Hayward Stephen L, Francis David M, Sis Matthew J, Kidambi Srivatsan
Department of Chemical and Biomolecular Engineering, University of Nebraska-Lincoln, NE, 68588.
Nebraska Center for Materials and Nanoscience, University of Nebraska-Lincoln, NE, 68588.
Sci Rep. 2015 Oct 1;5:14683. doi: 10.1038/srep14683.
The ability to control the spatial distribution and temporal release of a therapeutic remains a central challenge for biomedical research. Here, we report the development and optimization of a novel substrate mediated therapeutic delivery system comprising of hyaluronic acid covalently functionalized liposomes (HALNPs) embedded into polyelectrolyte multilayer (PEM) platform via ionic stabilization. The PEM platform was constructed from sequential deposition of Poly-L-Lysine (PLL) and Poly(Sodium styrene sulfonate) (SPS) "(PLL/SPS)4.5" followed by adsorption of anionic HALNPs. An adsorption affinity assay and saturation curve illustrated the preferential HALNP deposition density for precise therapeutic loading. (PLL/SPS)2.5 capping layer on top of the deposited HALNP monolayer further facilitated complete nanoparticle immobilization, cell adhesion, and provided nanoparticle confinement for controlled linear release profiles of the nanocarrier and encapsulated cargo. To our knowledge, this is the first study to demonstrate the successful embedment of a translatable lipid based nanocarrier into a substrate that allows for temporal and spatial release of both hydrophobic and hydrophilic drugs. Specifically, we have utilized our platform to deliver chemotherapeutic drug Doxorubicin from PEM confined HALNPs. Overall, we believe the development of our HALNP embedded PEM system is significant and will catalyze the usage of substrate mediated delivery platforms in biomedical applications.
控制治疗剂的空间分布和时间释放能力仍然是生物医学研究的核心挑战。在此，我们报告了一种新型底物介导的治疗递送系统的开发和优化，该系统由通过离子稳定作用嵌入聚电解质多层（PEM）平台的共价功能化透明质酸脂质体（HALNP）组成。PEM平台由聚-L-赖氨酸（PLL）和聚（苯乙烯磺酸钠）（SPS）“(PLL/SPS)4.5”的顺序沉积构建而成，随后吸附阴离子型HALNP。吸附亲和力测定和饱和曲线表明了用于精确治疗负载的优先HALNP沉积密度。沉积的HALNP单层顶部的(PLL/SPS)2.5封端层进一步促进了纳米颗粒的完全固定、细胞粘附，并为纳米载体和封装货物的受控线性释放曲线提供了纳米颗粒限制。据我们所知，这是第一项证明将可转化的脂质基纳米载体成功嵌入允许疏水性和亲水性药物进行时空释放的底物的研究。具体而言，我们利用我们的平台从PEM限制的HALNP中递送化疗药物阿霉素。总体而言，我们认为我们的HALNP嵌入PEM系统的开发具有重要意义，并将促进底物介导的递送平台在生物医学应用中的使用。
