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用于口服给药的多交联甲基丙烯酸酯共聚物纳米颗粒的制备、建模与表征

Fabrication, modeling and characterization of multi-crosslinked methacrylate copolymeric nanoparticles for oral drug delivery.

作者信息

Ngwuluka Ndidi C, Pillay Viness, Choonara Yahya E, Modi Girish, Naidoo Dinesh, du Toit Lisa C, Kumar Pradeep, Ndesendo Valence M K, Khan Riaz A

机构信息

Department of Pharmacy and Pharmacology, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa; E-Mails:

出版信息

Int J Mol Sci. 2011;12(9):6194-225. doi: 10.3390/ijms12096194. Epub 2011 Sep 23.

Abstract

Nanotechnology remains the field to explore in the quest to enhance therapeutic efficacies of existing drugs. Fabrication of a methacrylate copolymer-lipid nanoparticulate (MCN) system was explored in this study for oral drug delivery of levodopa. The nanoparticles were fabricated employing multicrosslinking technology and characterized for particle size, zeta potential, morphology, structural modification, drug entrapment efficiency and in vitro drug release. Chemometric Computational (CC) modeling was conducted to deduce the mechanism of nanoparticle synthesis as well as to corroborate the experimental findings. The CC modeling deduced that the nanoparticles synthesis may have followed the mixed triangular formations or the mixed patterns. They were found to be hollow nanocapsules with a size ranging from 152 nm (methacrylate copolymer) to 321 nm (methacrylate copolymer blend) and a zeta potential range of 15.8-43.3 mV. The nanoparticles were directly compressible and it was found that the desired rate of drug release could be achieved by formulating the nanoparticles as a nanosuspension, and then directly compressing them into tablet matrices or incorporating the nanoparticles directly into polymer tablet matrices. However, sustained release of MCNs was achieved only when it was incorporated into a polymer matrix. The experimental results were well corroborated by the CC modeling. The developed technology may be potentially useful for the fabrication of multi-crosslinked polymer blend nanoparticles for oral drug delivery.

摘要

在提高现有药物治疗效果的探索中,纳米技术仍是有待开拓的领域。本研究探索了用于左旋多巴口服给药的甲基丙烯酸酯共聚物 - 脂质纳米颗粒(MCN)系统的制备。采用多交联技术制备纳米颗粒,并对其粒径、zeta电位、形态、结构改性、药物包封率和体外药物释放进行表征。进行了化学计量学计算(CC)建模以推导纳米颗粒合成的机制,并证实实验结果。CC建模推断纳米颗粒的合成可能遵循混合三角形结构或混合模式。发现它们是中空纳米胶囊,尺寸范围为152 nm(甲基丙烯酸酯共聚物)至321 nm(甲基丙烯酸酯共聚物共混物),zeta电位范围为15.8 - 43.3 mV。这些纳米颗粒可直接压片,并且发现通过将纳米颗粒制成纳米混悬液,然后直接压制成片剂基质或将纳米颗粒直接掺入聚合物片剂基质中,可以实现所需的药物释放速率。然而,只有当MCNs掺入聚合物基质中时才能实现持续释放。CC建模很好地证实了实验结果。所开发的技术可能对制备用于口服给药的多交联聚合物共混纳米颗粒具有潜在的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03e7/3189777/efc0bf25df47/ijms-12-06194f1.jpg

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