Technical University of Denmark, Departamento of Micro and Nanotechnology, Kgs. Lyngby, Denmark.
J Colloid Interface Sci. 2013 Apr 1;395:58-63. doi: 10.1016/j.jcis.2012.12.052. Epub 2013 Jan 3.
Polymers play a central role in the development of carriers for diagnostic and therapeutic agents. Especially the use of either degradable polymers or porous materials to encapsulate drug compounds in order to obtain steady drug release profiles has received much attention. We present here a proof of principle for a system combining these two encapsulation methods and consisting of a nanoporous polymer (NP) with the pores filled with a degradable polymer mixed with a drug model. Rhodamine 6G (R6G) mixed with Poly(L-Lactic Acid) (PLLA) were confined within the 14 nm pores of a NP with gyroid morphology derived from a diblock copolymer precursor. Glass transition, crystallization and melting of free and confined PLLA were monitored by differential scanning calorimetry. Release profiles for R6G were measured in methanol-water solvents at pH 13, which works as an accelerated release test by speeding up the hydrolysis of PLLA. The obtained release profiles demonstrate that the degradation of PLLA in nanoporous confinement is significantly slower than the degradation of unconfined PLLA. The release of R6G encapsulated in PLLA becomes correspondingly slower, while the initial burst release virtually disappears. These findings suggest that the presented proof of principle constitutes a promising basis for the development of novel implantable drug delivery systems.
聚合物在诊断和治疗试剂载体的开发中起着核心作用。特别是使用可降解聚合物或多孔材料来封装药物化合物,以获得稳定的药物释放曲线,已经引起了广泛关注。我们在这里提出了一个将这两种封装方法结合起来的系统的原理证明,该系统由纳米多孔聚合物(NP)和填充有可降解聚合物与药物模型混合物的多孔材料组成。罗丹明 6G(R6G)与聚(L-乳酸)(PLLA)混合后被限制在具有由两嵌段共聚物前体衍生的准晶形态的 NP 的 14nm 孔内。通过差示扫描量热法监测游离 PLLA 和受限 PLLA 的玻璃化转变、结晶和熔融。在 pH 值为 13 的甲醇-水溶剂中测量 R6G 的释放曲线,这通过加速 PLLA 的水解来进行加速释放测试。所得的释放曲线表明,纳米孔限制中的 PLLA 降解明显比无约束 PLLA 降解慢。包封在 PLLA 中的 R6G 的释放相应地变慢,而初始突释几乎消失。这些发现表明,所提出的原理证明为开发新型可植入药物输送系统提供了有前途的基础。