Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), (UNLP, CONICET), Sucursal 4, Casilla de Correo 16, 1900 La Plata, Argentina.
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), (UNLP, CONICET), Sucursal 4, Casilla de Correo 16, 1900 La Plata, Argentina.
Colloids Surf B Biointerfaces. 2020 Jun;190:110895. doi: 10.1016/j.colsurfb.2020.110895. Epub 2020 Feb 22.
Multistage delivery systems with size reduction capacity have been proposed as a powerful strategy for improving tissue drug penetration. Here we developed a simple and fast supramolecular approach to construct size-shrinkable polyamine-salt aggregates by ionic cross-linking of biodegradable poly-L-lysine dendrigraft with tripolyphosphate anion. The use of a peptide dendrimer as a nanobuilding block (∼7 nm in diameter) allows the formation of supraparticles (SPs) with well-defined dimensions (∼200 nm in diameter), narrow size distribution and great capacity to encapsulate different molecules, including chemotherapeutic agents as Curcumin and Doxorubicin. When exposed to slightly acidic environments, the crosslinked matrix is instantaneously disassembled to free dendrimer units. Subsequently, model cargo molecules entrapped in the dendrimer architecture can be released by the action of trypsin enzyme through peptide biodegradation. Therefore, these SPs with proved sequential pH and enzyme-responsiveness could be exploited as nanocarriers in multistage drug delivery systems.
具有尺寸减小能力的多阶段递药系统已被提出作为提高组织药物渗透的有力策略。在这里，我们开发了一种简单快速的超分子方法，通过可生物降解的聚-L-赖氨酸树枝状大分子与三磷酸阴离子的离子交联来构建尺寸可收缩的聚胺-盐聚集体。使用肽树枝状大分子作为纳米构建块（直径约为 7nm），可以形成具有明确定义尺寸（直径约为 200nm）、窄尺寸分布和封装不同分子的能力，包括化疗药物如姜黄素和阿霉素。当暴露于略酸性环境时，交联基质会立即分解为游离的树枝状大分子单元。随后，通过肽降解，通过胰蛋白酶酶的作用可以释放包裹在树枝状大分子结构中的模型货物分子。因此，这些具有证明的顺序 pH 值和酶响应性的 SPs 可以被用作多阶段药物递药系统中的纳米载体。
