Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY Current drug delivery Pub Date : 2023-01-01 DOI:10.2174/1567201819666220817111054

Arshad Ali Khan, Safia Akhtar, Yogesh Yadav, Atiya Akhtar, Walla Alelwani, Azzah M Bannunah, Syed Mahmood

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引用次数: 3

Abstract

Background: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.

Methods: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.

Results: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).

Conclusion: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.

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用于增强溶解度的洛匹那韦负载自纳米乳化药物递送系统:开发，表征和Caco-2细胞摄取。

背景:抗逆转录病毒蛋白酶抑制剂药物洛匹那韦(LPV)用于治疗HIV-1感染。已知LPV具有有限的口服生物利用度，这可能是由于其水溶性差，疗效低和首过代谢高。为了解决当前的问题，LPV的自纳米乳化给药系统(SNEDDS)已经被开发和优化。方法:采用滴定法制备LPV-SNEDDS (LPV-SNEDDS)。构建了六种不同的伪三元相图来识别纳米乳化区域。研制的配方以粒径< 100 nm、分散度≤0.5、分散性(A级)、透光率> 85为标准。通过加热-冷却循环、冻融循环和离心实验来证实所制备的SNEDDS的稳定性。结果:LPV-SNEDDS (L-14)的最终液滴尺寸为58.18±0.62 nm，多分散指数为0.326±0.005,zeta电位为-22.08±1.2 mV，包封效率(EE%)为98.93±1.18%。根据高分辨率透射电镜(HRTEM)分析，优化配方中的液滴尺寸< 60 nm。所选SNEDDS在30 min内释放了近99%的LPV，显著(p < 0.05)高于甲基纤维素中的LPV悬浮液(0.5% w/v)。这表明SNEDDS有可能提高LPV的溶解度，最终有助于提高LPV的口服生物利用度。cco -2细胞摄取研究显示，sneed (LPV- snedds - l -14)对LPV的摄取显著(p < 0.05)高于游离LPV (LPV-悬液)。结论:LPV- snedds可能是LPV口服给药的潜在载体。

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来源期刊

Current drug delivery PHARMACOLOGY & PHARMACY-

CiteScore

5.10

自引率

4.20%

发文量

170

期刊介绍： Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves. The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance. The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.