Cargando…

Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability

The oral delivery of insoluble and enterotoxic drugs has been largely plagued by gastrointestinal irritation, side effects, and limited bioavailability. Tripterine (Tri) ranks as the hotspot of anti-inflammatory research other than inferior water-solubility and biocompatibility. This study was inten...

Descripción completa

Detalles Bibliográficos
Autores principales: Ren, Yuehong, Qi, Chunli, Ruan, Shuxian, Cao, Guangshang, Ma, Zhiguo, Zhang, Xingwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059782/
https://www.ncbi.nlm.nih.gov/pubmed/36986681
http://dx.doi.org/10.3390/pharmaceutics15030821
_version_ 1785016956997337088
author Ren, Yuehong
Qi, Chunli
Ruan, Shuxian
Cao, Guangshang
Ma, Zhiguo
Zhang, Xingwang
author_facet Ren, Yuehong
Qi, Chunli
Ruan, Shuxian
Cao, Guangshang
Ma, Zhiguo
Zhang, Xingwang
author_sort Ren, Yuehong
collection PubMed
description The oral delivery of insoluble and enterotoxic drugs has been largely plagued by gastrointestinal irritation, side effects, and limited bioavailability. Tripterine (Tri) ranks as the hotspot of anti-inflammatory research other than inferior water-solubility and biocompatibility. This study was intended to develop selenized polymer-lipid hybrid nanoparticles loading Tri (Se@Tri-PLNs) for enteritis intervention by improving its cellular uptake and bioavailability. Se@Tri-PLNs were fabricated by a solvent diffusion-in situ reduction technique and characterized by particle size, ζ potential, morphology, and entrapment efficiency (EE). The cytotoxicity, cellular uptake, oral pharmacokinetics, and in vivo anti-inflammatory effect were evaluated. The resultant Se@Tri-PLNs were 123 nm around in particle size, with a PDI of 0.183, ζ potential of −29.70 mV, and EE of 98.95%. Se@Tri-PLNs exhibited retardant drug release and better stability in the digestive fluids compared with the unmodified counterpart (Tri-PLNs). Moreover, Se@Tri-PLNs manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy. The oral bioavailability of Tri-PLNs and Se@Tri-PLNs was up to 280% and 397% relative to Tri suspensions, respectively. Furthermore, Se@Tri-PLNs demonstrated more potent in vivo anti-enteritis activity, which resulted in a marked resolution of ulcerative colitis. Polymer-lipid hybrid nanoparticles (PLNs) enabled drug supersaturation in the gut and the sustained release of Tri to facilitate absorption, while selenium surface engineering reinforced the formulation performance and in vivo anti-inflammatory efficacy. The present work provides a proof-of-concept for the combined therapy of inflammatory bowel disease (IBD) using phytomedicine and Se in an integrated nanosystem. Selenized PLNs loading anti-inflammatory phytomedicine may be valuable for the treatment of intractable inflammatory diseases.
format Online
Article
Text
id pubmed-10059782
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-100597822023-03-30 Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability Ren, Yuehong Qi, Chunli Ruan, Shuxian Cao, Guangshang Ma, Zhiguo Zhang, Xingwang Pharmaceutics Article The oral delivery of insoluble and enterotoxic drugs has been largely plagued by gastrointestinal irritation, side effects, and limited bioavailability. Tripterine (Tri) ranks as the hotspot of anti-inflammatory research other than inferior water-solubility and biocompatibility. This study was intended to develop selenized polymer-lipid hybrid nanoparticles loading Tri (Se@Tri-PLNs) for enteritis intervention by improving its cellular uptake and bioavailability. Se@Tri-PLNs were fabricated by a solvent diffusion-in situ reduction technique and characterized by particle size, ζ potential, morphology, and entrapment efficiency (EE). The cytotoxicity, cellular uptake, oral pharmacokinetics, and in vivo anti-inflammatory effect were evaluated. The resultant Se@Tri-PLNs were 123 nm around in particle size, with a PDI of 0.183, ζ potential of −29.70 mV, and EE of 98.95%. Se@Tri-PLNs exhibited retardant drug release and better stability in the digestive fluids compared with the unmodified counterpart (Tri-PLNs). Moreover, Se@Tri-PLNs manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy. The oral bioavailability of Tri-PLNs and Se@Tri-PLNs was up to 280% and 397% relative to Tri suspensions, respectively. Furthermore, Se@Tri-PLNs demonstrated more potent in vivo anti-enteritis activity, which resulted in a marked resolution of ulcerative colitis. Polymer-lipid hybrid nanoparticles (PLNs) enabled drug supersaturation in the gut and the sustained release of Tri to facilitate absorption, while selenium surface engineering reinforced the formulation performance and in vivo anti-inflammatory efficacy. The present work provides a proof-of-concept for the combined therapy of inflammatory bowel disease (IBD) using phytomedicine and Se in an integrated nanosystem. Selenized PLNs loading anti-inflammatory phytomedicine may be valuable for the treatment of intractable inflammatory diseases. MDPI 2023-03-02 /pmc/articles/PMC10059782/ /pubmed/36986681 http://dx.doi.org/10.3390/pharmaceutics15030821 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ren, Yuehong
Qi, Chunli
Ruan, Shuxian
Cao, Guangshang
Ma, Zhiguo
Zhang, Xingwang
Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title_full Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title_fullStr Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title_full_unstemmed Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title_short Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability
title_sort selenized polymer-lipid hybrid nanoparticles for oral delivery of tripterine with ameliorative oral anti-enteritis activity and bioavailability
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10059782/
https://www.ncbi.nlm.nih.gov/pubmed/36986681
http://dx.doi.org/10.3390/pharmaceutics15030821
work_keys_str_mv AT renyuehong selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability
AT qichunli selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability
AT ruanshuxian selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability
AT caoguangshang selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability
AT mazhiguo selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability
AT zhangxingwang selenizedpolymerlipidhybridnanoparticlesfororaldeliveryoftripterinewithameliorativeoralantienteritisactivityandbioavailability