Laboratory for Biomaterials and Drug Delivery, Boston Children's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA; Department of Anesthesiology, Critical Care, and Pain Management, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Laboratory for Biomaterials and Drug Delivery, Boston Children's Hospital, Harvard Medical School, Harvard Institutes of Medicine, Boston, MA 02115, USA; Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Acta Biomater. 2024 Jul 15;183:101-110. doi: 10.1016/j.actbio.2024.05.044. Epub 2024 Jun 2.
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.
局部给予低分子量亲水性药物的控制释放可使靶位维持高浓度，减少全身副作用，并提高患者顺应性。可注射水凝胶通常用作载体。然而，低分子量亲水性药物的缓慢释放非常困难，主要是由于药物从药物输送系统中迅速扩散。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。通过改变胆固醇含量和表面电荷来诱导脂质体凝胶化，而不会破坏其结构完整性。将小亲水分子，如荧光素钠，加载到脂质体的额外腔室中或封装到脂质体的水核中。这种封装策略使我们能够实现依赖于凝胶机械强度的可控和可调的释放曲线。该水凝胶具有较高的机械强度、最小的溶胀和缓慢的降解。基于脂质体的水凝胶在体内具有较长的机械稳定性和良性组织反应。这项工作提出了一种新型的可注射水凝胶，作为一种多功能药物输送系统具有广阔的前景。
水凝胶的多孔性质给输送小亲水性药物带来了挑战，通常导致初始突释和释放时间缩短。对于物理交联的水凝胶来说，这个问题尤其明显，因为其基质会迅速膨胀和消散，但即使在水凝胶中的聚合物是通过共价交联的情况下，小分子也可以通过其多孔网格迅速释放。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。将小亲水分子包埋在脂质体的额外腔室中或加载到脂质体的水核中，实现了可控和可调的释放曲线。
