Fluorinated PAMAM-Arginine Carrier Prodrugs for pH-Sensitive Sustained Ibuprofen Delivery.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-08-01 Epub Date: 2024-07-24 DOI:10.1007/s11095-024-03747-6

Carola Romani, Mattia Sponchioni, Alessandro Volonterio

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引用次数: 0

Abstract

Objective: The development of an efficient, multifunctional drug delivery system overcoming different obstacles generally associated with drug formulations, including the poor accumulation of the active principle in the target site and its sustained release for prolonged time.

Methods: Our study proposes the development of a fluorinated poly(amidoamine) (PAMAM) carrier prodrug combining drug release boosted in alkaline environments with a possible implementation in ¹⁹F MRI applications. In particular, we functionalized the terminal primary amines of PAMAM G2 and G4 through an ad hoc designed fluorinated ibuprofen-arginine Michael acceptor to obtain multifunctional ibuprofen-PAMAM-Arg conjugates.

Results: These carriers demonstrated pH-dependent and sustained ibuprofen release for more than 5 days. This advantage was observed in both weak alkaline and physiological buffer solutions, allowing to overcome the limits associated to the burst release from similar fluorinated Arg-PAMAM dendrimers with ibuprofen physically encapsulated.

Conclusion: These findings, coupled to the high biocompatibility of the system, suggest a potential synergistic biomedical application of our conjugates, serving as vehicles for drug delivery and as ¹⁹F magnetic resonance imaging contrast agents.

Abstract Image

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氟化 PAMAM-精氨酸载体原药用于 pH 值敏感的布洛芬持续给药。

目的开发一种高效、多功能的给药系统，克服药物制剂通常存在的各种障碍，包括活性成分在靶点的蓄积性差和长时间的持续释放：我们的研究提出开发一种含氟聚（氨基胺）（PAMAM）载体原药，它能在碱性环境中促进药物释放，并有可能应用于 19F MRI。特别是，我们通过特别设计的氟化布洛芬-精氨酸迈克尔受体对 PAMAM G2 和 G4 的末端伯胺进行了官能化，从而获得了多功能布洛芬-PAMAM-Arg 共轭物：这些载体显示了布洛芬在 5 天以上的 pH 依赖性和持续释放。在弱碱性溶液和生理缓冲溶液中都能观察到这一优势，从而克服了类似的氟化 Arg-PAMAM 树枝状聚合物在布洛芬物理包封后的猝灭释放限制：这些发现以及该系统的高生物相容性表明，我们的共轭物具有潜在的协同生物医学应用前景，既可作为药物输送载体，也可作为 19F 磁共振成像对比剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.