Department of Drug Chemistry and Technologies, 'Sapienza' University of Rome, Place le A. Moro 5, 00185 Rome, Italy.
Acta Biomater. 2010 Sep;6(9):3657-64. doi: 10.1016/j.actbio.2010.03.013. Epub 2010 Mar 11.
The system described in this paper was obtained by soaking calcium alginate (CaAlg) microspheres in a water solution of poly-[(3-acrylamidopropyl)-trimethylammonium chloride-b-N-isopropylacrylamide] [poly(AMPTMA-b-NIPAAM)], a new block co-polymer recently synthesized by atom transfer radical polymerization (ATRP). The block co-polymer is characterized by a lower critical solution temperature (LCST) of 41 degrees C in aqueous 0.1 M NaCl solution, and can be anchored on the CaAlg microspheres by means of polyion interactions. Polycations (permanently positively charged blocks) and polyanions (free alginate carboxylic groups) interact, leading to microspheres with thermosensitive properties. As an effect of interaction with the microspheres the LCST of the co-polymer is lowered to 36-38 degrees C. In this temperature range a colloidal water suspension of the microspheres collapses, forming macroscopic aggregates. The new system shows, at human body temperature, an improved ability to carry and deliver both hydrophobic and hydrophilic molecules in comparison with unmodified CaAlg microspheres. The release properties of the microspheres loaded with different model drugs can be appropriately modulated by the amount of the poly(AMPTMA-b-NIPAAM). Furthermore, the microspheres show the interesting capability of retaining the activity of a loaded enzyme (horseradish peroxidase), used as a model protein. The results obtained indicate that the proposed drug delivery system may be suitable for drug depot applications.
本文所述系统是通过将海藻酸钠（CaAlg）微球浸泡在聚[（3-丙烯酰胺丙基）-三甲基氯化铵-b-N-异丙基丙烯酰胺] [聚（AMPTMA-b-NIPAAM）]的水溶液中获得的，这是一种最近通过原子转移自由基聚合（ATRP）合成的新型嵌段共聚物。嵌段共聚物在 0.1 M NaCl 水溶液中的低临界溶解温度（LCST）为 41°C，并且可以通过聚离子相互作用锚定在 CaAlg 微球上。聚阳离子（永久带正电荷的嵌段）和聚阴离子（游离海藻酸盐羧酸基团）相互作用，导致微球具有热敏性。作为与微球相互作用的结果，共聚物的 LCST 降低至 36-38°C。在该温度范围内，微球的胶体水悬浮液塌缩，形成宏观聚集体。与未改性的 CaAlg 微球相比，新系统在人体温度下显示出携带和输送疏水分子和亲水分子的能力得到改善。通过共聚物的量可以适当调节载有不同模型药物的微球的释放性能。此外，微球显示出保留负载酶（辣根过氧化物酶）活性的有趣能力，用作模型蛋白。所得结果表明，所提出的药物输送系统可能适用于药物储存库应用。
