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载有抗炎细胞穿透肽的两亲性聚(NIPAm-MBA-AMPS)胶态纳米粒子作为血液相容性载体

Hemocompatible poly(NIPAm-MBA-AMPS) colloidal nanoparticles as carriers of anti-inflammatory cell penetrating peptides.

机构信息

Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, USA.

出版信息

Biomacromolecules. 2012 Apr 9;13(4):1204-11. doi: 10.1021/bm300173x. Epub 2012 Mar 27.

Abstract

Anionic copolymer systems containing sulfated monomers have great potential for delivery of cationic therapeutics, but N-isopropylacrylamide (NIPAm) 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) copolymer nanoparticles have seen limited characterization to date with regard to physical properties relevant to loading and release of therapeutics. Characterization of polymeric nanoparticles incorporating AMPS showed an increased size and decreased thermodynamic swelling ratios of AMPS containing particles as compared to NIPAm nanoparticles lacking AMPS. Particles with increasing AMPS addition showed an increased propensity for uniformity, intraparticle colloidal stability, and drug loading capacity. Peptide encapsulated in particles was shielded from peptide degradation in serum. Particles were shown not impede blood coagulation or to cause hemolysis. This study has demonstrated that AMPS incorporation into traditional NIPAm nanoparticles presents a tunable parameter for changing particle LCST, size, swelling ratio, ζ potential, and cationic peptide loading potential. This one-pot synthesis results in a thermosensitive anionic nanoparticle system that is a potentially useful platform to deliver cationic cell penetrating peptides.

摘要

含磺酸基单体的阴离子共聚物系统在阳离子治疗药物的递送上具有巨大的潜力,但 N-异丙基丙烯酰胺(NIPAm)2-丙烯酰胺基-2-甲基-1-丙磺酸(AMPS)共聚物纳米粒子在与治疗药物的负载和释放相关的物理性质方面的特征描述有限。对含有 AMPS 的聚合物纳米粒子的特征描述表明,与不含 AMPS 的 NIPAm 纳米粒子相比,含有 AMPS 的粒子的粒径增大,热力学溶胀比减小。随着 AMPS 添加量的增加,粒子的均匀性、粒子内胶体稳定性和载药能力呈增加趋势。包封在粒子中的肽在血清中免受肽降解的影响。粒子不会阻碍血液凝固或引起溶血。本研究表明,将 AMPS 掺入传统的 NIPAm 纳米粒子中,为改变粒子的 LCST、粒径、溶胀比、ζ 电位和阳离子肽负载能力提供了一个可调参数。这种一锅合成得到了一种热敏性阴离子纳米粒子系统,是一种潜在有用的阳离子细胞穿透肽递送平台。

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