Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics
Solid Matrix Based Lipidic Nanoparticles in Oral Cancer Chemotherapy: Applications and Pharmacokinetics
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DOI：
10.2174/1389200216666150812122128
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发表时间：
2015-01-01
影响因子：
2.3
通讯作者：
Akhter, Sohail
中科院分区：
文献类型：
--
作者：
Ahmad, Javed;Amin, Saima;Akhter, Sohail
通过口服途径在癌症患者中递送化疗药物具有创造“免住院化疗”的潜力，这是肿瘤学家、制剂科学家和患者的愿景。这种治疗方法将提高患者的依从性，减轻患者照顾者的负担，并大大降低治疗费用。在目前的临床实践中，通过静脉内注射或输注进行的化疗导致不期望的副作用，例如血浆浓度超过最大安全浓度、快速的身体清除和较低的生物利用度。尽管存在诸如药物的水溶性和稳定性差以及胃肠道中存在多药外排转运蛋白等生物屏障等挑战，但口腔癌化疗有可能克服这些障碍。脂质纳米粒（LNP）如固体脂质纳米粒、纳米结构脂质载体、纳米脂质-药物缀合物、混合胶束、脂质体和纳米乳剂已经显示出通过纳米技术方法用于口服抗癌药物递送的一些有希望的结果。LNP表现出增强的口服生物利用度，这是由于其通过乳糜微粒连接的和/或M细胞摄取经由淋巴吸收抑制首过代谢的能力。LNP降低了施用药物的受试者间和受试者内的药代动力学变异性。此外，在LNP制剂中使用的某些类别的磷脂和表面活性剂可以抑制P-糖蛋白流出系统。在这里，我们将讨论口腔癌化疗中的生物制药挑战以及LNP如何为这些挑战提供解决方案。还将讨论胃肠道环境对LNP和药代动力学的影响。
Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter-and intra-subject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed.