多种模型药物离子配合物在优化的表面活性剂和助溶剂胶束基础上的混合胶束配方:体外给药效率分析

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ahmad Saleh Malkawi, Collins Ovenseri Airemwen, Azhar Malkawi
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引用次数: 0

摘要

目的研制各种模型药物的胶束配合物,并考察其给药效果。方法选择ponceau 4R、卡托普利和荧光素作为模型药物,与三种乌龙茶基聚合物(乌龙茶RL、RS和E)形成离子配合物。形成的模型药物配合物为乌达吉特RL-ponceau 4R (RLP)、乌达吉特RS-ponceau 4R (RSP)、乌达吉特rs -卡托普利(RSC)、乌达吉特e -卡托普利(EC)和乌达吉特rs -荧光素(RSF)。RLP、RSP、RSC、EC和RSF分别加入由40% Kolliphor RH 40、20% Kolliphor EL、15% Capmul MCM和25%二丙二醇组成的胶束碱中,形成MRLP、MRSP、MRSC、MEC和MRSF胶束配合物。胶束配合物在生理缓冲介质(pH 7.4)中稀释,并对其大小、多分散性指数(PDI)、zeta电位、临界胶束浓度(CMC)和对Caco-2细胞的安全性进行表征。通过药物释放研究、细胞摄取和共聚焦显微镜研究了胶束复合物在模型药物递送中的效率。结果微束配合物保持了稳定的尺寸(14.38 ~ 91.38 nm), PDI≤0.3,zeta电位在+ 2.21 ~ + 12.23 mV范围内。所有胶束制剂的CMC在130 ~ 230µg/mL范围内。在0.5:100、1:100、2:100和3:100稀释时,胶束复合物保持了相当大的安全极限,Caco-2细胞的细胞存活率为85-100%。所有胶束配合物均具有良好的缓释作用,4 ~ 6 h内平均释放率为94.85±1.42%。胶束配合物对模型药物的释放符合一级动力学。相比之下,细胞对胶束复合物中模型药物的摄取明显高于游离模型药物溶液(p≤0.001)。MRLP和MRSP、MRSC和MEC以及MRSF分别比ponceau 4R、卡托普利和荧光素作为自由模型药物溶液高出5.7- 9.4倍、2.9- 4.4倍和4.2倍的模型药物细胞摄取。共聚焦显微成像显示了显著的荧光强度,表明荧光素从MRSF细胞摄取。结论所研究的胶束复合物具有持续的最佳药物释放和显著增强的模型药物细胞摄取,同时保持足够的生物相容性,为有效的药物递送载体提供了证据。图形抽象
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Formulation of Mixed Micelles of Various Model Drug Ionic Complexes in an Optimized Micellar Base Composed of Surfactants and Cosolvent Mixture: In Vitro Analysis of Drug Delivery Efficiency

Formulation of Mixed Micelles of Various Model Drug Ionic Complexes in an Optimized Micellar Base Composed of Surfactants and Cosolvent Mixture: In Vitro Analysis of Drug Delivery Efficiency

Objective

In this study, micellar complexes of various model drugs were developed and investigated for drug delivery efficiency.

Method

Ponceau 4R, captopril, and fluorescein were chosen as model drugs to form ionic complexes with three Eudragit-based polymers (Eudragit RL, RS, and E). The formed model drug complexes were Eudragit RL-ponceau 4R (RLP), Eudragit RS-ponceau 4R (RSP), Eudragit RS-captopril (RSC), Eudragit E-captopril (EC), and Eudragit RS-fluorescein (RSF). RLP, RSP, RSC, EC, and RSF were incorporated into a micellar base composed of 40% Kolliphor RH 40, 20% Kolliphor EL, 15% Capmul MCM, and 25% dipropylene glycol to form MRLP, MRSP, MRSC, MEC, and MRSF micellar complexes, respectively. Micellar complexes were diluted in physiological buffer media (pH 7.4) and characterized regarding the size, polydispersity index (PDI), zeta potential, critical micelle concentration (CMC), and safety on Caco-2 cells. Micellar complex efficiency in model drug delivery was investigated through a drug release study, cellular uptake, and confocal microscopy.

Results

Micellar complexes preserved a stabilized size (14.38–91.38 nm) with a PDI ≤ 0.3 and exhibited a zeta potential in the range of + 2.21 mV to + 12.23 mV. CMC of all micellar formulations was in the range of 130–230 µg/mL. At 0.5:100, 1:100, 2:100, and 3:100 dilutions, micellar complexes maintained a considerable safety limit, shown as 85–100% cell viability over Caco-2 cells. All micellar complexes were compatible for a sustained drug release with an average of 94.85 ± 1.42% model drug release within 4–6 h. The release pattern of model drugs from the micellar complexes followed First-order kinetics. Comparatively, cellular uptake of model drugs from the micellar complexes was significantly higher as compared to the control of free model drug solutions (p ≤ 0.001). MRLP and MRSP, MRSC and MEC, and MRSF showed 5.7- to 9.4-fold, 2.9- to 4.4-fold, and 4.2-fold higher model drug cellular uptake than ponceau 4R, captopril, and fluorescein as free model drug solutions, respectively. Confocal microscopic imaging showed a remarkable fluorescent intensity as an indication of fluorescein cellular uptake from MRSF.

Conclusion

The studied micellar complexes provided proof of an efficient drug delivery vehicle by showing a sustained optimum drug release and a significantly enhanced model drug cellular uptake while maintaining adequate biocompatibility.

Graphical Abstract

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来源期刊
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
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