Bromberg Lev
Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA 02139, USA.
Expert Opin Drug Deliv. 2005 Nov;2(6):1003-13. doi: 10.1517/17425247.2.6.1003.
A novel approach toward improvements of oral chemotherapeutic formulations has evolved, which combines solubilisation (molecular dispersion) of the hydrophobic anticancer drugs in micelles attached to large macromolecules or microparticles. The large size of the macromolecules or microgels prevents the gel components from being transported into the systemic circulation. The discussed gels comprise copolymers of poly(acrylic acid) (PAA) and Pluronic surfactants, linked via C-C bonds. The Pluronic-PAA copolymers are non-irritating when administered orally. The micelles formed in the Pluronic-PAA solutions and in crosslinked microgels can be loaded with chemotherapeutic drugs and then released in contact with the intestine. The microgels are collapsed at the acidic pH of the stomach and expand, thus releasing the loaded drugs at the pH of the lower gastrointestinal tract. Yet the microgels are mucoadhesive and enable longer retention time and prolonged release in the colon. Ease of preparation and formulation of the drugs with the Pluronic-PAA polymers and gels may enable the wider use of oral chemotherapy, resulting in a better patient compliance and improved quality of life of the patients.
一种改进口服化疗制剂的新方法已经出现，它将疏水性抗癌药物在附着于大分子或微粒的胶束中增溶（分子分散）。大分子或微凝胶的大尺寸可防止凝胶成分进入体循环。所讨论的凝胶包含通过C-C键连接的聚丙烯酸（PAA）和普朗尼克表面活性剂的共聚物。口服给药时，普朗尼克-PAA共聚物无刺激性。在普朗尼克-PAA溶液和交联微凝胶中形成的胶束可以装载化疗药物，然后在与肠道接触时释放。微凝胶在胃的酸性pH值下会塌陷并膨胀，从而在胃肠道下部的pH值下释放所装载的药物。然而，微凝胶具有粘膜粘附性，能够在结肠中保持更长的保留时间并实现延长释放。使用普朗尼克-PAA聚合物和凝胶制备和配制药物的简便性可能使口服化疗得到更广泛的应用，从而提高患者的依从性并改善患者的生活质量。
