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首页> 外文期刊>BMC Biotechnology >Microbial synthesized biodegradable PHBHHxPEG hybrid copolymer as an efficient intracellular delivery nanocarrier for kinase inhibitor
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Microbial synthesized biodegradable PHBHHxPEG hybrid copolymer as an efficient intracellular delivery nanocarrier for kinase inhibitor

机译：微生物合成的可生物降解的PHBHHxPEG杂化共聚物作为激酶抑制剂的有效细胞内递送纳米载体

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Background Protein Kinases are key regulators of cell function and play essential roles in the occurrence and development of many human diseases. Many kinase inhibitors have been used for molecular targeted treatment of those diseases such as cancer and inflammation. However, those highly hydrophobic kinase inhibitors shared the common features of poor bioavailability and limited in vivo half-life, which strongly impeded their practical applications. Our previous study demonstrated that microbial synthesized biodegradable polyester poly(3-hydroxybutyrate- co -3-hydroxyhexanoate) (PHBHHx), a member of polyhydroxyalkanoates (PHAs) family, could serve as a promising delivery nanocarrier for those hydrophobic kinase inhibitors. Recently, a novel natural synthesized hybrid copolymer, PEG200 end-capped PHBHHx (PHBHHxPEG) was produced by Aeromonas hydrophila fermentation. In this study, the novel PHBHHxPEG NPs were prepared and investigated to serve as intracellular delivery nanocarriers for sustained release of hydrophobic kinase inhibitors. Results PHBHHxPEG nanoparticles (NPs) prepared by an emulsification–solvent evaporation method were spherical with a diameter around 200?nm. The entrapment efficiency on rapamycin in PHBHHxPEG NPs was 91.9% and the sustained release of rapamycin from PHBHHxPEG NPs could be achieved for almost 10 days. The cellular uptake of PHBHHxPEG NPs was significant higher than that of PHBHHx NPs. The anti-proliferation effect and mTOR inhibition ability of rapamycin-loaded PHBHHxPEG NPs was stronger than that of drug-loaded PHBHHx NPs and free rapamycin. Conclusions PHBHHxPEG NPs could achieve the efficient entrapment and sustained release of rapamycin. The novel biodegradable PHBHHxPEG appeared a promising nanocarrier for sustained delivery of hydrophobic kinase inhibitors with improved cellular uptake and kinase inhibition efficiency.
机译：背景技术蛋白激酶是细胞功能的关键调节剂，在许多人类疾病的发生和发展中起着至关重要的作用。许多激酶抑制剂已用于分子靶向治疗那些疾病，例如癌症和炎症。然而，那些高度疏水的激酶抑制剂具有生物利用度差和体内半衰期受限的共同特征，这严重阻碍了它们的实际应用。我们以前的研究表明，微生物合成的可生物降解的聚酯聚（3-羟基丁酸酯-co-3-羟基己酸酯）（PHBHHx），聚羟基链烷酸酯（PHA）家族的一员，可以用作那些疏水性激酶抑制剂的有希望的递送纳米载体。最近，通过嗜水气单胞菌发酵生产了一种新型的天然合成杂化共聚物，PEG200封端的PHBHHx（PHBHHxPEG）。在这项研究中，新型的PHBHHxPEG NPs被制备并研究用作细胞内递送纳米载体以持续释放疏水性激酶抑制剂。结果通过乳化-溶剂蒸发法制备的PHBHHxPEG纳米颗粒（NPs）为球形，直径约200？nm。雷帕霉素在PHBHHxPEG NP中的包封率为91.9％，雷帕霉素从PHBHHxPEG NP中的持续释放可以达到近10天。 PHBHHxPEG NPs的细胞摄取显着高于PHBHHx NPs。载有雷帕霉素的PHBHHxPEG NPs的抗增殖作用和mTOR抑制能力强于载有药物的PHBHHx NPs和游离雷帕霉素。结论PHBHHxPEG NPs可实现雷帕霉素的有效包封和持续释放。新型可生物降解的PHBHHxPEG似乎是一种有前途的纳米载体，可持续递送疏水性激酶抑制剂，并具有改善的细胞摄取和激酶抑制效率。

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