Eloy Josimar Oliveira, Claro de Souza Marina, Petrilli Raquel, Barcellos Juliana Palma Abriata, Lee Robert J, Marchetti Juliana Maldonado
College of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Avenida do Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil; College of Pharmacy, The Ohio State University, Columbus, 500 W 12th Ave, Columbus, OH 43210, United States.
College of Pharmaceutical Sciences of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Avenida do Cafe s/n, 14040-903 Ribeirao Preto, SP, Brazil.
Colloids Surf B Biointerfaces. 2014 Nov 1;123:345-63. doi: 10.1016/j.colsurfb.2014.09.029. Epub 2014 Sep 22.
Although hydrophilic small molecule drugs are widely used in the clinic, their rapid clearance, suboptimal biodistribution, low intracellular absorption and toxicity can limit their therapeutic efficacy. These drawbacks can potentially be overcome by loading the drug into delivery systems, particularly liposomes; however, low encapsulation efficiency usually results. Many strategies are available to improve both the drug encapsulation efficiency and delivery to the target site to reduce side effects. For encapsulation, passive and active strategies are available. Passive strategies encompass the proper selection of the composition of the formulation, zeta potential, particle size and preparation method. Moreover, many weak acids and bases, such as doxorubicin, can be actively loaded with high efficiency. It is highly desirable that once the drug is encapsulated, it should be released preferentially at the target site, resulting in an optimal therapeutic effect devoid of side effects. For this purpose, targeted and triggered delivery approaches are available. The rapidly increasing knowledge of the many overexpressed biochemical makers in pathological sites, reviewed herein, has enabled the development of liposomes decorated with ligands for cell-surface receptors and active delivery. Furthermore, many liposomal formulations have been designed to actively release their content in response to specific stimuli, such as a pH decrease, heat, external alternating magnetic field, ultrasound or light. More than half a century after the discovery of liposomes, some hydrophilic small molecule drugs loaded in liposomes with high encapsulation efficiency are available on the market. However, targeted liposomes or formulations able to deliver the drug after a stimulus are not yet a reality in the clinic and are still awaited.
尽管亲水性小分子药物在临床上广泛应用，但其快速清除、生物分布欠佳、细胞内吸收低以及毒性等问题会限制其治疗效果。将药物载入递送系统，尤其是脂质体，有可能克服这些缺点；然而，通常会导致包封效率较低。有许多策略可用于提高药物包封效率以及将药物递送至靶部位以减少副作用。对于包封而言，有被动和主动策略。被动策略包括正确选择制剂的组成、zeta电位、粒径和制备方法。此外，许多弱酸和弱碱，如阿霉素，能够被高效主动载入。非常希望药物一旦被包封，应优先在靶部位释放，从而产生无副作用的最佳治疗效果。为此，有靶向和触发递送方法。本文综述了病理部位许多过表达的生化标志物的知识迅速增加，这使得能够开发用细胞表面受体配体修饰的脂质体以及主动递送。此外，许多脂质体制剂被设计成能响应特定刺激，如pH降低、热、外部交变磁场、超声或光，而主动释放其内容物。在脂质体发现半个多世纪后，一些高包封效率载入脂质体的亲水性小分子药物已上市。然而，靶向脂质体或能够在刺激后递送药物的制剂在临床上尚未成为现实，仍有待实现。
