In vivo pharmacokinetics, biodistribution and antitumor effect of paclitaxel-loaded micelles based on α-tocopherol succinate-modified chitosan

Abstract

In our previous study, a-tocopherol succinate modified chitosan (CS-TOS) was synthesized and encapsulated paclitaxel (PTX) to form micelles. Preliminary study revealed that the CS-TOS was a potential micellar carrier for PTX. In this study, some further researches were done using Taxol formulation as the control to evaluate the micelle system deeply. In vitro cell experiments demonstrated that the cytotoxic effect of PTX-loaded CS-TOS micelles against MCF-7 cells was comparable with that of Taxol formulation, and the PTX-loaded micelles had excellent cellular uptake ability, which was in a time-dependent manner. The in vivo pharmacokinetic study in rats showed that the micelles prolonged the half-life and increased AUC of PTX than Taxol formulation. From biodistribution study, it was clear that for micelles, the drug concentrations in the liver and spleen were significantly higher than those of Taxol formulation, but much lower in the heart and kidney. Furthermore, the PTX-loaded micelles showed superior antitumor effect, but yielded less toxicity as indicated by the results of antitumor efficacy study and survival study in U14 tumor-bearing mice. These results suggested that CS-TOS micelles could be a potentially useful drug delivery system to improve the performance and safety of PTX.

Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

“…The in vivo antitumor activity of PTX-loaded FA-CS-DA micelles was evaluated in H22 tumor-bearing mice. To establish the tumor model, mice were inoculated subcutaneously in the right armpit with 5 × 10 6 cells (0.2 mL) [ 36 ]. When the tumor xenografts became palpable, the mice were randomly divided into 2 groups ( n = 6) and treated with physiological saline and PTX-loaded FA-CS-DA micelles (15 mg/kg), respectively.…”

Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration

“…For example, the micellar formulations, NK911 and Genexol-PM, have already advanced to the clinical trials (Matsumura, 2006;Ahn et al, 2014). Thanks to their distinctive core-shell structure, polymeric micelles possess high loading capacity of poorly water-soluble drugs within the hydrophobic inner core; whereas the hydrophilic corona confers aqueous solubility and steric stability, which also protects the encapsulated drug from inactivation in gastrointestinal components (Croy & Kwon, 2006;Liang et al, 2015). Importantly, due to the small size of micelles, previous reports described that the drugloaded nanoparticles could be absorbed in intact form by enterocytes or M cells via endocytic pathway after oral administration (Mathot et al, 2007;Li et al, 2010;Al-Hilal et al, 2013).…”

Indomethacin-based stimuli-responsive micelles combined with paclitaxel to overcome multidrug resistance

“…To determine the accumulated PTX in tumors and normal tissues at 24 and 48 h after intravenous administration of PTX-based formulations at 10 mg/kg PTX equivalent, the tissue samples were processed according to the previous study by Liang et al [ 21 ] and the results were shown in Figure 5C . After administration for 24 and 48 h, the accumulations of DEX-IND/PTX and DEX-SS-IND/PTX in tumors were significantly enhanced compared with Taxol.…”