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超分子化学能够实现新型水溶性片剂的 vat 光聚合 3D 打印。

Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets.

机构信息

Department of Pharmaceutics, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.

School of Chemistry and Biosciences, University of Bradford, Richmond Road, BD7 1DP, UK.

出版信息

Int J Pharm. 2023 Aug 25;643:123286. doi: 10.1016/j.ijpharm.2023.123286. Epub 2023 Jul 31.

DOI:10.1016/j.ijpharm.2023.123286
PMID:37532009
Abstract

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines.

摘要

立体光固化技术因其能够制造个性化药物而受到药物研究人员的关注,尤其适用于需要高精度剂量或对热不稳定的药物。然而,迄今为止,所制造的 3D 打印结构都是不可溶的,这限制了可打印剂型为持续释放系统或药物洗脱医疗器械,因为这些剂型不需要溶解打印基质。能够产生水溶性结构的树脂将能够实现更具多样性的药物释放特性,并扩大潜在应用。为了实现这一目标,不是采用交联化学来制造基质,而是可以使用超分子化学在聚合物链之间赋予动态相互作用。在这项研究中,首次通过数字光处理(DLP)3DP 制造水溶性载药打印体(3D 打印片剂)。制备了六种具有不同比例电解质丙烯酰胺单体[2-(丙烯酰氧基)乙基]三甲基氯化铵(TMAEA)和共聚单体 1-乙烯基-2-吡咯烷酮(NVP)的配方,以制造对乙酰氨基酚载药打印体。1 H NMR 光谱分析证实了 TMAEA 和 NVP 整合在聚合物中,并且仅痕量存在残留的 TMAEA 单体(0.71-1.37%w/w)。根据 H DOSY NMR 测量,光聚合聚合物的表观分子量超过 300,000 Da,水动力半径为 15-20nm。负载的对乙酰氨基酚在 45 分钟至 5 小时之间完全从打印体中释放出来。在大鼠体内单次急性毒性研究中,表明打印体不会引起任何组织损伤。本研究报告的结果代表了朝着采用基于立体光固化技术的 3DP 制造个性化药物迈出的重要一步。

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