Cationic cellulose hydrogels:: kinetics of the cross-linking process and characterization as pH-/ion-sensitive drug delivery systems
Cationic cellulose hydrogels:: kinetics of the cross-linking process and characterization as pH-/ion-sensitive drug delivery systems
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DOI：
10.1016/s0168-3659(02)00410-8
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发表时间：
2003-01-17
影响因子：
10.8
通讯作者：
Concheiro, A
中科院分区：
文献类型：
--
作者：
Rodríguez, R;Alvarez-Lorenzo, C;Concheiro, A
通过对形成网络的流变分析，对两种不同羟乙基和铵基含量的阳离子羟乙基纤维素聚季铵盐-4 (PQ-4) 和聚季铵盐-10 (PQ-10) 与乙二醇二缩水甘油醚 (EGDE) 的交联过程进行了表征和优化。研究了NaOH浓度、温度和EGDE浓度对交联速率的影响。在固定角频率下进行的时间扫描实验中记录的弹性 (G') 和粘性 (G") 模量的演变表明，交联剂至少需要 0.05 M NaOH 和 30°C 才能激活。G' 和 G" 的增加遵循一级动力学，G' 的斜率高于与 G" 对应的斜率。凝胶时间，即 G' 和 G" 交叉的时间当温度从 30 摄氏度升高到 60 摄氏度时，该现象呈指数下降。根据凝胶时间估计，表观活化能在 70 至 90 kJ/mol 之间。 PQ-4 的交联速率高于 PQ-10，因为前者的初始粘度较低且羟乙基含量较高。然而，最终水凝胶的红外光谱表明，两种聚合物体系中形成了相似数量的交联结。水凝胶制备的最佳条件是在0.10 M NaOH介质中60℃，并且没有观察到解聚。这种水凝胶是透明的，具有光滑、连续的表面，并且对水具有超强的吸水性。烘箱干燥后，溶胀程度低于新制备的水凝胶；吸水行为是菲克式的。水凝胶具有显着的双氯芬酸钠负载能力，它们通过离子键和疏水键与双氯芬酸钠相互作用。亲和力保持在酸性pH下，防止药物释放。相反，在 pH 8 时，相互作用被破坏，释放过程持续超过 4 小时。结果还表明，当评估释放时将pH值从酸性切换为碱性时，离子强度以及介质的初始pH值是两个关键因素，必须考虑这两个因素才能得出关于水凝胶作为体内条件下位点特异性递送系统的行为的结论。 (C) 2002 Elsevier Science B.V. 保留所有权利。
The cross-linking process of two cationic hydroxyethylcelluloses of different hydroxyethyl and ammonium group contents, polyquaternium-4 (PQ-4) and polyquaternium-10 (PQ-10), with ethylenglycol diglycidylether (EGDE) was characterized and optimized through rheometric analysis of the forming network. The influence of NaOH concentration, temperature, and EGDE concentration on the cross-linking rate were studied. The evolution of the elastic (G') and viscous (G") moduli, recorded in time-sweep experiments carried out at a fixed angular frequency, showed that the cross-linker requires a minimum of 0.05 M NaOH and 30 degreesC to be active. The increase in G' and G" followed first order kinetics, the slopes of G' being higher than those corresponding to G". The gel time, i.e. the time at which the crossover of G' and G" occurs, decreases exponentially when temperature increases from 30 to 60 degreesC. Apparent activation energies, estimated from the gel times, ranged between 70 and 90 kJ/mol. The cross-linking rate was greater in PQ-4 than in PQ-10 owing to the initial lower viscosity and higher content in hydroxyethyl groups of the former. However, IR spectra of the final hydrogels suggest the formation of a similar number of cross-linking junctions in both polymer systems. The optimum conditions for hydrogel preparation were 60 degreesC in 0.10 M NaOH medium, and no depolymerization was observed. Such hydrogels were transparent, presented a smooth, continuous surface, and were superabsorbent in water. After drying in an oven, the degree of swelling was lower than that of freshly prepared hydrogels; the behavior of water uptake being Fickian. The hydrogels presented a significant loading capacity of diclofenac sodium, with which they interact through ionic and hydrophobic bonding. The affinity is kept at an acidic pH, preventing drug release. In contrast, at pH 8 the interactions are broken and the release process is sustained for more than 4 h. The results also indicate that the ionic strength as well as the initial pH of the medium, when the release was evaluated switching the pH from acidic to basic, are two critical factors which have to be considered to extract conclusions about the behavior of the hydrogels as site-specific delivery systems under in vivo conditions. (C) 2002 Elsevier Science B.V. All rights reserved.