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无针喷射注射器与纳米混悬液:探索一对意外组合的潜力。

Needle-Free Jet Injectors and Nanosuspensions: Exploring the Potential of an Unexpected Pair.

作者信息

Schlich Michele, Casula Luca, Musa Aurora, Pireddu Rosa, Pitzanti Giulia, Cardia Maria Cristina, Valenti Donatella, Marceddu Salvatore, Fadda Anna Maria, De Luca Maria Antonietta, Sinico Chiara, Lai Francesco

机构信息

Dipartimento di Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, CNBS, Università degli Studi di Cagliari, 09124 Cagliari, Italy.

Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy.

出版信息

Pharmaceutics. 2022 May 19;14(5):1085. doi: 10.3390/pharmaceutics14051085.

Abstract

Needle-free liquid jet injectors are medical devices used to administer pharmaceutical solutions through the skin. Jet injectors generate a high-speed stream of liquid medication that can puncture the skin and deliver the drug to the underlying tissues. In this work, we investigated the feasibility of using liquid jet injectors to administer nanosuspensions, assessing the impact of the jet injection on their pharmaceutical and physicochemical properties. For this purpose, the model drug diclofenac was used to prepare a set of nanosuspensions, stabilized by poloxamer 188, and equilibrated at different pHs. The hydrodynamic diameter and morphology of the nanocrystals were analyzed before and after the jet injection across porcine skin in vitro, together with the solubility and release kinetics of diclofenac in a simulated subcutaneous environment. The efficacy of the jet injection (i.e., the amount of drug delivered across the skin) was evaluated for the nanosuspension and for a solution, which was used as a control. Finally, the nanosuspension was administered to rats by jet injector, and the plasma profile of diclofenac was evaluated and compared to the one obtained by jet injecting a solution with an equal concentration. The nanosuspension features were maintained after the jet injection in vitro, suggesting that no structural changes occur upon high-speed impact with the skin. Accordingly, in vivo studies demonstrated the feasibility of jet injecting a nanosuspension, reaching relevant plasma concentration of the drug. Overall, needle-free jet injectors proved to be a suitable alternative to conventional syringes for the administration of nanosuspensions.

摘要

无针液体喷射注射器是用于通过皮肤给药的医疗设备。喷射注射器产生高速液体药物流,该药物流可穿透皮肤并将药物输送到下层组织。在这项工作中,我们研究了使用液体喷射注射器给药纳米混悬液的可行性,评估了喷射注射对其药物和物理化学性质的影响。为此,使用模型药物双氯芬酸制备了一组纳米混悬液,用泊洛沙姆188稳定,并在不同pH值下平衡。在体外通过猪皮肤进行喷射注射前后,分析了纳米晶体的流体动力学直径和形态,以及双氯芬酸在模拟皮下环境中的溶解度和释放动力学。评估了纳米混悬液和用作对照的溶液的喷射注射效果(即穿过皮肤递送的药物量)。最后,通过喷射注射器将纳米混悬液给予大鼠,并评估双氯芬酸的血浆曲线,并与通过喷射注射等浓度溶液获得的曲线进行比较。喷射注射后,纳米混悬液的特征在体外得以保持,这表明在与皮肤高速撞击时不会发生结构变化。因此,体内研究证明了喷射注射纳米混悬液的可行性,达到了药物的相关血浆浓度。总体而言,无针喷射注射器被证明是用于给药纳米混悬液的传统注射器的合适替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6c9/9144479/1fd6116b3b9d/pharmaceutics-14-01085-g001.jpg

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