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基于聚己内酯的 3D 打印可生物降解植入物涂层:一种延长亲水性药物释放的新策略。

Poly(caprolactone)-Based Coatings on 3D-Printed Biodegradable Implants: A Novel Strategy to Prolong Delivery of Hydrophilic Drugs.

机构信息

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, U.K.

Instituto De Cerámica y Vidrio, CSIC, c/Kelsen, 5, 28049 Madrid, Spain.

出版信息

Mol Pharm. 2020 Sep 8;17(9):3487-3500. doi: 10.1021/acs.molpharmaceut.0c00515. Epub 2020 Aug 3.

Abstract

Implantable devices are versatile and promising drug delivery systems, and their advantages are well established. Of these advantages, long-acting drug delivery is perhaps the most valuable. Hydrophilic compounds are particularly difficult to deliver for prolonged times. This work investigates the use of poly(caprolactone) (PCL)-based implant coatings as a novel strategy to prolong the delivery of hydrophilic compounds from implantable devices that have been prepared by additive manufacturing (AM). Hollow implants were prepared from poly(lactic acid) (PLA) and poly(vinyl alcohol) (PVA) using fused filament fabrication (FFF) AM and subsequently coated in a PCL-based coating. Coatings were prepared by solution-casting mixtures of differing molecular weights of PCL and poly(ethylene glycol) (PEG). Increasing the proportion of low-molecular-weight PCL up to 60% in the formulations decreased the crystallinity by over 20%, melting temperature by over 4 °C, and water contact angle by over 40°, resulting in an increased degradation rate when compared to pure high-molecular-weight PCL. Addition of 30% PEG to the formulation increased the porosity of the formulation by over 50% when compared to an equivalent PCL-only formulation. These implants demonstrated release rates for hydrophilic model compounds (methylene blue and ibuprofen sodium) ranging from 0.01 to 34.09 mg/day, depending on the drug used. The versatility of the devices produced in this work and the range of release rates achievable show great potential. Implants could be specifically developed in order to match the specific release rate required for a number of drugs for a wide range of conditions.

摘要

可植入装置是多功能且有前途的药物输送系统,其优点已得到充分证实。在这些优点中,长效药物输送也许是最有价值的。亲水化合物尤其难以长时间输送。这项工作研究了使用基于聚己内酯(PCL)的植入涂层作为一种新策略,从通过增材制造(AM)制备的可植入装置中延长亲水化合物的输送。使用熔融灯丝制造(FFF)AM 从聚乳酸(PLA)和聚乙烯醇(PVA)制备空心植入物,然后用基于 PCL 的涂层进行涂层。通过溶液浇铸不同分子量的 PCL 和聚乙二醇(PEG)的混合物制备涂层。与纯高分子量 PCL 相比,配方中低分子量 PCL 的比例增加到 60%,结晶度降低了 20%以上,熔融温度降低了 4°C 以上,水接触角增加了 40°以上,导致降解速度增加。与等效的仅 PCL 配方相比,在配方中添加 30%PEG 可使配方的孔隙率增加 50%以上。这些植入物对亲水模型化合物(亚甲蓝和布洛芬钠)的释放速率在 0.01 至 34.09 mg/天之间变化,具体取决于所用药物。本工作中制备的装置的多功能性和可实现的释放速率范围显示出巨大的潜力。可以专门开发植入物,以匹配许多药物在广泛条件下所需的特定释放速率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b53/7482401/0a0d959ef0a3/mp0c00515_0001.jpg

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