Formulation of Lipid-Based Nanocarriers of Lacidipine for Improvement of Oral Delivery: Box-Behnken Design Optimization, In Vitro, Ex Vivo, and Preclinical Assessment.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Assay and drug development technologies Pub Date : 2022-01-01 Epub Date: 2021-12-31 DOI:10.1089/adt.2021.084

Dheeraj Kataria, Ameeduzzafar Zafar, Javed Ali, Karishma Khatoon, Saba Khan, Syed Sarim Imam, Mohd Yasir, Asgar Ali

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引用次数: 7

Abstract

The present research work was aimed to develop and optimize the nanostructured lipid carrier (NLCs) of the antihypertensive drug lacidipine (LAC) for the improvement of oral bioavailability and antihypertensive activity. LAC-NLCs were successfully developed by the preemulsion probe sonication technique. The formulations were optimized by Box-Behnken design and assessed for particle size (PS), polydispersity index (PDI), entrapment efficiency (EE), drug loading (DL), drug release, ex vivo permeation, and in vivo study. The optimized LAC-NLCs showed nanometric PS (191.0 ± 5.89 nm), high EE (90% ± 3.69%) and DL (9.26% ± 1.89%), negative zeta potential (-28.9 ± 0.99 mV), and narrow size distribution (PDI of 0.074 ± 0.013) with spherical morphology. The drug release study revealed that a significantly (p < 0.05) higher LAC release (88.49% ± 3.01%) was achieved from the optimized LAC-NLCs compared to LAC-dispersion (34.27% ± 3.01%). Moreover, the optimized LAC-NLCs showed significantly (p < 0.05) higher intestinal permeation (692.04 ± 19.76 μg) than LAC-dispersion (23.83 ± 5.08 μg). After oral administration of a single dose of LAC, the optimized LAC-NLCs exhibited 3.45-fold higher relative oral bioavailability as well as a more prominent antihypertensive effect than LAC-dispersion. This might be due to the high penetration and absorption of the drug. Hence, NLCs might provide an efficient nano delivery for the management of hypertension and promising drug delivery systems for the bioavailability enhancement of LAC.

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改善口服给药的脂基拉西地平纳米载体的配方:Box-Behnken设计优化、体外、离体和临床前评估。

本研究旨在开发和优化抗高血压药物拉西地平(lacidipine, LAC)的纳米结构脂质载体(NLCs)，以提高其口服生物利用度和抗高血压活性。利用乳前探针超声技术成功研制了LAC-NLCs。采用Box-Behnken设计优化处方，并对其粒径(PS)、多分散指数(PDI)、包封效率(EE)、载药量(DL)、药物释放、体外渗透和体内研究进行评价。优化后的LAC-NLCs具有纳米PS(191.0±5.89 nm)，高EE(90%±3.69%)和DL(9.26%±1.89%)，负zeta电位(-28.9±0.99 mV)，尺寸分布窄(PDI为0.074±0.013)，呈球形。药物释放研究表明，优化后的LAC- nlcs的LAC释放度(88.49%±3.01%)显著高于LAC分散度(34.27%±3.01%)(p < 0.05)。优化后的LAC-NLCs肠通透度(692.04±19.76 μg)显著高于lac -分散度(23.83±5.08 μg) (p < 0.05)。单剂量口服LAC后，优化后的LAC- nlcs的相对口服生物利用度比LAC-分散体高3.45倍，降压效果也比LAC-分散体更显著。这可能是由于药物的高渗透性和吸收率。因此，NLCs可能为高血压治疗提供有效的纳米递送，并为提高LAC的生物利用度提供有前途的药物递送系统。

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

Assay and drug development technologies 医学-生化研究方法

CiteScore

3.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application. ASSAY and Drug Development Technologies coverage includes: -Assay design, target development, and high-throughput technologies- Hit to Lead optimization and medicinal chemistry through preclinical candidate selection- Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis- Approaches to assays configured for gene families, inherited, and infectious diseases- Assays and strategies for adapting model organisms to drug discovery- The use of stem cells as models of disease- Translation of phenotypic outputs to target identification- Exploration and mechanistic studies of the technical basis for assay and screening artifacts