated CUR@Chs-PNC NPs had an ideal average particle size (238.9 ​nm), a uniform size distribution, and a positive surface charge (+41.93 ​mV). Strikingly, the CUR@Chs-PNC NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the CUR@Chs-PNC NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the CUR@Chs-PNC NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that CUR@Chs-PNC NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis.
format Online
Article
Text
id pubmed-10333679
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-103336792023-07-12 Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin Xie, Yinzhuo Xu, Wei Jin, Zheng Zhao, Kai Mater Today Bio Full Length Article Curcumin (CUR) has a regulatory effect on the gut microbiota (GM), and its significant anti-inflammatory properties make it a research hotspot for inflammatory bowel disease (IBD) treatment. However, the low bioavailability and poor pharmacokinetic properties of CUR limit its practical application. Herein, CD44 and GM dual-targeted nanoparticles (NPs) loaded with CUR (CUR@Chs-PNC NPs) were derived from a quaternized chitosan and surface functionalization with chondroitin sulfate (Chs). The generated CUR@Chs-PNC NPs had an ideal average particle size (238.9 ​nm), a uniform size distribution, and a positive surface charge (+41.93 ​mV). Strikingly, the CUR@Chs-PNC NPs had a good sustained-release effect in a simulated gastrointestinal environment and exhibited the full drug release when in a simulated colon environment. Moreover, Chs functionalization endowed the NPs with a notable CD44-targeted drug delivery ability and thereby enhanced the CUR content in the plasma of SD rats. The biodistribution of the CUR@Chs-PNC NPs in vivo indicated that the NPs could prolong the intestinal residence time, thereby promoting the interaction between CUR and GM. Most importantly, in a DSS-induced colitis mouse model, the CUR@Chs-PNC NPs decreased the disease activity index, improved the oxidative stress and inflammation condition, promoted the production of short-chain fatty acids (SCFAs), regulated immune cells, and maintained intestinal microbiome homeostasis. This study demonstrates that CUR@Chs-PNC NPs, which exhibit excellent biocompatibility and biodegradability, on-demand drug release property, and CD44 and GM dual-targeted capacities, have the potential for further application in the treatment of colitis. Elsevier 2023-03-24 /pmc/articles/PMC10333679/ /pubmed/37441137 http://dx.doi.org/10.1016/j.mtbio.2023.100617 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Xie, Yinzhuo
Xu, Wei
Jin, Zheng
Zhao, Kai
Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title_full Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title_fullStr Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title_full_unstemmed Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title_short Chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for CD44 and gut microbiota dual-targeted delivery of curcumin
title_sort chondroitin sulfate functionalized palmitic acid and cysteine cografted-quaternized chitosan for cd44 and gut microbiota dual-targeted delivery of curcumin
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333679/
https://www.ncbi.nlm.nih.gov/pubmed/37441137
http://dx.doi.org/10.1016/j.mtbio.2023.100617
work_keys_str_mv AT xieyinzhuo chondroitinsulfatefunctionalizedpalmiticacidandcysteinecograftedquaternizedchitosanforcd44andgutmicrobiotadualtargeteddeliveryofcurcumin
AT xuwei chondroitinsulfatefunctionalizedpalmiticacidandcysteinecograftedquaternizedchitosanforcd44andgutmicrobiotadualtargeteddeliveryofcurcumin
AT jinzheng chondroitinsulfatefunctionalizedpalmiticacidandcysteinecograftedquaternizedchitosanforcd44andgutmicrobiotadualtargeteddeliveryofcurcumin
AT zhaokai chondroitinsulfatefunctionalizedpalmiticacidandcysteinecograftedquaternizedchitosanforcd44andgutmicrobiotadualtargeteddeliveryofcurcumin