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Synthesis and characterisation of cationic quaternary ammonium-modified polyvinyl alcohol hydrogel beads as a drug delivery embolisation system

机译:阳离子季铵改性聚乙烯醇水凝胶微珠的合成与表征

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摘要

To extend the platform of clinically utilised chemoembolic agents based on ion-exchange systems to support the delivery of anionic drugs, a series of PVA-based beads was produced with different levels of (3-acrylamidopropyl)trimethylammonium chloride (APTA) in their formulation. The beads were characterised to confirm composition and the effect of formulation variation on physical properties was assessed. Suspension polymerisation was shown to successfully produce uniformly spherical copolymer beads with APTA content up to 60 wt%. Equilibrium water content and resistance to compression both increased with increasing APTA content in the formulation. Confocal laser scanning microscopy was used with model drugs to demonstrate that by increasing APTA content, compounds between the molecular weight range 70–250 kDa could permeate the microsphere structures. Interaction with anionic drugs was modelled using multivalent dyes. Dyes with multi-binding sites had increased interaction with the polymer, slowing the release and also demonstrating a reduced rate of elution from beads with higher charge density. The model drug release studies demonstrate that these systems can be engineered for different potential anionic drugs for local therapeutic delivery in the clinic.
机译:为了扩展基于离子交换系统的临床使用的化学栓塞剂的平台以支持阴离子药物的输送,生产了一系列基于PVA的珠,其配方中含有不同含量的(3-丙烯酰胺基丙基)三甲基氯化铵(APTA)。表征珠粒以确认组成,并评估制剂变化对物理性质的影响。悬浮聚合已显示成功生产出APTA含量高达60 wt%的均匀球形共聚物珠粒。平衡水含量和抗压缩性均随配方中APTA含量的增加而增加。共聚焦激光扫描显微镜与模型药物一起使用证明,通过增加APTA含量,分子量范围在70-250 kDa之间的化合物可以渗透微球结构。使用多价染料模拟与阴离子药物的相互作用。具有多结合位点的染料与聚合物的相互作用增加,减慢了释放速度,还显示出电荷密度较高的珠子洗脱速度降低。模型药物释放研究表明,这些系统可针对不同的潜在阴离子药物进行工程改造,以在临床上进行局部治疗。

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