Reddy L Harivardhan
Drug Delivery Research Laboratory, Center of Relevance and Excellence in NDDS, Pharmacy Department, Fatehgunj, M.S. University of Baroda, Baroda-390002, Gujarat, India.
J Pharm Pharmacol. 2005 Oct;57(10):1231-42. doi: 10.1211/jpp.57.10.0001.
Despite several advancements in chemotherapy, the real therapy of cancer still remains a challenge. The development of new anti-cancer drugs for the treatment of cancer has not kept pace with the progress in cancer therapy, because of the nonspecific drug distribution resulting in low tumour concentrations and systemic toxicity. The main hindrance for the distribution of anti-cancer agents to the tumour site is the highly disorganized tumour vasculature, high blood viscosity in the tumour, and high interstitial pressure within the tumour tissue. Recently, several approaches such as drug modifications and development of new carrier systems for anti-cancer agents have been attempted to enhance their tumour reach. Approaches such as drug delivery through enhanced permeability and retention (EPR) effect have resulted in a significant improvement in concentration in tumours, while approaches such as drug-carrier implants and microparticles have resulted in improvement in local chemotherapy of cancer. This review discusses different strategies employed for the delivery of anti-cancer agents to tumours, such as through EPR effect, local chemotherapeutic approaches using drug delivery systems, and special strategies such as receptor-mediated delivery, pH-based carriers, application of ultrasound and delivery to resistant tumour cells and brain using nanoparticles.
尽管化疗取得了一些进展,但癌症的真正治疗仍然是一项挑战。由于非特异性药物分布导致肿瘤浓度低和全身毒性,用于治疗癌症的新型抗癌药物的开发未能跟上癌症治疗的进展。抗癌药物向肿瘤部位分布的主要障碍是肿瘤血管高度紊乱、肿瘤内血液粘度高以及肿瘤组织内间质压力高。最近,人们尝试了几种方法,如药物修饰和开发新型抗癌药物载体系统,以提高药物到达肿瘤的能力。通过增强渗透和滞留(EPR)效应进行药物递送等方法已使肿瘤中的药物浓度有了显著提高,而药物载体植入和微粒等方法则改善了癌症的局部化疗。本文综述了将抗癌药物递送至肿瘤的不同策略,如通过EPR效应、使用药物递送系统的局部化疗方法,以及受体介导递送、基于pH的载体、超声应用以及使用纳米颗粒递送至耐药肿瘤细胞和脑部等特殊策略。