Preparation, optimization, and pharmacokinetic study of nanoliposomes loaded with triacylglycerol‐bound punicic acid for increased antihepatotoxic activity

Abstract

Punicic acid of pomegranate oil (PAP) has gained heightened interest due to several health benefits, such as anticarcinogenic, antidiabetic, and antiatherosclerotic properties. However, these bioactivities have been hampered by chemical instability, poor water solubility, rapid metabolism, and low bioavailability of PAP. Therefore, this study was aimed at optimizing the liposomal formulation of Triacylglycerol‐bound punicic acid with its regioisomers (TPAR) for improved oral bioavailability and increased hepatoprotection through antioxidation and anti‐inflammation. Herein, the optimized TPAR nanoliposome (TPAR‐NL) was developed using thin‐film dispersion method and subsequently characterized with appropriate indices. The optimized TPAR‐NL produced fairly stable spherical nanoparticles (˂ 200 nm) with encapsulation efficiency (%EE) of 85.77%, as well as enhanced in vitro release and improved oral bioavailability. The TPAR‐NL exhibited profound antihepatotoxic effect in mice pretreated with carbon tetrachloride (CCl4) via reduction of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels compared with free TPAR. The TPAR‐loaded liposome also significantly reduced oxidative stress by increasing superoxide dismutase and glutathione levels while lowering malonaldehyde concentration compared with the free TPAR. The TPAR‐LNF further exhibited remarkable anti‐inflammatory activity compared with the free drug via inhibition of interleukin‐6 and tumor necrosis factor‐alpha generation. Thus, the developed nanoliposomes potentiated the antihepatotoxic activity of TPAR via antioxidation and anti‐inflammation.

Prevention and Treatment of Methotrexate-induced Hepatotoxicity: Potential of Natural Phytobioactive Compounds<strong> </strong>

“…Natural products and its derived active constituents normally known as phytobioactive compounds have recently been explored in the treatment of several diseases [57][58][59][60]. In recent times, our exploits in phytocompounds research support the assertion that natural products have the potential to prevent and treat oxidative stress-related inflammation which underlie liver disorders [61,62].…”

Novel cuminaldehyde self-emulsified nanoemulsion for enhanced antihepatotoxicity in carbon tetrachloride-treated mice

“…Several conditions and xenobiotics can disrupt the normal functioning of liver . Common xenobiotic used to mimic hepatotoxicity in animal models is carbon tetrachloride (CCl 4 ) which induces oxidative stress, lipid peroxidation and inflammation . Notably, CCl 4 induces injury via its metabolites (trichloromethyl) produced by cytochrome P450 systems .…”

“…Like other natural essential oils (EOs), the use of free cuminaldehyde usually leads to decreased bioactivity because of low bioavailability caused by volatilisation, hydrophobicity and rapid enzymatic metabolisation . Cuminaldehyde could therefore be formulated via appropriate novel techniques to enhance its oral bioavailability and therapeutic efficacy as other natural bioactive compounds . Several reports indicated that carriers such as liposomes, cyclodextrin inclusion complexes and drug‐in‐cyclodextrin‐in‐liposome systems have been used to encapsulate various EOs and their components, viz.…”

“…[18] Common xenobiotic used to mimic hepatotoxicity in animal models is carbon tetrachloride (CCl 4 ) which induces oxidative stress, lipid peroxidation and inflammation. [19,20] Notably, CCl 4 induces injury via its metabolites (trichloromethyl) produced by cytochrome P450 systems. [19] Treatment options which are readily available, biocompatible and effective should be developed for long-term supplementation without any toxicity concerns.…”

“…[24,25] Cuminaldehyde could therefore be formulated via appropriate novel techniques to enhance its oral bioavailability and therapeutic efficacy as other natural bioactive compounds. [20,25,26] Several reports indicated that carriers such as liposomes, cyclodextrin inclusion complexes and drugin-cyclodextrin-in-liposome systems have been used to encapsulate various EOs and their components, viz. clove EO, cinnamaldehyde, thymol, eugenol, trans-ferulic acid, carvacrol, p-cymene, limonene and perillaldehyde.…”