TPGS conjugated pro-liposomal nano-drug delivery system potentiate the antioxidant and hepatoprotective activity of Myricetin

Myricetin (MRC) is a naturally occurring herbal flavonoid compound that has been recognized as a useful medicinal agent over a long time, but its applications have been restricted due to its poor aqueous solubility, stability, and bioavailability. This study was designed to promote the bioavailability and therapeutic efficacy of MRC via the two novel pro-liposomes formulations, one with and one without Vitamin E TPGS (d-α-tocopherol polyethylene glycol 1000 Succinate) using thin-film method, denoted as MRC-PL and MRC-TPGS-PL. Successfully formulated nano pro-liposomes were spherical in shape, uniformly distributed and possessed in vitro controlled release profile. The small particle size (<50 nm), high encapsulation efficiency (>94%) and drug loading capacity (>6.5%) indicated a strong affinity between MRC and the core of the nano pro-liposomes. An in vivo pharmacokinetic study showed that the oral bioavailability of MRC increased by 7.2-fold when loaded into TPGS modified pro-liposome thus leading to enhanced therapeutic efficacy. Therefore, significantly better pharmacological effects, especially antioxidant and hepatoprotective activity of MRC, were achieved via TPGS modified pro-liposome formulation rather than the TPGS-free pro-liposome and unformulated MRC. Based on these findings, it was hypothesized that TPGS modified pro-liposomes could be potential nanocarriers for overcoming the limitations in delivery of hydrophobic compounds via the oral route.