It has been demonstrated that various polymeric surfactants including D-alpha-tocopheryl poly (ethylene glycol) succinate 1000 (commonly known as TPGS), polysorbates (commonly known as Tween) as well as alkyl-PEO (commonly known as Brij) are capable of inhibiting efflux pumps. Brij78 (polyoxyethylene 20 stearylether) had been shown to inhibit the efflux pumps. Scientists have prepared doxorubicin and paclitaxel-loaded nanoparticles using Brij78 as an emulsifying agent to overcome MDR by inhibiting P-gp. Since curcumin had been reported to be a substrate of P-gp and active efflux by P-gp, Brij78 and TPGS, which are commonly used in pharmaceutical formulations as surfactants, provide a good opportunity for enhancing oral bioavailability of curcumin.
In order to improve the solubility and bioavailability of curcumin, scientists have developed a formulation of curcumin solid lipid nanoparticles (Cur-SLNs) containing P-gp modulator excipients, TPGS and Brij78. Cur-SLNs were prepared by emulsification and low-temperature curing. Then the physicochemical properties, entrapment efficiency, and in vitro release of Cur-SLNs were characterized. The effects of Cur-SLNs on curcumin bioavailability and intestinal absorption were studied. The optimized formulation had a mean particle size of about 135.3±1.5 nm and a zeta potential value of 24.7±2.1mV. In vitro release study indicated that Cur-SLNs exhibited a sustained release in SGF and SIF. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. The effect in improving the oral bioavailability of curcumin may result from improving the water solubility, enhancing the absorption by improving the intestinal permeability, inhibiting P-gp-mediated efflux by surfactants, Brij78 and TPGS. Thus, encapsulating drugs on SLNs containing Brij78 and TPGS will be a promising method to improve the bioavailability of the hydrophobic drug, such as curcumin.
Fig.1 Effective permeability coefficient (Peff) of different perfusion solutions. (Ji, 2016)
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