Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, UP, India.
J Biomed Nanotechnol. 2013 May;9(5):891-900. doi: 10.1166/jbn.2013.1580.
Osteoarthritis is the most common, multi component joint disease mainly characterized by destruction of articular cartilage which leads up to subchondral bone. Current treatment by NSAID's gives only symptomatic relief but semi-synthetic anthraquinone diacerein is novel chondroprotective agent intended for the treatment of osteoarthritis. Its active metabolite rhein inhibits the agents responsible for cartilage degradation. In the present study, stearic acid, long chain fatty acids, based solid lipid nanoparticles were prepared with enhanced oral bioavailability and lesser side effects. Diacerein loaded solid lipid nanoparticles were prepared by modified high shear homogenization with ultrasonication method using stearic acid as lipid. Pluronic F68 and soya lecithin was used as surfactant. Citric acid was added to give acidic environment to drug. Solid lipid nanoparticles were evaluated for different characterization parameters, in-vitro performance and in-vivo pharmacokinetics and anti-diarrhoeal study. Particle size of the diacerein loaded SLN was found in the range of 270 +/- 2.1 to 510 +/- 2.8 nm with zeta potential -13.78 +/- 3.4 mV to -19.66 +/- 2.1 mV. Maximum entrapment efficiency was achieved up to 88.1 +/- 1.3%. Surface and solid state characterization by TEM, XRD and DSC revealed that all particles are spherical in shape and drug entrapped inside lipid was in amorphous state. In-vitro release was done by dialysis bag method in phosphate buffer (pH 5.8) which showed controlled and extended release profile up to 12 hr. In-vivo pharmacokinetic study reveals an increase in Area Under Curve from 26.68 +/- 1.63 to 71.25 +/- 1.25 hr microg ml(-1). Further diarrhoeal side effect of diacerein was also found to reduce up to 37% by lipid nanoparticles. These results suggest that diacerein loaded solid lipid nanoparticles can be prepared efficiently with stearic acid and produces controlled and prolonged drug release profile. The oral bioavailability was enhanced by around 2.7 times and with lesser diarrhoeal side effects. These all will leads to overall improvement in patient compliance for the treatment.
骨关节炎是最常见的多成分关节疾病，主要特征为关节软骨破坏，进而导致软骨下骨。目前的非甾体抗炎药治疗只能缓解症状，但半合成蒽醌二乙酰半胱氨酸是一种新型的软骨保护剂，用于治疗骨关节炎。其活性代谢产物大黄酸可抑制导致软骨降解的物质。在本研究中，我们制备了基于硬脂酸的长链脂肪酸固体脂质纳米粒，以提高口服生物利用度，减少副作用。采用改良的高剪切匀化法，以硬脂酸为脂质，超声法制备二乙酰半胱氨酸固体脂质纳米粒。使用泊洛沙姆 F68 和大豆卵磷脂作为表面活性剂。添加柠檬酸使药物处于酸性环境中。对固体脂质纳米粒进行了不同的特性参数、体外性能和体内药代动力学以及抗腹泻研究。二乙酰半胱氨酸载药 SLN 的粒径为 270±2.1 至 510±2.8nm，zeta 电位为-13.78±3.4mV 至-19.66±2.1mV。最大包封效率达到 88.1±1.3%。通过 TEM、XRD 和 DSC 进行表面和固态特性研究表明，所有颗粒均为球形，药物包埋于脂质中呈无定形态。采用透析袋法在磷酸盐缓冲液（pH5.8）中进行体外释放，结果表明，药物可在 12 小时内得到控制和延长释放。体内药代动力学研究表明，AUC 从 26.68±1.63 增加到 71.25±1.25hrμgml(-1)。进一步的研究发现，二乙酰半胱氨酸的腹泻副作用也减少了 37%。这些结果表明，用硬脂酸可以有效地制备二乙酰半胱氨酸载药固体脂质纳米粒，产生控制和延长药物释放的特性。口服生物利用度提高了约 2.7 倍，腹泻副作用减少。这些都将使患者的治疗依从性得到整体改善。
