Bisdemethoxycurcumin-conjugated vitamin E TPGS liposomes ameliorate poor bioavailability of free form and evaluation of its analgesic and hypouricemic activity in oxonate-treated rats

摘要

Recently, bisdemethoxycurcumin (BDMC), a constituent of turmeric, has been studied widely in view of their various therapeutic effects, namely anti-oxidant, anti-cancer, anti-diabetic, and anti-inflammatory. Since ancient times, turmeric has been extensively used as a naturally occurring traditional Chinese medicine (TCM) and as a crucial home remedy for treatment of many health problems such as inflammation and pain. However, the action of anti-gouty arthritis and analgesic activity of its constituents, especially BDMC, have not been scientifically reported yet. Despite the various bioactivities of BDMC, its utilization in clinics has been restricted owing to poor solubility and bioavailability. This research aimed at enhancing oral bioavailability and pharmacokinetic of BDMC via liposome formulation which was modified with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS or vitamin E TPGS) and was characterized using various parameters both in vitro and in vivo. Also, the analgesic and anti-gouty activities of BDMC-loaded TPGS-modified liposomes were investigated by assessing pain threshold and serum uric acid level in potassium oxonate-induced hyperuricemic rats. As the result, BDMC-loaded TPGS-modified liposomes were formulated successfully with optimal physiochemical properties such as 75.98 +/- 5.46 nm (particle size), 0.246 +/- 0.011 (polydispersity index), - 38.21 +/- 0.29 mV (zeta potential), 96.98 +/- 0.17 (encapsulation efficiency (EE)), and 4.84 +/- 0.0089 (drug loading capacity (DL)). Moreover, the oral bioavailability of liposomized BDMC was approximately 10-fold greater than free BDMC in vivo and in vitro cumulative release rates in pH 1.2 (78) and pH 7 (68) respectively. This significantly improved the sustaining drug effect of BDMC compared with free form. In addition, BDMC-TPGS liposome acted as a xanthine oxidase inhibitor to evidently reduce uric acid level in potassium oxonate-induced hyperuricemic rats and remarkably increase pain threshold capacity and reaction time in hot plate test at a dose-dependent manner. Altogether, BDMC-conjugated TPGS liposome could act as favorable nanocarriers against gouty arthritis and intense pain with prospect of overcoming the limitation of BDMC application.