Article(id=1320107592886632601, tenantId=1146029695717560320, journalId=1263187385517883426, issueId=1320107562284986563, articleNumber=null, orderNo=null, doi=10.14062/j.issn.0454-5648.20250406, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1748188800000, receivedDateStr=2025-05-26, revisedDate=1751385600000, revisedDateStr=2025-07-02, acceptedDate=null, acceptedDateStr=null, onlineDate=1792667776556, onlineDateStr=2026-10-22, pubDate=1757606400000, pubDateStr=2025-09-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1792667776556, onlineIssueDateStr=2026-10-22, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1792667776556, creator=13701087609, updateTime=1792667776556, updator=13701087609, issue=Issue{id=1320107562284986563, tenantId=1146029695717560320, journalId=1263187385517883426, year='2026', volume='54', issue='8', pageStart='2577', pageEnd='2948', issueExtLink='null', onlineDate='null', pubDate='1787155200000', pubDateStr='2026-08-20', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1792667769261, creator='13701087609', updateTime=1792720485859, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1320328671789957452, tenantId=1146029695717560320, journalId=1263187385517883426, issueId=1320107562284986563, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1320328671789957453, tenantId=1146029695717560320, journalId=1263187385517883426, issueId=1320107562284986563, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2887, endPage=2899, ext={EN=ArticleExt(id=1320107593092153498, articleId=1320107592886632601, tenantId=1146029695717560320, journalId=1263187385517883426, language=EN, title=Enhanced Adsorption and Controlled Release Performance for Ibuprofen by Dodecyl Glucoside-Intercalated Montmorillonite, columnId=1263922769897599102, journalTitle=Journal of the Chinese Ceramic Society, columnName=Research Articles, runingTitle=null, highlight=null, articleAbstract=
Introduction

Montmorillonite (Mt) has been extensively applied in drug delivery systems owing to its high cation exchange capacity, large specific surface area, and biocompatibility. However, its strong hydrophilicity and interlayer water molecules significantly restrict the efficient loading of hydrophobic drugs (e.g., ibuprofen (IBU)). Organic modification using surfactants can enhance Mt's hydrophobicity, where cationic types dominate as mainstream modifiers due to their efficient ion-exchange characteristics, capable of expanding interlayer spacing and optimizing drug compatibility. Nevertheless, anionic surfactants rely on anion-dipole interaction adsorption, while nonionic surfactants, despite advantages in low toxicity and biodegradability, exhibit inferior binding efficiency with limited research on related drug carriers. Recently, green nonionic alkyl polyglucosides have attracted considerable attention for their environmental friendliness, superior interfacial activity, and biosafety. This study employed dodecyl glucoside (DPG) to fabricate DPG-Mt composite carriers through wet ball-milling intercalation modification. It systematically investigated the intercalation mechanisms between nonionic surfactants and Mt, along with drug-loading performance and release behaviors, aiming to overcome limitations of conventional ionic modifiers and elucidate the efficiency-enhancing principles of nonionic modification in drug delivery systems. This research not only provides novel strategies for developing safe and stable Mt-based drug delivery systems but also advances technological innovation in green pharmaceutics, demonstrating significant theoretical and practical implications.

Method

This study employed green and safe nonionic DPG to prepare a safe and biocompatible DPG-Mt based pharmaceutical formulation through intercalation modification of natural Mt using a wet ball-milling technique. The synthesized DPG-Mt was systematically characterized for its morphology, crystal structure, functional groups, thermal stability, and colloidal properties using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy (RS), thermogravimetric analysis (TGA), BET surface area analysis, and Malvern laser particle size analysis. By investigating the effects of various DPG content on the structure and properties of DPG-Mt, the mechanistic role of DPG in modifying Mt was elucidated, and the adsorption capacity of DPG-Mt for the anti-inflammatory drug, IBU was evaluated. Finally, simulated drug release experiments were conducted to examine the IBU release behavior from drug-loaded DPG-Mt, while cytotoxicity assays were performed to assess its biocompatibility, thereby validating its potential for biomedical applications.

Results and discussion

The characterization results of DPG-Mt revealed that the wet ball-milling process did not disrupt or exfoliate the layered structure of Mt. Instead, under the compressive, impact, and frictional forces of mechanical ball-milling, the particle size of Mt was significantly reduced. DPG overcame the weak electrostatic forces, van der Waals interactions, and hydrogen bonding between stacked Mt layers, adsorbing and intercalating into its interlayer spaces, thereby expanding the interlayer spacing of DPG-Mt. Specifically, the interlayer spacings of 1.0DPG-Mt, 2.0DPG-Mt, and 3.0DPG-Mt increased to 1.47 nm (2θ = 6.0°), 1.55 nm (2θ = 5.7°), and 1.52 nm (2θ = 5.8°), respectively. Raman spectroscopy and BET surface area analysis demonstrated that nonionic DPG did not form chemical bonds with DPG-Mt but was physically intercalated into the interlayers via hydrogen bonding and electrostatic interactions. The BET surface area of Na-Mt increased from 62.6 m2/g to 72.0 m2/g under mechanical ball-milling, likely due to the fragmentation of large Mt particles during the modification process. However, the adsorption and intercalation of DPG into DPG-Mt partially obstructed pore channels, leading to a reduction in pore volume and average pore size from 0.337 mL/g and 4.61 nm to 0.245 mL/g and 2.15 nm, respectively.

Concurrently, after organic modification, the particle size of DPG-Mt decreased from 984.0 nm (PDI = 0.34) to 605.0 nm (PDI=0.31), while its zeta potential increased from -39.7 mV to -22.5 mV. These results indicated that the adsorption and intercalation of DPG not only inhibited particle aggregation but also reduced surface charge density. Furthermore, the interfacial tension (IFT) of the DPG-Mt aqueous suspension significantly decreased from 72.75 × 10-3 N·m-1 to 41.12 × 10-3 N·m-1 after modification. This phenomenon can be attributed to the hydrophobic dodecyl chains of intercalated DPG, which weakened the hydrophilicity of DPG-Mt and enhanced its interfacial activity. Adsorption experiments to IBU demonstrated that organic modification increased the saturated adsorption capacity (Qm) of Mt for IBU from 35.336 mg/g to 46.083 mg/g, with IBU adsorption on DPG-Mt favoring a multilayer mechanism. In vitro drug release and cytotoxicity analyses revealed that both Mt and DPG-Mt exhibited sustained release of IBU over 480 min. Notably, the biocompatible DPG-modified Mt (DPG-Mt) displayed superior biocompatibility, underscoring the synergistic benefits of organic modification in optimizing drug delivery performance while maintaining biosafety.

Conclusions

The wet ball-milling process exerted compressive, impact, and frictional forces on Mt, leading to reduced particle size, increased specific surface area, and enhanced colloidal interfacial activity of DPG-Mt. The organic modification of Mt by DPG occurred via physical intercalation, where DPG was physically embedded into the interlayer spaces of Mt under mechanical forces. This not only expanded the interlayer spacing and improved the thermal stability of the intercalated DPG but also effectively altered the strong polarity of Mt, thereby enhancing its affinity for the hydrophobic IBU. Consequently, the saturated adsorption capacity of Mt for IBU increased from 35.336 mg/g to 46.083 mg/g. Owing to the superior adsorption performance of DPG-Mt to IBU, DPG-Mt exhibited sustained drug release over 480 min, demonstrating favorable sustained-release performance, with the released IBU amounting to 76% of the total dosage. Cytotoxicity tests further confirmed that the organic modification of Mt with DPG conferred excellent cytocompatibility to DPG-Mt. Given its high drug adsorption capacity, excellent sustained-release properties, and outstanding cytocompatibility, DPG-Mt demonstrates significant potential as a hydrophobic anti-inflammatory drug formulation for biomedical applications.

, authors=Yanan BU1, 2, 3, Xiuqiong CHEN1, 2, 3, Jiji FAN2, 3, Shiyu HUANG2, 3, Huiqiong YAN1, 2, 3, Qiang LIN1, 2, 3, authorsList=Yanan BU, Xiuqiong CHEN, Jiji FAN, Shiyu HUANG, Huiqiong YAN, Qiang LIN, authorCompany=null, correspAuthors=Huiqiong YAN, authorNote=

BU Yanan (1997-), female, Doctoral candidate. E-mail:

, correspAuthorsNote=
{YAN} Huiqiong (1986-), male, Ph.D., Associate Professor. E-mail:
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为了阐明在机械作用下非离子表面活性剂对天然蒙脱石(Mt)有机改性的机理及其载药性能与释放行为,以安全而稳定的十二烷基糖苷(DPG)作为改性剂,通过湿法球磨法制备了DPG改性有机蒙脱石(DPG-Mt)。测试结果表明,湿法球磨过程对Mt起到了挤压、碰撞和摩擦作用,使DPG-Mt粒径变小、比表面积增大、胶体界面活性增强。DPG对Mt的有机改性方式是物理插层,即在机械作用力的辅助下,将DPG以物理嵌入的方式插入了Mt的夹层间,不仅增大了其层间距,提高了层间DPG的热稳定性,而且有效地改变了Mt的强极性,增强了其与疏水性布洛芬(IBU)药物的亲和力,使其对IBU的饱和吸附量从35.336 mg/g增长至46.083 mg/g。而且由于DPG-Mt对IBU较好的吸附性能,DPG-Mt可以持续释放药物达480 min,展现了良好的缓释性能,且释放的IBU药剂量相当于总剂量的76%。最后,通过细胞毒性实验测试结果表明,DPG对Mt的有机改性可以赋予DPG-Mt良好的细胞相容性。基于DPG-Mt的较高药物吸附性、良好缓释性能及优异细胞相容性,该材料在生物制药领域展现出潜在的应用价值。

, authors=步亚楠1, 2, 3, 陈秀琼1, 2, 3, 范吉吉2, 3, 黄诗雨2, 3, 颜慧琼1, 2, 3, 林强1, 2, 3, authorsList=步亚楠, 陈秀琼, 范吉吉, 黄诗雨, 颜慧琼, 林强, authorCompany=null, correspAuthors=颜慧琼, authorNote=

步亚楠(1997—),女,博士研究生。

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颜慧琼(1986—),男,博士,副教授。
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十二烷基糖苷插层改性蒙脱石及其对布洛芬的吸附和控释性能
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步亚楠 1, 2, 3 , 陈秀琼 1, 2, 3 , 范吉吉 2, 3 , 黄诗雨 2, 3 , 颜慧琼 1, 2, 3 , 林强 1, 2, 3
硅酸盐学报 | 研究论文 2026,54(8): 2887-2899
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硅酸盐学报 |研究论文 2026 , 54 (8) : 2887 -2899
十二烷基糖苷插层改性蒙脱石及其对布洛芬的吸附和控释性能
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步亚楠1, 2, 3 , 陈秀琼1, 2, 3, 范吉吉2, 3, 黄诗雨2, 3, 颜慧琼1, 2, 3 , 林强1, 2, 3
作者信息
  • 1.海南师范大学热带药用植物资源教育部重点实验室和海南省热带药用植物化学重点实验室,海口 571158
  • 2.海南省水环境污染治理与资源化重点实验室,海口 571158
  • 3.海口市天然高分子功能材料重点实验室,海口 571158
通讯作者:
颜慧琼(1986—),男,博士,副教授。
作者简介:

步亚楠(1997—),女,博士研究生。

Enhanced Adsorption and Controlled Release Performance for Ibuprofen by Dodecyl Glucoside-Intercalated Montmorillonite
Yanan BU1, 2, 3 , Xiuqiong CHEN1, 2, 3, Jiji FAN2, 3, Shiyu HUANG2, 3, Huiqiong YAN1, 2, 3 , Qiang LIN1, 2, 3
Affiliations
  • 1.Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, Hainan Normal University, Haikou 571158, China
  • 2.Key Laboratory of Water Pollution Treatment and Resource Reuse of Hainan Province, Haikou 571158, China
  • 3.Key Laboratory of Natural Polymer Functional Material of Haikou City, Haikou 571158, China
  • Corresponding Author:
    {YAN} Huiqiong (1986-), male, Ph.D., Associate Professor. E-mail:

    BU Yanan (1997-), female, Doctoral candidate. E-mail:

出版时间: 2025-09-12 doi: 10.14062/j.issn.0454-5648.20250406
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为了阐明在机械作用下非离子表面活性剂对天然蒙脱石(Mt)有机改性的机理及其载药性能与释放行为,以安全而稳定的十二烷基糖苷(DPG)作为改性剂,通过湿法球磨法制备了DPG改性有机蒙脱石(DPG-Mt)。测试结果表明,湿法球磨过程对Mt起到了挤压、碰撞和摩擦作用,使DPG-Mt粒径变小、比表面积增大、胶体界面活性增强。DPG对Mt的有机改性方式是物理插层,即在机械作用力的辅助下,将DPG以物理嵌入的方式插入了Mt的夹层间,不仅增大了其层间距,提高了层间DPG的热稳定性,而且有效地改变了Mt的强极性,增强了其与疏水性布洛芬(IBU)药物的亲和力,使其对IBU的饱和吸附量从35.336 mg/g增长至46.083 mg/g。而且由于DPG-Mt对IBU较好的吸附性能,DPG-Mt可以持续释放药物达480 min,展现了良好的缓释性能,且释放的IBU药剂量相当于总剂量的76%。最后,通过细胞毒性实验测试结果表明,DPG对Mt的有机改性可以赋予DPG-Mt良好的细胞相容性。基于DPG-Mt的较高药物吸附性、良好缓释性能及优异细胞相容性,该材料在生物制药领域展现出潜在的应用价值。

蒙脱石  /  有机改性  /  十二烷基糖苷  /  球磨法  /  药物吸附  /  布洛芬
Introduction

Montmorillonite (Mt) has been extensively applied in drug delivery systems owing to its high cation exchange capacity, large specific surface area, and biocompatibility. However, its strong hydrophilicity and interlayer water molecules significantly restrict the efficient loading of hydrophobic drugs (e.g., ibuprofen (IBU)). Organic modification using surfactants can enhance Mt's hydrophobicity, where cationic types dominate as mainstream modifiers due to their efficient ion-exchange characteristics, capable of expanding interlayer spacing and optimizing drug compatibility. Nevertheless, anionic surfactants rely on anion-dipole interaction adsorption, while nonionic surfactants, despite advantages in low toxicity and biodegradability, exhibit inferior binding efficiency with limited research on related drug carriers. Recently, green nonionic alkyl polyglucosides have attracted considerable attention for their environmental friendliness, superior interfacial activity, and biosafety. This study employed dodecyl glucoside (DPG) to fabricate DPG-Mt composite carriers through wet ball-milling intercalation modification. It systematically investigated the intercalation mechanisms between nonionic surfactants and Mt, along with drug-loading performance and release behaviors, aiming to overcome limitations of conventional ionic modifiers and elucidate the efficiency-enhancing principles of nonionic modification in drug delivery systems. This research not only provides novel strategies for developing safe and stable Mt-based drug delivery systems but also advances technological innovation in green pharmaceutics, demonstrating significant theoretical and practical implications.

Method

This study employed green and safe nonionic DPG to prepare a safe and biocompatible DPG-Mt based pharmaceutical formulation through intercalation modification of natural Mt using a wet ball-milling technique. The synthesized DPG-Mt was systematically characterized for its morphology, crystal structure, functional groups, thermal stability, and colloidal properties using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy (RS), thermogravimetric analysis (TGA), BET surface area analysis, and Malvern laser particle size analysis. By investigating the effects of various DPG content on the structure and properties of DPG-Mt, the mechanistic role of DPG in modifying Mt was elucidated, and the adsorption capacity of DPG-Mt for the anti-inflammatory drug, IBU was evaluated. Finally, simulated drug release experiments were conducted to examine the IBU release behavior from drug-loaded DPG-Mt, while cytotoxicity assays were performed to assess its biocompatibility, thereby validating its potential for biomedical applications.

Results and discussion

The characterization results of DPG-Mt revealed that the wet ball-milling process did not disrupt or exfoliate the layered structure of Mt. Instead, under the compressive, impact, and frictional forces of mechanical ball-milling, the particle size of Mt was significantly reduced. DPG overcame the weak electrostatic forces, van der Waals interactions, and hydrogen bonding between stacked Mt layers, adsorbing and intercalating into its interlayer spaces, thereby expanding the interlayer spacing of DPG-Mt. Specifically, the interlayer spacings of 1.0DPG-Mt, 2.0DPG-Mt, and 3.0DPG-Mt increased to 1.47 nm (2θ = 6.0°), 1.55 nm (2θ = 5.7°), and 1.52 nm (2θ = 5.8°), respectively. Raman spectroscopy and BET surface area analysis demonstrated that nonionic DPG did not form chemical bonds with DPG-Mt but was physically intercalated into the interlayers via hydrogen bonding and electrostatic interactions. The BET surface area of Na-Mt increased from 62.6 m2/g to 72.0 m2/g under mechanical ball-milling, likely due to the fragmentation of large Mt particles during the modification process. However, the adsorption and intercalation of DPG into DPG-Mt partially obstructed pore channels, leading to a reduction in pore volume and average pore size from 0.337 mL/g and 4.61 nm to 0.245 mL/g and 2.15 nm, respectively.

Concurrently, after organic modification, the particle size of DPG-Mt decreased from 984.0 nm (PDI = 0.34) to 605.0 nm (PDI=0.31), while its zeta potential increased from -39.7 mV to -22.5 mV. These results indicated that the adsorption and intercalation of DPG not only inhibited particle aggregation but also reduced surface charge density. Furthermore, the interfacial tension (IFT) of the DPG-Mt aqueous suspension significantly decreased from 72.75 × 10-3 N·m-1 to 41.12 × 10-3 N·m-1 after modification. This phenomenon can be attributed to the hydrophobic dodecyl chains of intercalated DPG, which weakened the hydrophilicity of DPG-Mt and enhanced its interfacial activity. Adsorption experiments to IBU demonstrated that organic modification increased the saturated adsorption capacity (Qm) of Mt for IBU from 35.336 mg/g to 46.083 mg/g, with IBU adsorption on DPG-Mt favoring a multilayer mechanism. In vitro drug release and cytotoxicity analyses revealed that both Mt and DPG-Mt exhibited sustained release of IBU over 480 min. Notably, the biocompatible DPG-modified Mt (DPG-Mt) displayed superior biocompatibility, underscoring the synergistic benefits of organic modification in optimizing drug delivery performance while maintaining biosafety.

Conclusions

The wet ball-milling process exerted compressive, impact, and frictional forces on Mt, leading to reduced particle size, increased specific surface area, and enhanced colloidal interfacial activity of DPG-Mt. The organic modification of Mt by DPG occurred via physical intercalation, where DPG was physically embedded into the interlayer spaces of Mt under mechanical forces. This not only expanded the interlayer spacing and improved the thermal stability of the intercalated DPG but also effectively altered the strong polarity of Mt, thereby enhancing its affinity for the hydrophobic IBU. Consequently, the saturated adsorption capacity of Mt for IBU increased from 35.336 mg/g to 46.083 mg/g. Owing to the superior adsorption performance of DPG-Mt to IBU, DPG-Mt exhibited sustained drug release over 480 min, demonstrating favorable sustained-release performance, with the released IBU amounting to 76% of the total dosage. Cytotoxicity tests further confirmed that the organic modification of Mt with DPG conferred excellent cytocompatibility to DPG-Mt. Given its high drug adsorption capacity, excellent sustained-release properties, and outstanding cytocompatibility, DPG-Mt demonstrates significant potential as a hydrophobic anti-inflammatory drug formulation for biomedical applications.

montmorillonite  /  organic modification  /  dodecyl glycoside  /  mechanical ball milling technology  /  drug adsorption  /  ibuprofen
步亚楠, 陈秀琼, 范吉吉, 黄诗雨, 颜慧琼, 林强. 十二烷基糖苷插层改性蒙脱石及其对布洛芬的吸附和控释性能. 硅酸盐学报, 2026 , 54 (8) : 2887 -2899 . DOI: 10.14062/j.issn.0454-5648.20250406
Yanan BU, Xiuqiong CHEN, Jiji FAN, Shiyu HUANG, Huiqiong YAN, Qiang LIN. Enhanced Adsorption and Controlled Release Performance for Ibuprofen by Dodecyl Glucoside-Intercalated Montmorillonite[J]. Journal of the Chinese Ceramic Society, 2026 , 54 (8) : 2887 -2899 . DOI: 10.14062/j.issn.0454-5648.20250406
  • 国家自然科学基金项目(51963009)
  • 海南省重点研发项目(ZDYF2023SHFZ124)
  • 海南省高层次人才基金项目(225RC749)
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doi: 10.14062/j.issn.0454-5648.20250406
  • 接收时间:2025-05-26
  • 首发时间:2026-10-22
  • 出版时间:2025-09-12
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  • 收稿日期:2025-05-26
  • 修回日期:2025-07-02
基金
国家自然科学基金项目(51963009)
海南省重点研发项目(ZDYF2023SHFZ124)
海南省高层次人才基金项目(225RC749)
作者信息
    1.海南师范大学热带药用植物资源教育部重点实验室和海南省热带药用植物化学重点实验室,海口 571158
    2.海南省水环境污染治理与资源化重点实验室,海口 571158
    3.海口市天然高分子功能材料重点实验室,海口 571158

通讯作者:

颜慧琼(1986—),男,博士,副教授。
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
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