Controled loading and release of model drugs from polyelectrolyte multilayer thin films

The Layer-by-Layer (LbL) self assembly technique of polyelectrolyte multilayers (PEM) has shown great potential in bio-coating material as well as local drug delivery systems. Herein, combination of positively charged polyelectrolyte of poly(diallyldimethylammonium chloride) (PDADMAC) or chitosan (Chi) and negatively charged polyelectrolyte of poly(sodium 4-styrenesulfonate) (PSS) or poly(4-styrene sulfonic acid-co-maleic acid, sodium salt) (PSSMA) were constructed and used as polymer matrix and coatings for control release of various drugs. Structure, thickness, roughness and stability of the PEM films were characterized by uv-vis spectrophotometer and AFM measurement. Model drugs (curcumin, diclofenac sodium and gentian violet) were incorporated in the polymer matrix and their loading and release behavior was quantified by uv-vis spectrophotometer as a function of the external media. The loading of the model drugs was achieve through hydrophobic interaction or electrostatic interaction and controlled by solution media characteristics such as solvent composition, pH, ionic strength but also loading time and number of constructed layers. Differences in polymer matrix structures have been found to influence the loading and release behavior under otherwise fixed conditions. Results indicated that the release of curcumin was affected by changing the solvent composition of water/ethanol and ionic strength while the release of diclofenac sodium and gentian violet was most affected by the pH and ionic strength of the loading medium. The polymer matrix of PDADMAC/PSS, PDADMAC/PSSMA and Chi/PSS can therefore be used as drug reservoir for the controlled loading of functional molecules and their release. In addition, PEM blocking layer deposited on top of polymer matrix were used to prolong the slow release of curcumin from PEM matrix substrates when exposed to physiological buffer. The blocking films was constructed by the LbL self assembly of positively charged of chitosan (Chi) and negatively charged of alginate (Alg) or poly acrylic acid (PAA). Both blocking films delayed the release of curcumin when compared to a PDADMAC/PSS blocking film with the Chi/Alg film being the most efficient. Finally, in an attempt to explore an innovative application of drug loaded PEM films, fruit were coated with PEM films and loaded with curcumin was used to quantify the amount of curcumin loaded at the surface of the fruit.聚电解质多层膜（polyelectrolyte multilayers，PEM）的层层（Layer-by-Layer，LbL）自组装技术在生物涂层材料以及局部药物递送系统领域展现出巨大应用潜力。本研究中，将带正电的聚电解质——聚二烯丙基二甲基氯化铵（poly(diallyldimethylammonium chloride)，PDADMAC）或壳聚糖（chitosan，Chi）——与带负电的聚电解质——聚4-苯乙烯磺酸钠（poly(sodium 4-styrenesulfonate)，PSS）或聚(4-苯乙烯磺酸-共聚-马来酸单钠盐)（poly(4-styrene sulfonic acid-co-maleic acid, sodium salt)，PSSMA）进行复合，构建得到聚合物基质与涂层，用于多种药物的控释。通过紫外-可见分光光度计与原子力显微镜（Atomic Force Microscope，AFM）表征了PEM薄膜的结构、厚度、粗糙度与稳定性。将模型药物（姜黄素、双氯芬酸钠与龙胆紫）负载至聚合物基质中，并以紫外-可见分光光度法定量分析其负载与释放行为，探究其与外部介质的相关性。模型药物的负载通过疏水相互作用或静电相互作用实现，其负载过程受溶液介质特性（如溶剂组成、pH值、离子强度）、负载时间以及所构建的多层膜层数共同调控。研究发现，在其余条件固定的前提下，聚合物基质结构的差异会对药物负载与释放行为产生显著影响。实验结果表明，姜黄素的释放行为受水/乙醇溶剂组成与离子强度的调控，而双氯芬酸钠与龙胆紫的释放行为则主要受负载介质的pH值与离子强度影响。因此，PDADMAC/PSS、PDADMAC/PSSMA以及Chi/PSS型聚合物基质可作为药物储库，用于功能分子的可控负载与释放。此外，在聚合物基质表面沉积的PEM阻隔层，可在置于生理缓冲液中时延缓姜黄素从PEM基质基底中的缓慢释放。该阻隔薄膜通过带正电的壳聚糖（chitosan，Chi）与带负电的海藻酸钠（alginate，Alg）或聚丙烯酸（poly acrylic acid，PAA）的LbL自组装制备得到。与PDADMAC/PSS型阻隔薄膜相比，这两种阻隔薄膜均能延缓姜黄素的释放，其中Chi/Alg型阻隔薄膜的延缓效果最为显著。最后，为探索负载型PEM薄膜的创新应用，将负载有姜黄素的PEM薄膜涂覆于水果表面，并以此定量测定水果表面负载的姜黄素含量。