PDF(Pubmed)
Abstract：
Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. STATEMENT OF SIGNIFICANCE: The porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.
摘要：
低分子量亲水性药物的控释，当地管理,允许在目标部位维持高浓度，减少全身副作用，并提高患者的依从性。可注射的水凝胶通常用作载体。然而,低分子量亲水性药物的缓释很难实现,主要是由于药物快速扩散出药物递送系统。在这里，我们提出了一种完全基于脂质体自组装的可注射和自修复水凝胶。脂质体的凝胶化，在不损害其结构完整性的情况下，通过改变胆固醇含量和表面电荷诱导。小的亲水分子，荧光素钠，将其装载在脂质体外空间内或包封到脂质体的水性核心中。这种封装策略能够实现受控和可调的释放曲线，取决于凝胶的机械强度。水凝胶具有高的机械强度，最小的肿胀，缓慢降解。脂质体基水凝胶具有延长的体内机械稳定性,且无局部不良反应。这项工作提出了一类新的可注射水凝胶，有望作为通用的药物递送系统。重要性声明：水凝胶的多孔性对递送小型亲水性药物提出了挑战，通常导致初始爆发释放并缩短释放持续时间。这个问题对于物理交联的水凝胶尤其明显，因为它们的基质可以迅速膨胀和消散，但即使在水凝胶中的聚合物是共价交联的情况下，小分子可以通过其多孔网快速释放。在这里，我们提出了一种完全基于脂质体自组装的可注射自修复水凝胶。小的亲水分子被截留在脂质体外空间内或加载到脂质体的水性核心中，允许控制和可调的释放配置文件。
