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Co-delivery of natural metabolic inhibitors in a self-microemulsifying drug delivery system for improved oral bioavailability of curcumin.

Drug delivery and translational research (2014-11-26)
Alex E Grill, Brenda Koniar, Jayanth Panyam
ABSTRACT

In spite of its well-documented anticancer chemopreventive and therapeutic activity, the clinical development of curcumin has been limited by its poor oral bioavailability. Curcumin has low aqueous solubility and undergoes extensive first pass metabolism following oral dosing. We hypothesized that oral bioavailability of curcumin can be enhanced by increasing its absorption and decreasing its metabolic clearance simultaneously. To test this hypothesis, we formulated curcumin with naturally occurring UGT inhibitors (piperine, quercetin, tangeretin, and silibinin) in a self-microemulsifying drug delivery system (SMEDDS). Mouse liver microsome studies showed that silibinin and quercetin inhibited curcumin glucuronidation effectively. When dosed orally in mice, the SMEDDS containing curcumin alone increased curcumin glucuronide concentrations in plasma without significantly affecting parent drug concentration. Of the four inhibitors examined in vivo, silibinin significantly improved the Cmax (0.15 μM vs. 0.03 μM for curcumin SMEDDS) and the overall bioavailability (3.5-fold vs. curcumin SMEDDS) of curcumin. Previous studies have shown that silibinin has anticancer activity as well. Thus, co-delivery of silibinin with curcumin in SMEDDS represents a novel and promising approach to improve curcumin bioavailability.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
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Acetonitrile, anhydrous, 99.8%
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Dimethyl sulfoxide, sterile-filtered, BioPerformance Certified, meets EP, USP testing specifications, suitable for hybridoma
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Quercetin, ≥95% (HPLC), solid
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Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
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Curcumin, from Curcuma longa (Turmeric), powder
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(−)-Epigallocatechin gallate, ≥95%
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Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
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Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
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Curcumin, ≥94% (curcuminoid content), ≥80% (Curcumin)
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Uridine, ≥99%
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Uridine, powder, BioReagent, suitable for cell culture
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Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
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Piperine, ≥97%
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Dimethyl sulfoxide, PCR Reagent
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Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC
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(−)-Epigallocatechin gallate, ≥80% (HPLC), from green tea
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Uridine, BioUltra, ≥99%
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Acetonitrile, electronic grade, 99.999% trace metals basis
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