Construction and drug release performance of thermosensitive copolymer-modified hollow mesoporous silica and the composite nanofibers
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摘要: 传统的载药纳米纤维存在药物负载不稳定、释放过快等问题。基于此，本文利用温敏聚合物包覆中空介孔二氧化硅纳米颗粒(HMSN)，将其作为药物载体与聚己内酯(PCL)纳米纤维复合，探究了复合纳米纤维膜的释药及抗菌性能。采用自由基聚合方法在HMSN表面接枝异丙基丙烯酰胺与丙烯酰胺的共聚物(P(NIPAM-co-AM))，将疏水性药物环丙沙星(CIP)负载到共聚物改性纳米粒子(PHMSN)中，利用SEM、TEM、TG、比表面积分析(BET)、FTIR及紫外-可见吸收光谱(UV-Vis)等手段表征了HMSN和PHMSN的微观结构和温度响应性能等。将PCL与载药PHMSN共混后利用静电纺丝技术制备了复合纤维膜(CIP@PHMSN-PCL)。CIP@PHMSN-PCL具有温度刺激响应的药物控释功能，在45 ℃和25 ℃下，72 h时CIP的累积释放率分别达到90.78%和72.67%。Korsmeyer-Peppas模型较好地描述了药物释放动力学，表明扩散是复合纤维膜释药的主要机制。45 ℃条件下，载药纤维膜对大肠杆菌(E. coil)和金黄色葡萄球菌(S. aureus)的抑菌率均达到100%；而在25 ℃下，膜对两种菌的抑菌率仅为92.34%和95.83%，证明了不同温度下CIP@PHMSN-PCL膜释药性能的差异。总之，载药PHMSN复合纳米纤维膜具有环境温度调控的释药功能及优异的抗菌活性，在生物医学领域具有潜在的应用价值。Abstract: Traditional drug-loaded nanofibers face challenges such as unstable drug loading and excessively rapid release. In light of these issues, this study employs a thermosensitive copolymer (P(NIPAM-co-AM)) to coat hollow mesoporous silica nanoparticles (HMSN), incorporating them as drug carriers in conjunction with poly(ε-caprolactone) (PCL) nanofibers. The drug release and antibacterial performance of the composite nanofiber membrane were investigated. Firstly, the HMSN surface was functionalized through free radical polymerization by grafting a copolymer of isopropylacrylamide (NIPAM) and acrylamide (AM) (P(NIPAM-co-AM)). Hydrophobic drug ciprofloxacin (CIP) was loaded into the modified nanoparticles (P(NIPAM-co-AM)-HMSN or PHMSN). The analysis of the microstructure, composition, and temperature-responsibility of the drug-loaded particles were performed using SEM, TEM, TG, BET analysis, FTIR, UV-Vis spectroscopy, etc. Blending PCL with drug-loaded PHMSN, a composite fibrous membrane (CIP@PHMSN-PCL) was fabricated using electrospinning. CIP@PHMSN-PCL exhibited temperature-stimulated drug releasing, with cumulative release rates of CIP reaching 90.78% and 72.67% at 45℃ and 25℃ after 72 hours, respectively. The Korsmeyer-Peppas model aptly described the drug release kinetics, suggesting the diffusion as the primary mechanisms for drug release from the composite fiber membrane. At 45℃, the drug-loaded fiber membrane exhibited a 100% inhibition rate against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). At 25℃, the inhibition rates were 92.34% and 95.83% against E. coli and S. aureus, respectively, demonstrating temperature-dependent drug release performance of the CIP@PHMSN-PCL membrane. In summary, the drug-loaded PHMSN composite nanofiber membrane exhibits temperature-regulated drug release functionality and excellent antibacterial activity, holding potential application value in the biomedical field.
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Key words:
- hollow mesoporous silica /
- thermosensitive /
- nanofiber membrane /
- drug release /
- antibacterial
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图 1 中空介孔二氧化硅纳米颗粒(HMSN)的SEM图(a)和TEM图(b)
Figure 1. SEM image (a) and TEM image (b) of hollow mesoporous silica nanoparticles (HMSN)
图 2 HMSN的FTIR光谱图(a)氮气吸脱附等温线和孔径分布图(b)
Figure 2. FTIR spectrum of HMSN (a) Nitrogen adsorption-desorption isotherm and pore size distribution (b)
图 3 HMSN和共聚物改性HMSN(PHMSN)的FTIR图(a)和TGA(b)图；HMSN(c)和PHMSN(d)的XPS图
Figure 3. FTIR images (a) and TGA images (b) of HMSN and copolymer modification HMSN (PHMSN); XPS images of HMSN (c) and PHMSN (d)
图 4 HMSN(a)和PHMSN(b)的动态光散射(DLS)分析图；HMSN和PHMSN的SAXD图(c)PHMSN的SEM图(插入图为TEM图)(d)
Figure 4. Dynamic light scattering (DLS) analysis images of HMSN (a) and PHMSN (b); SAXD images of HMSN and PHMSN (c) SEM image of PHMSN (the inserted image is a TEM image) (d)
图 5 药物与PHMSN的质量比对包封率(a)载药率(b)和影响
Figure 5. Effect of mass ratio of drug and PHMSN on encapsulation efficiency (a) and drug loading efficiency (b)
图 6 两种温度下环丙沙星(CIP)@HMSN和CIP@PHMSN的释药累积量曲线(a)和CIP@PHMSN动力学拟合曲线(b)
Figure 6. Drug release cumulative curves (a) of ciprofloxacin (CIP)@HMSN and CIP@PHMSN and the kinetic fitting curve (b) of CIP@PHMSN at two temperatures
图 7 PCL纤维膜和CIP@PHMSN-PCL纤维膜的FTIR图(a)；PCL纤维膜的SEM图(b)；CIP@PHMSN-PCL纤维膜的SEM图(c)和TEM图(d)
Figure 7. FTIR image (a) of PCL fiber membrane and CIP@PHMSN-PCL fiber membrane; SEM image (b) of PCL fiber membrane; SEM image (c) and TEM image (d) of CIP@PHMSN-PCL fiber membrane
图 8 不同温度下纤维膜的释药释药累积量曲线(a)以及动力学拟合(b)
Figure 8. Drug release cumulative curves (a) and kinetic fitting (b) of fiber membranes at different temperatures
图 9 不同纤维膜对E. coli(a)和S. aureus(b)的抑菌率
Figure 9. Antibacterial rates of different fiber membranes against E. coli (a) and S. aureus (b)
表 1 25℃下纤维膜的释药累积量动力学拟合
Table 1. Kinetic fitting of cumulative drug release from fiber membrane at 25℃
Model Equation R2 First-Order Model Mt=59.07(1-e−0.13 t) 0.812 Zero-Order Model Mt=0.79t+20.54 0.862 Higuchi Model Mt=1.58(t1/2)+20.54 0.849 Korsmeyer-Peppas Model Mt=17.24(t0.324) 0.980 Notes：t is the time of release; Mt is the amount of drug released at time t; R2 is the regression coefficients. 
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表 2 45℃下纤维膜的释药累积量动力学拟合
Table 2. Kinetic fitting of cumulative drug release from fiber membrane at 45℃
Model Equation R2 First-Order Model Mt=78.66 (1-e−0.11 t) 0.848 Zero-Order Model Mt=1.04t+26.05 0.869 Higuchi Model Mt=2.09(t1/2)+26.04 0.858 Korsmeyer-Peppas Model Mt=21.57(t0.434) 0.991
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