Hatton Fiona L, Tatham Lee M, Tidbury Louise R, Chambon Pierre, He Tao, Owen Andrew, Rannard Steven P
Department of Chemistry , University of Liverpool , Crown Street , L69 7ZD , UK . Email:
Department of Molecular and Clinical Pharmacology , University of Liverpool , Block H, 70 Pembroke Place , Liverpool L69 3GF , UK.
Chem Sci. 2015 Jan 1;6(1):326-334. doi: 10.1039/c4sc02889a. Epub 2014 Oct 3.
The development of nanomaterials for advanced therapies requires the formation of versatile platforms that may be tuned to maximize beneficial attributes and minimize unwanted negative behaviour. Additionally, the optimum route of administration is a key consideration of any new treatment and much work has been focused on direct injection into the systemic circulation rather than oral delivery. Here we describe a new approach to polymeric nanoparticle design and present initial results showing the potential for tuneable permeation through a gut epithelium model. Through the use of mixed initiators and branched vinyl polymerization, a series of systematically varying branched polymers have been synthesized and nanoprecipitated. The surprisingly uniform structures have undergone preliminary pharmacological evaluation to establish low cytotoxicity and enhanced permeation through model intestinal epithelial cells. This presents potential opportunities for future developments that may allow oral dosing to result in circulating polymeric nanoparticles; behaviour that may prove clinically desirable to many non-terminal or chronic diseases that utilise nanomedicines but wish to avoid regular or repeated intravenous administration.
用于先进疗法的纳米材料的开发需要形成多功能平台,这些平台可以进行调整,以最大限度地发挥有益特性,并将不良负面行为降至最低。此外,最佳给药途径是任何新疗法的关键考虑因素,并且许多工作都集中在直接注入体循环而非口服给药上。在此,我们描述了一种聚合物纳米颗粒设计的新方法,并展示了初步结果,这些结果表明通过肠道上皮模型实现可调节渗透的潜力。通过使用混合引发剂和支化乙烯基聚合,合成了一系列系统变化的支化聚合物并进行了纳米沉淀。这些令人惊讶的均匀结构已经过初步药理学评估,以确定其低细胞毒性和通过模型肠上皮细胞的增强渗透。这为未来的发展提供了潜在机会,未来可能使口服给药产生循环聚合物纳米颗粒;对于许多使用纳米药物但希望避免定期或重复静脉注射的非终末期或慢性疾病来说,这种行为在临床上可能是可取的。