The influence of log P value of insoluble drugs on drug-loading properties of nano-lipid emulsion
-
摘要: 目的 考察难溶性药物油/水分配系数(log P值)对纳米脂肪乳载药量、体外释药特性、相分布等载药特性的影响。 方法 选取6种难溶性药物:尼莫地平(NIM)、多西紫杉醇(DTX)、姜黄素(CUR)、紫杉醇(PTX)、替尼泊苷(TEN)、水飞蓟宾(SLB),分别考察其log P值与PEG400中溶解度、载药纳米脂肪乳的载药量、粒径、Zeta电位、体外释药特性以及相分布等的关系。 结果 随着log P值的增加,药物在PEG400中的溶解度呈先上升后下降的趋势,在纳米脂肪乳中的载药量增高,体外释放速率减慢,在油相中的分布增加,在乳化剂层的分布减小;药物log P值与载药纳米脂肪乳的粒径及Zeta电位无关。 结论 可综合考虑药物的log P值及PEG400中的溶解度,用以初步判断纳米脂肪乳的载药特性。Abstract: Objective To study the influence on common logarithm of partition-coefficient (log P) value of insoluble drugs on nano-lipid emulsion properties, including drug-loading amount, in vitro release, and phase distribution etc. Methods 6 insoluble drugs, nimodipine (NIM), docetaxel (DTX), curcumin (CUR), paclitaxel (PTX), teniposide (TEN), silybin (SLB), were selected as the model drugs, to investigate the relationship between log P value and nano-lipid emulsion of the dissolubility in PEG400, the amount of drug-loading, particle diameter, Zeta potential, in vitro release, and phase distribution respectively. Results With the increase of log P value, drug solubility in PEG400 first increased and then decreased, drug-loading in nano-lipid emulsion increased, release rate in vitro of drug slowed down, drug distribution in oil phase increased while in emulsion layer decreased. Log P value has no correlation with particle diameter and Zeta potential. Conclusion The properties of drug-loading nano-lipid emulsion can be preliminarily judged by log P values and the solubility in PEG400 of drugs.
-
Key words:
- lipid emulsion /
- insoluble drug /
- log P value /
- drug-loading properties
-
[1] Jing X, Deng L, Gao B, et al. A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel[J]. Nanomedicine, 2014, 10(2): 371-380. [2] 张婷婷,徐 文,胡生亮,等. 水飞蓟宾在不同介质中平衡溶解度和表观分配系数的测定[J]. 中国药学杂志,20006,41(20):1569-1571. [3] Setthacheewakul S, Mahattanadul S, Phadoongsombut N, et al. Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats[J]. Eur J Pharm Biopharm, 2010, 76(3): 475-485. [4] Shaikh J, Ankola DD, Beniwal V, et al. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer[J]. Eur J Pharm Sci, 2009, 37(3-4): 223-230. [5] 高晓黎,孙殿甲,程利勇,等. 去氢骆驼蓬碱注射用乳剂中药物的相分布和体外释放研究[J].中成药,2000,22(2):111-115. [6] Korinth G, Wellner T, Schaller K. H, et al. Potential of the octanol-water partition coefficient (logP) to predict the dermal penetration behaviour of amphiphilic compounds in aqueous solutions[J]. Toxicol Lett, 2012, 215(1): 49-53. [7] 苏德森,王思玲. 物理药剂学[M]. 北京:化学工业出版社,2004:78-92. [8] Maiti K, Mukherjee K, Gantait A, et al. Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats[J]. Int J Pharm, 2007, 330(1-2): 155-163. [9] Zanotto-Filho A, Coradini K, Braganhol E, et al. Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment[J]. Eur J Pharm Biopharm, 2013, 83(2): 156-167. -
点击查看大图
计量
- 文章访问数: 3328
- HTML全文浏览量: 334
- PDF下载量: 343
- 被引次数: 0
下载:
