Jain Subheet, Tiwary A K, Jain N K
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour, University, SAGAR, 470 003, India.
Curr Drug Deliv. 2006 Apr;3(2):157-66. doi: 10.2174/156720106776359221.
The present study is aimed at evaluating the transdermal route as an alternative to the oral route for improving the systemic bioavailability and sustaining the constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal formulations of AZT were prepared and characterized. The effect of different formulation variables on transdermal delivery of AZT from elastic liposomes was studied. To investigate the mechanism of skin permeation of elastic liposomes, Transmission Electron Microscopic (TEM) study was carried out. The optimized elastic liposomal formulation showed transdermal flux of 98.8+/-5.8 microg/cm2/hr across rat skin as compared to 5.72+/-0.3 microg/cm2/hr for free drug. Vesicle-skin interaction study showed that elastic vesicles influenced the ultra structure of stratum corneum. Distinct regions with lamellar stacks derived from vesicles were observed in intercellular spaces of the stratum corneum. These stacks disrupted the organization of skin bilayers leading to increased skin permeability, whereas no changes were observed in the underlying viable epidermis and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to be (12.63+/-1.2 microg h/mL), nearly twelve fold higher than the control (0.83+/-0.2 microg h/mL). Furthermore, the administration of elastic liposome encapsulated AZT resulted in substantially higher accumulation of AZT in target RES organs that play a key role in the pathogenesis of AIDS by providing long-term reservoir for the virus. The results of the present study demonstrated that elastic liposomes increased the transdermal flux, prolonged the release, improved the site specificity of AZT and represented an attractive strategy for sustained and targeted delivery of AZT.
本研究旨在评估经皮给药途径作为口服给药途径的替代方法，以提高齐多夫定（AZT）的全身生物利用度并维持其恒定的治疗血浆水平。制备并表征了AZT的弹性脂质体制剂。研究了不同制剂变量对AZT从弹性脂质体经皮递送的影响。为了研究弹性脂质体的皮肤渗透机制，进行了透射电子显微镜（TEM）研究。优化后的弹性脂质体制剂在大鼠皮肤上的经皮通量为98.8±5.8μg/cm²/小时，而游离药物的经皮通量为5.72±0.3μg/cm²/小时。囊泡-皮肤相互作用研究表明，弹性囊泡影响角质层的超微结构。在角质层的细胞间空间中观察到来自囊泡的具有层状堆积的不同区域。这些堆积破坏了皮肤双层的组织结构，导致皮肤通透性增加，而在下面的活表皮和真皮中未观察到变化。当AZT包封在弹性脂质体中时，观察到药代动力学特征得到改善。弹性脂质体制剂的AUC0-24h为（12.63±1.2μg h/mL），比对照（0.83±0.2μg h/mL）高近12倍。此外，给予弹性脂质体包裹的AZT导致AZT在靶RES器官中的蓄积显著增加，这些器官通过为病毒提供长期储存库在艾滋病发病机制中起关键作用。本研究结果表明，弹性脂质体增加了经皮通量，延长了释放时间，提高了AZT的位点特异性，是一种有吸引力的AZT持续和靶向递送策略。
