Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells

Context Oridonin (ORI) has obvious anticancer effects, but its solubility is poor. Nanocrystal (NC) is a novel nano-drug delivery system for increasing bioavailability for ORI. However, the endocytosis and transcytosis behaviours of oridonin nanocrystals (ORI-NCs) through epithelial membrane are sti...

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Main Authors: Huagang Sheng, Yuanyuan Zhang, Jijuan Nai, Shaohua Wang, Mengmeng Dai, Guitao Lin, Liqiao Zhu, Qiang Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Pharmaceutical Biology
Subjects:
Online Access:http://dx.doi.org/10.1080/13880209.2020.1767160
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author Huagang Sheng
Yuanyuan Zhang
Jijuan Nai
Shaohua Wang
Mengmeng Dai
Guitao Lin
Liqiao Zhu
Qiang Zhang
author_facet Huagang Sheng
Yuanyuan Zhang
Jijuan Nai
Shaohua Wang
Mengmeng Dai
Guitao Lin
Liqiao Zhu
Qiang Zhang
author_sort Huagang Sheng
collection DOAJ
description Context Oridonin (ORI) has obvious anticancer effects, but its solubility is poor. Nanocrystal (NC) is a novel nano-drug delivery system for increasing bioavailability for ORI. However, the endocytosis and transcytosis behaviours of oridonin nanocrystals (ORI-NCs) through epithelial membrane are still unclear. Objectives ORI-NCs were prepared and characterized. The in vitro cytotoxicity and endocytosis and transcytosis process on Madin-Darby canine kidney (MDCK) monolayer were investigated. Materials and methods Anti-solvent precipitation method was adopted in preparation of ORI-NCs. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were adopted to explore crystallography of ORI-NCs. Sulforhodamine B (SRB) method was used to test the inhibition effect on proliferation of MDCK cells. Quantitative analysis by HPLC was performed to study the endocytosis and transcytosis of ORI-NCs and ORI bulk drug, and the process was observed by confocal laser spectrum microscopy (CLSM) and flow cytometry. Results The particle size of ORI-NCs was about 274 nm. The crystallography form of ORI was not changed after prepared into NCs. The dissolution rate of ORI-NCs was higher than pure ORI in 120 min. At higher concentrations (34, 84 and 135 μg/mL), ORI-NCs significantly reduced the cell viability compared with free ORI (p < 0.05, p < 0.01). ORI-NCs demonstrated higher endocytosis in MDCK cells than free ORI (p < 0.01). In the transport process, ORI-NC was taken up into cells in an intact form, and excreted out from basolateral membrane of polarized epithelial cells in an intact form. The internalization and transmembrane amount increased as a function of time. Conclusions ORI-NCs transported through the MDCK monolayers in an intact form.
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spelling doaj.art-27dc3139e1f3444e8f13394989dd76af2022-12-21T20:40:44ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162020-01-0158151852710.1080/13880209.2020.17671601767160Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cellsHuagang Sheng0Yuanyuan Zhang1Jijuan Nai2Shaohua Wang3Mengmeng Dai4Guitao Lin5Liqiao Zhu6Qiang Zhang7College of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineCollege of Pharmacy, Shandong University of Traditional Chinese MedicineState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science CenterContext Oridonin (ORI) has obvious anticancer effects, but its solubility is poor. Nanocrystal (NC) is a novel nano-drug delivery system for increasing bioavailability for ORI. However, the endocytosis and transcytosis behaviours of oridonin nanocrystals (ORI-NCs) through epithelial membrane are still unclear. Objectives ORI-NCs were prepared and characterized. The in vitro cytotoxicity and endocytosis and transcytosis process on Madin-Darby canine kidney (MDCK) monolayer were investigated. Materials and methods Anti-solvent precipitation method was adopted in preparation of ORI-NCs. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were adopted to explore crystallography of ORI-NCs. Sulforhodamine B (SRB) method was used to test the inhibition effect on proliferation of MDCK cells. Quantitative analysis by HPLC was performed to study the endocytosis and transcytosis of ORI-NCs and ORI bulk drug, and the process was observed by confocal laser spectrum microscopy (CLSM) and flow cytometry. Results The particle size of ORI-NCs was about 274 nm. The crystallography form of ORI was not changed after prepared into NCs. The dissolution rate of ORI-NCs was higher than pure ORI in 120 min. At higher concentrations (34, 84 and 135 μg/mL), ORI-NCs significantly reduced the cell viability compared with free ORI (p < 0.05, p < 0.01). ORI-NCs demonstrated higher endocytosis in MDCK cells than free ORI (p < 0.01). In the transport process, ORI-NC was taken up into cells in an intact form, and excreted out from basolateral membrane of polarized epithelial cells in an intact form. The internalization and transmembrane amount increased as a function of time. Conclusions ORI-NCs transported through the MDCK monolayers in an intact form.http://dx.doi.org/10.1080/13880209.2020.1767160poor water solubilitybottom-up methodmdck monolayertranscellular transport
spellingShingle Huagang Sheng
Yuanyuan Zhang
Jijuan Nai
Shaohua Wang
Mengmeng Dai
Guitao Lin
Liqiao Zhu
Qiang Zhang
Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
Pharmaceutical Biology
poor water solubility
bottom-up method
mdck monolayer
transcellular transport
title Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
title_full Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
title_fullStr Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
title_full_unstemmed Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
title_short Preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on MDCK polarized epithelial cells
title_sort preparation of oridonin nanocrystals and study of their endocytosis and transcytosis behaviours on mdck polarized epithelial cells
topic poor water solubility
bottom-up method
mdck monolayer
transcellular transport
url http://dx.doi.org/10.1080/13880209.2020.1767160
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