Permana Zuliar, Xeliem Jovinka N, Zefrina Normalita F, Hanum Latifa F, Nirmalayanti Ni Lpkv, Permana Benny, Mudhakir Diky
Department of Pharmaceutics, School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
Department of Pharmacochemistry, School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
Narra J. 2025 Apr;5(1):e1815. doi: 10.52225/narra.v5i1.1815. Epub 2025 Jan 20.
Mesoporous silica nanoparticles (MSNs) are effective platforms for drug delivery due to their high surface area, adjustable pore sizes, and biocompatibility. The aim of this study was to explore the application of histidine-modified poly-L-lysine (PLL-His) as a pH- responsive gatekeeper to control the release of an anti-inflammatory agent, celecoxib, from MSNs. MSNs were synthesized through a sol-gel process using cetyltrimethylammonium bromide (CTAB) as a template and were functionalized with amine groups using (3-aminopropyl)triethoxysilane (APTES). Drug loading was achieved via adsorption in ethanol. Subsequently, poly-L-lysine (PLL) and PLL-His were conjugated to the MSNs using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) to form MSN-NH-Drug-PLL and MSN-NH-Drug- PLL-His constructs. Characterization of these particles was conducted using Fourier- transform infrared (FT-IR) spectroscopy, Brunauer-Emmett-Teller (BET) analysis, and particle size analysis. Results showed that the particle size of MSN-NH-drug-PLL and MSN-NH-drug-PLL-His was 237.10 ± 6.56 nm and 234.03 ± 14.65 nm, respectively, indicating suitability for cellular uptake. BET analysis confirmed the increased surface area and pore volume after the removal of CTAB, demonstrating successful mesopore formation. Drug release tests were performed in simulated gastric (pH 1.2) and physiological (pH 7.4) conditions, showing that PLL-His-modified MSNs exhibited minimal release in acidic conditions and sustained release at physiological pH. The PLL- His effectively functioned as a pH-responsive gatekeeper, enhancing drug targeting and reducing premature release. This study highlights the potential of PLL-His-modified MSNs as a promising model for pH-sensitive, targeted drug delivery, with potential applications across various therapeutic areas requiring precise release profiles. This approach could significantly improve therapeutic outcomes and patient compliance, particularly in disease contexts where pH variability is a critical factor. Overall, the integration of PLL-His as a pH-responsive gatekeeper represents a significant advancement in the design of smart drug delivery systems.
介孔二氧化硅纳米颗粒（MSNs）因其高比表面积、可调节的孔径和生物相容性，是有效的药物递送平台。本研究的目的是探索组氨酸修饰的聚-L-赖氨酸（PLL-His）作为pH响应性门控剂的应用，以控制抗炎药塞来昔布从MSNs中的释放。MSNs通过溶胶-凝胶法合成，使用十六烷基三甲基溴化铵（CTAB）作为模板，并使用（3-氨丙基）三乙氧基硅烷（APTES）用胺基进行功能化。通过在乙醇中吸附实现药物负载。随后，使用1-乙基-3-（3-二甲基氨基丙基）碳二亚胺（EDAC）和N-羟基琥珀酰亚胺（NHS）将聚-L-赖氨酸（PLL）和PLL-His与MSNs共轭，形成MSN-NH-Drug-PLL和MSN-NH-Drug-PLL-His构建体。使用傅里叶变换红外（FT-IR）光谱、布鲁诺尔-埃米特-泰勒（BET）分析和粒度分析对这些颗粒进行表征。结果表明，MSN-NH-drug-PLL和MSN-NH-drug-PLL-His的粒径分别为237.10±6.56 nm和234.03±14.65 nm，表明适合细胞摄取。BET分析证实了去除CTAB后表面积和孔体积的增加，证明成功形成了介孔。在模拟胃液（pH 1.2）和生理条件（pH 7.4）下进行药物释放测试，结果表明PLL-His修饰的MSNs在酸性条件下释放极少，在生理pH下持续释放。PLL-His有效地作为pH响应性门控剂发挥作用，增强了药物靶向性并减少了过早释放。本研究突出了PLL-His修饰的MSNs作为pH敏感、靶向药物递送的有前景模型的潜力，在需要精确释放曲线的各种治疗领域具有潜在应用。这种方法可以显著改善治疗效果和患者依从性，特别是在pH变异性是关键因素的疾病背景下。总体而言，将PLL-His作为pH响应性门控剂的整合代表了智能药物递送系统设计的重大进展。
