Institute for Drug Delivery and Biomedical Research, Bangalore, India.
Curr Drug Deliv. 2021;18(4):421-432. doi: 10.2174/1567201817666201014144708.
Topical therapy is ineffective in the case of Musculoskeletal Disorders (MSD) as it is not able to maintain therapeutic levels of the drug in the affected joint due to its inability to surpass the dermal circulation and penetrate into deeper tissues. One of the approaches to enhance deep tissue penetration of drugs is to increase drug delivery much above the dermal clearance. The objective of the present work was to formulate negatively charged Deformable Liposomes (DL) of Diclofenac Sodium (DS) using biosurfactants and target the same to the synovial fluid by application of iontophoresis.
Deformable liposomes loaded with diclofenac sodium were formulated and characterized for surface morphology, particle size distribution, zeta potential and entrapment efficiency. In vitro permeation of the diclofenac from aqueous solution, conventional liposomes, and deformable liposomes under iontophoresis was performed using Franz diffusion cells and compared to passive control. Intraarticular microdialysis was carried out to determine the time course of drug concentration in the synovial fluid at the knee-joint region of the hind limb in Sprague Dawley rats.
The vesicles were found to display a high entrapment (> 60%) and possess a negative zeta potential lower than -30 mV. The size of the vesicles was varied from 112.41 ± 1.42 nm and 154.6 ± 3.22 nm, demonstrated good stability on the application of iontophoresis. The iontophoretic flux values for the DS aqueous solution, conventional liposomes and deformable liposomal formulation were found to be 7.55 ± 0.42, 16.75±1.77and 44.01 ± 3.47 μg/ cm h, respectively. Deformable liposomes were found to display an enhancement of 5.83 fold compared to passive control. Iontophoresis was found to enhance the availability of DS deformable liposomes (0.56 ± 0.08 μg.h/ml) in the synovial fluid by nearly 2-fold over passive delivery (0.29 ± 0.05 μg.h/ml).
Results obtained indicate that iontophoretic mediated transport of deformable liposomes could improve the regional bioavailability of diclofenac sodium to the synovial joints, an efficient mode for treating MSD in the elderly.
局部治疗在肌肉骨骼疾病（MSD）中效果不佳，因为它无法超越皮肤循环并渗透到更深的组织中，因此无法维持药物在受影响关节中的治疗水平。增加药物向深层组织的渗透的方法之一是将药物输送量提高到超过皮肤清除率以上。本工作的目的是使用生物表面活性剂制备并表征载双氯芬酸钠的负变形脂质体（DL），并通过电渗将其靶向到滑液。
制备并表征载双氯芬酸钠的变形脂质体，以评估其表面形态、粒径分布、Zeta 电位和包封效率。通过 Franz 扩散池，对双氯芬酸钠从水溶液、普通脂质体和电渗条件下的变形脂质体中的体外渗透进行了研究，并与被动对照进行了比较。在 Sprague Dawley 大鼠后肢膝关节部位进行关节内微透析，以确定滑液中药物浓度的时间过程。
发现囊泡的包封率>60%，Zeta 电位低于-30 mV。囊泡的粒径为 112.41±1.42nm 和 154.6±3.22nm，在施加电渗时显示出良好的稳定性。双氯芬酸钠水溶液、普通脂质体和变形脂质体制剂的电渗通量值分别为 7.55±0.42、16.75±1.77 和 44.01±3.47μg/cm h。与被动对照相比，变形脂质体显示出 5.83 倍的增强作用。电渗作用使双氯芬酸钠变形脂质体（0.56±0.08μg.h/ml）在滑液中的可用性提高了近 2 倍（0.29±0.05μg.h/ml）。
结果表明，变形脂质体的电渗介导输送可以提高双氯芬酸钠在滑膜关节中的区域生物利用度，这是治疗老年人 MSD 的一种有效方式。
