PDF(Pubmed)
Abstract：
Nanotherapeutics have gained significant attention for the treatment of numerous cancers, primarily because they can accumulate in and/or selectively target tumors leading to improved pharmacodynamics of encapsulated drugs. The flexibility to engineer the nanotherapeutic characteristics including size, morphology, drug release profiles, and surface properties make nanotherapeutics a unique platform for cancer drug formulation. Polymeric nanotherapeutics including micelles and dendrimers represent a large number of formulation strategies developed over the last decade. However, compared to liposomes and lipid-based nanotherapeutics, polymeric nanotherapeutics have had limited clinical translation from the laboratory. One of the key limitations of polymeric nanotherapeutics formulations for clinical translation has been the reproducibility in preparing consistent and homogeneous large-scale batches. In this review, we describe polymeric nanotherapeutics and discuss the most common laboratory and scale-up formulation methods, specifically those proposed for clinical cancer therapies. We also provide an overview of the major challenges and opportunities for scaling polymeric nanotherapeutics to clinical-grade formulations. Finally, we will review the regulatory requirements and challenges in advancing nanotherapeutics to the clinic.
摘要：
纳米疗法在治疗许多癌症方面获得了极大的关注，主要是因为它们可以在肿瘤中积累和/或选择性靶向肿瘤,导致包封药物的药效学改善。设计纳米治疗特性的灵活性，包括尺寸，形态学,药物释放概况，和表面特性使纳米治疗成为癌症药物配方的独特平台。包括胶束和树枝状聚合物的聚合物纳米治疗剂代表了过去十年中开发的大量制剂策略。然而,与脂质体和基于脂质的纳米治疗剂相比，聚合物纳米疗法在实验室中的临床翻译有限。用于临床翻译的聚合物纳米治疗剂制剂的关键限制之一是制备一致且均匀的大规模批次的再现性。在这次审查中,我们描述了聚合物纳米疗法，并讨论了最常见的实验室和放大制剂方法，特别是那些建议临床癌症治疗。我们还概述了将聚合物纳米治疗剂扩展到临床级制剂的主要挑战和机遇。最后,我们将回顾将纳米疗法推向临床的监管要求和挑战。
