Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

IF 0.3 Q4 PHARMACOLOGY & PHARMACY
A. Chettupalli, Purnachandra Rao Avula, Vivek Chauhan
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Abstract

The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. The optimized NLCs formulation was found to have mean vesicle sizes of 128.72±1.59 nm, polydispersity indices of 0.169±0.06, zeta potentials of -36.81±0.42 mV, and entrapment efficiencies of 79.84±0.11%. The optimized NLCs formulation released much more LCH (88.74±4.62) than the LCH-suspension (36.84±0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.
纳米结构脂质载体改善了抗高血压药物的透皮给药:统计设计、优化、描述和药代动力学评估
血管选择性钙通道阻滞剂盐酸氯卡尼平(LCH)由于溶解度低和肝脏代谢,口服吸收率很低(生物利用度仅为 10%)。由于 LCH 的溶解度和渗透性较差,因此生物利用度很低且变化很大,稳定的水性液体制剂很难制造,药物的均匀分布几乎不可能实现。 本研究的目的是探讨是否可以采用开发纳米结构脂质载体(NLCs)的方法来创造一种有效、创新的 LCH 口服制剂。研究人员采用热均质-超声策略比较了几种合成和天然液态脂质的疗效。 通过热均质化和超声波处理进行初步改进后,利用方框-贝肯统计分析对LCH负载NLCs配方进行了微调。最佳的 LCHNLCs 成分包括硬脂酸和油酸脂相(2-4% w/v)、表面活性剂 poloxamer 188(1%)和 Tween 80(1%)以及其他成分。 优化后的 NLCs 配方的平均囊泡大小为 128.72±1.59 nm,多分散指数为 0.169±0.06,zeta 电位为 -36.81±0.42 mV,夹带效率为 79.84±0.11%。在长达 24 小时的体外药物释放实验中,优化的 NLCs 制剂释放的 LCH(88.74±4.62)远高于 LCH 悬浮液(36.84±0.37%)。对 LCH-NLCs 通过肠道能力的体内外研究表明,药物渗透性比普通 LCH 溶液好得多。体内药效学分析表明,与传统的 LCH 悬浮液相比,NLCs 释放 LCH 的速度更慢,且释放时间更长。 这些研究结果进一步证明,NLCs 作为一种治疗高血压的给药技术大有可为,正如它们作为一种治疗 LCH 的控释制剂大有可为一样。
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来源期刊
Current Drug Therapy
Current Drug Therapy PHARMACOLOGY & PHARMACY-
CiteScore
1.30
自引率
0.00%
发文量
50
期刊介绍: Current Drug Therapy publishes frontier reviews of high quality on all the latest advances in drug therapy covering: new and existing drugs, therapies and medical devices. The journal is essential reading for all researchers and clinicians involved in drug therapy.
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