The influence of bile salt on the chemotherapeutic response of docetaxel-loaded thermosensitive nanomicelles

Abstract

The primary aim of this work was to investigate the potential of bile salt, sodium taurocholate (NaTC), in improving the bioavailability and anti-tumor efficacy of docetaxel (DCT) upon rectal administration. Poloxamer-based nanomicelles with thermosensitive and mucoadhesive properties were prepared using the cold method. The optimized nanomicellar formulation was evaluated in terms of physicochemical and viscoelastic parameters. Nanomicelles containing bile salt maintained sufficient gelation strength (234×10 2 mPa·s) and mucoadhesive force (17.3×10 2 dyne/cm 2 ) to be retained in the upper part of the rectum. They significantly enhanced the DCT internalization across the rectal mucosa and showed a high plasma level during the first 4 hours of the study period, compared to nanomicelles with no bile salt. As a result, a slightly higher rectal bioavailability of ~33% was observed in nanomicelles containing bile salt, compared to ~28% from the latter system. The higher pharmacokinetic parameters for rectally administered DCT/P407/P188/Tween 80/NaTC (0.25%/11%/15%/10%/0.1% by weight, respectively) resulted in significant anti-tumor efficacy. However, the tumor regression rate for the NaTC group was not statistically different from that for nanomicelles without NaTC. Therefore, overall results suggest that thermosensitive nanomicelles could be a potential dosage form for improvement of the bioavailability and chemotherapeutic profile of DCT.

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

“…These nanomicelles possessed sufficient viscoelastic properties to remain in the upper part of the rectum for the specified time. They enhanced the absorption of docetaxel across the rectal mucosa and improved its half-life and plasma concentration, resulting in a significant in vivo anti-tumor efficacy ( Kim et al, 2014 ).…”

Absorption-Enhancing Effects of Bile Salts

“…Moreover, the pharmacokinetic results showed that NaTC was influential in improving the half-life and plasma level of DCT. Although the elevated plasma level of DCT from the bile salt group did not enhance the anti-tumor potential, DCT-loaded nanomicelles could reduce the drug-related side effects, such as hypersensitivity reactions and fluid retention, while retaining the potential anti-tumor efficacy in clinical subjects [88].…”

“…Anti-tumor efficacy of DCT-loaded nanomicelles with and without NaTC after rectal administration [88]. * Significantly smaller than control group ( p < 0.01).…”

Nanomedicine-based combination of gambogic acid and retinoic acid chlorochalcone for enhanced anticancer efficacy in osteosarcoma

“…Poorly soluble drugs can be made soluble within the hydrophobic core of the nanoparticles and effectively delivered [12]. Such nanoparticles exhibits important properties including excellent systemic stability, high loading capacity, and preserving the pharmacological property of encapsulated drugs [13].…”