Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: Can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy?
Development of potent oral nanoparticulate formulation of coenzyme Q10 for treatment of hypertension: Can the simple nutritional supplements be used as first line therapeutic agents for prophylaxis/therapy?
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DOI：
10.1016/j.ejpb.2007.03.010
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发表时间：
2007-09-01
影响因子：
4.9
通讯作者：
Kumar, M. N. V. Ravi
中科院分区：
文献类型：
--
作者：
Ankola, D. D.;Viswanad, B.;Kumar, M. N. V. Ravi
辅酶Q10(CoQ10)是一种抗氧化剂，对几种慢性疾病具有良好的药理活性；然而，它只作为一种营养补充剂上市，没有任何关于其治疗活性的声明，原因之一可能是口服生物利用度较低，导致难以给药达到治疗浓度。因此，本研究旨在通过纳米制剂的形式来提高辅酶Q10的口服生物利用度。以季铵盐双十二烷基二甲基溴化铵(DMAB)为稳定剂，采用乳化法制备了聚丙交酯-乙交酯共聚物(PLGA)可生物降解纳米粒制剂。考察了初始载药量为5-75%时，辅酶Q10的包封率和包封率对包封率和包封率的影响，包封率为61-83%，载药量为5-30%(107-110 nm)时，包封率没有明显增加。然而，50%和75%的包封剂会导致包封率增加，但包封率没有明显变化。研究了辅酶Q10在市售制剂--羧甲基纤维素钠(CIRICE)和开发的纳米颗粒制剂中的混悬液在雄性SD大鼠体内的肠道摄取，结果分别为45%、75%和79%，表明纳米颗粒制剂克服了辅酶Q10的溶解性和渗透性相关的问题。此外，对开发的纳米颗粒制剂在肾性高血压动物(Goldblatt 2K1C模型)中的治疗潜力进行了评估，显示出与CoQ10混悬液相比，剂量降低60%时的疗效更好，并且比同等剂量的商业制剂更有效。综上所述，这些结果表明，纳米技术在提高辅酶Q10等分子的治疗价值方面具有潜力，有助于将其用作一线治疗剂，从而彻底改变其在当前医学治疗中的作用。(C)2007 Elsevier B.V.保留所有权利。
Coenzyme Q10 (CoQ10) is an antioxidant with well-established pharmacological activities against several chronic diseases; however, it is marketed only as a nutritional supplement without any claims of its therapeutic activity and one of the reasons for this could be the poor oral bioavailability rendering difficulties in administering this molecule to achieve therapeutic concentrations. Therefore, the present investigation was aimed at improving the oral bioavailability of CoQ10 by delivering it as nanoparticulate formulation. Biodegradable nanoparticulate formulations based on poly(lactide-co-gylcolide) (PLGA) were prepared by emulsion technique using quaternary ammonium salt didodecyldimethylammonium bromide (DMAB) as a stabilizer. The effect of initial CoQ10 loading on entrapment efficiency and the particle size was studied using 5-75% initial load resulting in good entrapment efficiency (61-83%) without any appreciable increase in the particle size for 5-30% loading (107-110 nm). However, 50% and 75% led to increase in particle size with no appreciable changes in entrapment efficiency. The intestinal uptake of CoQ10 as a suspension in carboxymethylcellulose (CIVIC), a commercial formulation and the developed nanoparticulate formulation was studied in male Sprague-Dawley (SD) rats and found to be 45%, 75% and 79%, respectively, suggesting that solubility and permeability related problems of CoQ10 were overcome by nanoparticulate formulation. Furthermore, the developed nanoparticulate formulation was evaluated for its therapeutic potential in renal hypertensive animals (Goldblatt 2K1C model), demonstrating improved efficacy at a 60% lowered dose as compared to CoQ10 suspension and superior efficacy than the commercial formulation at an equal dose. Together, these results indicate the potential of nanotechnology in improving the therapeutic value of molecules like CoQ10, facilitating its usage as first line therapeutic agent thus revolutionizing its role in current medical therapy. (c) 2007 Elsevier B.V. All rights reserved.