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姜黄素纳米粒子作为一种多用途添加剂,可实现高保真度的 SLA-3D 打印和控制释放。

Curcumin nanoparticles as a multipurpose additive to achieve high-fidelity SLA-3D printing and controlled delivery.

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari, Assam, India; National Centre for Pharmacoengineering, NIPER-Guwahati, Changsari, Assam, India.

Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari, Assam, India.

出版信息

Biomater Adv. 2023 Oct;153:213527. doi: 10.1016/j.bioadv.2023.213527. Epub 2023 Jun 23.

Abstract

Light-based three-dimensional (3D) printing has been under use extensively to fabricate complex geometrical constructs which find a vast application in the fields of drug delivery and tissue engineering fields due to its ability to recapitulate the intricate biological architecture and thus provides avenues to achieve previously unachievable biomedical devices. The inherent problem associated with light-based 3D printing (from a biomedical perspective) is that of light scattering causing inaccurate and defective prints which results in erroneous drug loading in 3D printed dosage forms and can also render the environment of the polymers toxic for the biological cells and tissues. In this regard, an innovative additive comprising of a nature-derived drug-cum-photoabsorber (curcumin) entrapped in naturally derived protein (bovine serum albumin) is envisaged to act as a photoabsorbing system that can improve the printing quality of 3D printed drug delivery formulations (macroporous pills) as well as provide stimuli-responsive release of the same upon oral ingestion. The delivery system was designed to endure the chemically and mechanically hostile gastric environment and deliver the drug in the small intestine to improve absorption. A 3 × 3 grid macroporous pill was designed (specifically to withstand the mechanically hostile gastric environment) and 3D printed using Stereolithography comprising of a resin system including acrylic Acid, PEGDA and PEG 400 along with curcumin loaded BSA nanoparticles (Cu-BSA NPs) as a multifunctional additive and TPO as the photoinitiator. The 3D printed macroporous pills were found to show excellent fidelity to CAD design as evident from the resolution studies. The mechanical performance of the macroporous pills was found to be extremely superior to monolithic pills. The pills found to release curcumin in pH responsive manner with slower release at acidic pH but faster release at intestinal pH due to its similar swelling behavior. Finally, the pills were found to be cytocompatible to mammalian kidney and colon cell lines.

摘要

基于光的三维(3D)打印技术已广泛应用于制造复杂的几何结构,由于其能够再现复杂的生物结构,因此在药物输送和组织工程领域有广泛的应用,为实现以前无法实现的生物医学设备提供了途径。从生物医学的角度来看,基于光的 3D 打印存在固有问题,即光散射导致打印不准确和有缺陷,从而导致 3D 打印剂型中药物装载错误,并且还会使聚合物的环境对生物细胞和组织产生毒性。在这方面,设想了一种由天然衍生药物-光吸收剂(姜黄素)包封在天然衍生蛋白质(牛血清白蛋白)中的创新添加剂,作为光吸收系统,可以改善 3D 打印药物输送制剂(大孔丸)的打印质量,并提供相同的刺激响应释放。该输送系统旨在耐受化学和机械恶劣的胃环境,并将药物递送到小肠以改善吸收。设计了 3×3 网格大孔丸(专门用于承受机械恶劣的胃环境),并使用立体光刻技术进行 3D 打印,该技术由包括丙烯酸、PEGDA 和 PEG 400 的树脂系统以及负载有姜黄素的 BSA 纳米颗粒(Cu-BSA NPs)作为多功能添加剂和 TPO 作为光引发剂组成。从分辨率研究中可以明显看出,3D 打印的大孔丸与 CAD 设计具有出色的一致性。大孔丸的机械性能比整体丸更优越。发现丸在 pH 响应的情况下释放姜黄素,在酸性 pH 下释放速度较慢,但在肠道 pH 下释放速度较快,因为其具有相似的溶胀行为。最后,发现丸对哺乳动物肾和结肠细胞系具有细胞相容性。

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