Department of Engineering and Technology of Chemical Processes, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland.
Department of Physical Chemistry and Materials Science, University of Szeged, Rerrich Béla tér 1, Szeged H-6720, Hungary.
Langmuir. 2022 May 10;38(18):5404-5417. doi: 10.1021/acs.langmuir.1c03360. Epub 2022 Apr 20.
Encapsulation of hydrophilic and amphiphilic drugs in appropriate colloidal carrier systems for sustained release is an emerging problem. In general, hydrophobic bioactive substances tend to accumulate in water-immiscible polymeric domains, and the release process is controlled by their low aqueous solubility and limited diffusion from the nanocarrier matrix. Conversely, hydrophilic/amphiphilic drugs are typically water-soluble and insoluble in numerous polymers. Therefore, a core-shell approach─nanocarriers comprising an internal core and external shell microenvironments of different properties─can be exploited for hydrophilic/amphiphilic drugs. To produce colloidally stable poly(lactic--glycolic) (PLGA) nanoparticles for mitomycin C (MMC) delivery and controlled release, a unique class of amphiphilic polymers─hydrophobically functionalized polyelectrolytes─were utilized as shell-forming materials, comprising both stabilization via electrostatic repulsive forces and anchoring to the core via hydrophobic interactions. Undoubtedly, the use of these polymeric building blocks for the core-shell approach contributes to the enhancement of the payload chemical stability and sustained release profiles. The studied nanoparticles were prepared via nanoprecipitation of the PLGA polymer and were dissolved in acetone as a good solvent and in an aqueous solution containing hydrophobically functionalized poly(4-styrenesulfonic--maleic acid) and poly(acrylic acid) of differing hydrophilic-lipophilic balance values. The type of the hydrophobically functionalized polyelectrolyte (HF-PE) was crucial for the chemical stability of the payload─derivatives of poly(acrylic acid) were found to cause very rapid degradation (hydrolysis) of MMC, in contrast to poly(4-styrenesulfonic--maleic acid). The present contribution allowed us to gain crucial information about novel colloidal nanocarrier systems for MMC delivery, especially in the fields of optimal HF-PE concentrations, appropriate core and shell building materials, and the colloidal and chemical stability of the system.
将亲水性和两亲性药物封装在适当的胶体载体系统中以实现缓释是一个新兴问题。一般来说，疏水性生物活性物质倾向于聚集在与水不混溶的聚合物域中，并且释放过程受其低水溶性和从纳米载体基质中有限扩散的控制。相反，亲水性/两亲性药物通常在水中可溶且不溶于许多聚合物中。因此，可以利用核壳方法——由具有不同性质的内部核和外部壳微环境组成的纳米载体——来负载亲水性/两亲性药物。为了制备用于米托蒽醌（MMC）传递和控制释放的胶体稳定的聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒，利用了一类独特的两亲性聚合物——疏水性官能化聚电解质——作为壳形成材料，既通过静电排斥力进行稳定，又通过疏水性相互作用锚定在核上。毫无疑问，这些聚合物构建块用于核壳方法有助于提高有效载荷的化学稳定性和缓释特性。所研究的纳米颗粒是通过 PLGA 聚合物的纳米沉淀制备的，并溶解在丙酮中作为良溶剂，以及溶解在含有疏水性官能化聚（4-苯乙烯磺酸-马来酸）和聚（丙烯酸）的水溶液中，其亲水性-疏水性平衡值不同。疏水性官能化聚电解质（HF-PE）的类型对有效载荷的化学稳定性至关重要——发现聚丙烯酸衍生物会导致 MMC 非常快速的降解（水解），而聚 4-苯乙烯磺酸-马来酸则不然。本研究使我们能够获得有关 MMC 传递的新型胶体纳米载体系统的关键信息，特别是在最佳 HF-PE 浓度、合适的核和壳构建材料以及系统的胶体和化学稳定性等方面。
