Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment

This study aimed to construct a pH-responsive nanocrystalline hydrogel drug delivery system for topical delivery of insoluble drugs based on the self-assembly behavior of carboxymethyl chitosan (CMC) and oxidized hyaluronic acid (OHA). The tanshinone nanocrystal (TNCs) extract was prepared by dielec...

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Main Authors: Xiaohan Tang, Yan Liu, Hailong Yuan, Rong Gao
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/15/12/1534
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author Xiaohan Tang
Yan Liu
Hailong Yuan
Rong Gao
author_facet Xiaohan Tang
Yan Liu
Hailong Yuan
Rong Gao
author_sort Xiaohan Tang
collection DOAJ
description This study aimed to construct a pH-responsive nanocrystalline hydrogel drug delivery system for topical delivery of insoluble drugs based on the self-assembly behavior of carboxymethyl chitosan (CMC) and oxidized hyaluronic acid (OHA). The tanshinone nanocrystal (TNCs) extract was prepared by dielectric milling method, the type and ratio of stabilizer of the drug were investigated to optimize the prescription, and the effector surface method was used to optimize the preparation process. OHA was prepared by the sodium periodate oxidation method, and the concentration of CMC and OHA was optimized using gel formation time as an indicator. OHA was dissolved in TNCs and self-assembled with CMC solution to form tanshinone extract nanocrystal hydrogels (CMC-OHA/TNCs), of which the physicochemical properties and in vitro antibacterial activity were evaluated. Results showed that the optimized prescription and process could produce tanshinone extract nanocrystals with a particle size of (223.67 ± 4.03) nm and a polydispersity index (PDI) of 0.2173 ± 0.0008. According to SEM and XRD results, TNCs were completely wrapped in the hydrogel as nanoparticles, and the crystallinity of TNCs was reduced and the diffraction peaks in CMC-OHA/TNCs almost disappeared. In vitro, transdermal test results showed that CMC-OHA/TNCs could release the drug continuously at the acne lesions. The cell-counting kit-8 (CCK-8) assay confirmed that the CMC-OHA/TNCs had no obvious cytotoxicity. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CMC-OHA/TNCs against <i>Propionibacterium acnes</i> and <i>Staphylococcus aureus</i> were significantly lower and the diameter of the inhibition circle was obviously higher than that of TNCs and tanshinone extract crude suspension. This study demonstrated that CMC-OHA/TNCs was a promising delivery system for topical delivery of insoluble drugs, which could improve the solubility of tanshinone extract and enhance its in vitro bacterial inhibitory activity.
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spelling doaj.art-ba9fefbddee54fc49de255991f04e2322023-11-24T17:16:51ZengMDPI AGPharmaceuticals1424-82472022-12-011512153410.3390/ph15121534Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne TreatmentXiaohan Tang0Yan Liu1Hailong Yuan2Rong Gao3Department of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaDepartment of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, ChinaDepartment of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, ChinaThis study aimed to construct a pH-responsive nanocrystalline hydrogel drug delivery system for topical delivery of insoluble drugs based on the self-assembly behavior of carboxymethyl chitosan (CMC) and oxidized hyaluronic acid (OHA). The tanshinone nanocrystal (TNCs) extract was prepared by dielectric milling method, the type and ratio of stabilizer of the drug were investigated to optimize the prescription, and the effector surface method was used to optimize the preparation process. OHA was prepared by the sodium periodate oxidation method, and the concentration of CMC and OHA was optimized using gel formation time as an indicator. OHA was dissolved in TNCs and self-assembled with CMC solution to form tanshinone extract nanocrystal hydrogels (CMC-OHA/TNCs), of which the physicochemical properties and in vitro antibacterial activity were evaluated. Results showed that the optimized prescription and process could produce tanshinone extract nanocrystals with a particle size of (223.67 ± 4.03) nm and a polydispersity index (PDI) of 0.2173 ± 0.0008. According to SEM and XRD results, TNCs were completely wrapped in the hydrogel as nanoparticles, and the crystallinity of TNCs was reduced and the diffraction peaks in CMC-OHA/TNCs almost disappeared. In vitro, transdermal test results showed that CMC-OHA/TNCs could release the drug continuously at the acne lesions. The cell-counting kit-8 (CCK-8) assay confirmed that the CMC-OHA/TNCs had no obvious cytotoxicity. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CMC-OHA/TNCs against <i>Propionibacterium acnes</i> and <i>Staphylococcus aureus</i> were significantly lower and the diameter of the inhibition circle was obviously higher than that of TNCs and tanshinone extract crude suspension. This study demonstrated that CMC-OHA/TNCs was a promising delivery system for topical delivery of insoluble drugs, which could improve the solubility of tanshinone extract and enhance its in vitro bacterial inhibitory activity.https://www.mdpi.com/1424-8247/15/12/1534nanocrystalsself-assembledhydrogelsacnepoorly water-soluble drug
spellingShingle Xiaohan Tang
Yan Liu
Hailong Yuan
Rong Gao
Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
Pharmaceuticals
nanocrystals
self-assembled
hydrogels
acne
poorly water-soluble drug
title Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
title_full Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
title_fullStr Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
title_full_unstemmed Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
title_short Development of a Self-Assembled Hydrogels Based on Carboxymethyl Chitosan and Oxidized Hyaluronic Acid Containing Tanshinone Extract Nanocrystals for Enhanced Dissolution and Acne Treatment
title_sort development of a self assembled hydrogels based on carboxymethyl chitosan and oxidized hyaluronic acid containing tanshinone extract nanocrystals for enhanced dissolution and acne treatment
topic nanocrystals
self-assembled
hydrogels
acne
poorly water-soluble drug
url https://www.mdpi.com/1424-8247/15/12/1534
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AT yanliu developmentofaselfassembledhydrogelsbasedoncarboxymethylchitosanandoxidizedhyaluronicacidcontainingtanshinoneextractnanocrystalsforenhanceddissolutionandacnetreatment
AT hailongyuan developmentofaselfassembledhydrogelsbasedoncarboxymethylchitosanandoxidizedhyaluronicacidcontainingtanshinoneextractnanocrystalsforenhanceddissolutionandacnetreatment
AT ronggao developmentofaselfassembledhydrogelsbasedoncarboxymethylchitosanandoxidizedhyaluronicacidcontainingtanshinoneextractnanocrystalsforenhanceddissolutionandacnetreatment