Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612-7231, USA.
J Control Release. 2012 Oct 10;163(1):34-45. doi: 10.1016/j.jconrel.2012.06.002. Epub 2012 Jun 12.
Drug toxicity is an important factor that contributes significantly to adverse drug events in current healthcare practice. Application of lipid-based nanocarriers in drug formulation is one approach to improve drug safety. Lipid-based delivery systems include micelles, liposomes, solid lipid nanoparticles, nanoemulsions and nanosuspensions. These carriers are generally composed of physiological lipids well tolerated by human body. Delivery of water-insoluble drugs in these formulations increases their solubility and stability in aqueous media and eliminates the need for toxic co-solvents or pH adjustment to solubilize hydrophobic drugs. Association or encapsulation of peptides/proteins within lipid-based carriers protects the labile biologics against enzymatic degradation, hence reducing the therapeutic dose required and risk of dose-dependent toxicity. Most importantly, lipid-based nanocarriers alter the pharmacokinetics and biodistribution of drugs through passive and active targeting, leading to increased drug accumulation at target sites while significantly decreasing non-specific distribution to other tissues. Furthermore, surface modification of these nanocarriers reduces immunogenicity of drug-carrier complexes, imparts stealth by preventing opsonization and removal by phagocytes and minimizes interaction with circulating blood components. In view of heightening attention on drug safety in patient treatment, lipid-based nanocarrier is therefore an important and promising option for formulation of pharmaceutical products to improve treatment safety and efficacy.
药物毒性是当前医疗实践中导致药物不良事件的一个重要因素。在药物制剂中应用基于脂质的纳米载体是提高药物安全性的一种方法。基于脂质的递药系统包括胶束、脂质体、固体脂质纳米粒、纳米乳剂和纳米混悬剂。这些载体通常由人体能够很好耐受的生理脂质组成。这些制剂中难溶性药物的递运增加了其在水介质中的溶解度和稳定性,且无需使用有毒共溶剂或 pH 值调节来溶解疏水性药物。将肽/蛋白质与基于脂质的载体结合或包封可保护不稳定的生物制剂免受酶降解,从而减少所需的治疗剂量和剂量依赖性毒性的风险。最重要的是,基于脂质的纳米载体通过被动和主动靶向改变药物的药代动力学和生物分布,导致药物在靶部位的蓄积增加,而对其他组织的非特异性分布显著减少。此外,这些纳米载体的表面修饰可降低药物-载体复合物的免疫原性,通过防止被吞噬细胞吞噬和清除来赋予隐形性,并最小化与循环血液成分的相互作用。鉴于人们对患者治疗中药物安全性的关注度日益提高,因此,基于脂质的纳米载体是改善治疗安全性和疗效的药物制剂的一个重要且有前途的选择。