Potent Paclitaxel Research Articles

Applying quality by design approach for the determination of potent paclitaxel loaded poly(lactic acid) based implants for localized tumor drug delivery

In the present study, poly(lactic acid) (PLA) and poly(ethylene succinate) (PESu) or poly(ethylene glycol) (PEG) under the framework of quality by design, were blended to produce effective sustained-release matrices for Paclitaxel delivery. A complete physicochemical characterization including weight variation, thickness, water uptake, moisture absorption, moisture loss, and hydrolytic degradation under physiological conditions, was performed. Quality by design approach was applied to study the critical parameters. In vitro cancer toxicity was studied in human cancer cell lines including lung and breast adenocarcinoma. The developed Paclitaxel-loaded films can act as a promising alternative topical matrix as an implant for breast and lung cancer treatment.

Development of Safe and Potent Oil-in-Water Emulsion of Paclitaxel to Treat Peritoneal Dissemination

To develop a safer and more potent paclitaxel (PTX) formulation, we prepared various oil-in-water emulsions by using egg phosphatidylcholine, Tween 80, and a mixture of triglycerides with different fatty acid chain lengths as the cosurfactant, surfactant, and oil phase component, respectively. The mean particle diameters of the PTX-emulsions prepared were around 100 nm. The PTX-emulsions did not provoke histamine release from rat mast cells and did not show any significant hemolytic activity, suggesting that PTX-emulsions are biocompatible. In vivo antitumor activity after single intraperitoneal injection of PTX-emulsions to ascites tumor-bearing mice revealed that the formulation containing tricaproin and triacetin (3:1, wt/wt, PTX-emulsion B) significantly prolonged the survival time and suppressed the accumulation of ascites fluid. Two distinct in vitro release studies showed that the release of PTX from emulsion B was significantly faster than those from other preparations. These results indicate that the adequately sustained PTX release would lead to potent in vivo antitumor activity and that PTX-emulsion B would offer an alternative approach to treat peritoneal dissemination.

Paclitaxel-loaded stealth liposomes: Development, characterization, pharmacokinetics, and biodistribution

Aim In the present paper, paclitaxel (PTX)-loaded stealth liposomes were prepared with thin film hydration technique in order to prolong the time of circulation. Method The liposomes’ characterization, in vitro release, pharmacokinetics, and biodistribution profile of the drug were investigated. Results Microscope showed that the liposomes were spherical in shape with a smooth surface and the size was uniform and appropriate for administration via intravenous injection. The encapsulation efficiency was 91.1 ± 4.3%, and the mean diameter was 82.2 ± 7.6 nm from three batches. The results of in vivo studies indicated that PTX-loaded stealth liposomes show favorable pharmacokinetics and biodistribution compared to the free drug. In comparison with free PTX, the AUC0-t of PTX liposomes and stealth liposomes increased 1.91- and 3.39-fold, respectively. The stealth liposomes were long-circulating showing a half-life time of 34.2 h against 13.7 h for the conventional ones. Conclusions These results suggest that stealth liposomes would serve as a potent PTX delivery vehicle for the future cancer chemotherapy and represent a suitable platform for the development of targeted liposomal PTX systems.

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80 nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.

PEG liposomalization of paclitaxel improved its in vivo disposition and anti-tumor efficacy

To find out potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX in O/W emulsion and liposome selected as candidates of nanocarriers for PTX. Surface modification of these nanoparticles with polyethylene glycol (PEG) improved their in vivo behavior, but the effect of PEGylation on the pharmacokinetics of emulsion was not so remarkable and the release of PTX from emulsion was found to be very fast in blood circulation, indicating that emulsion would not be an adequate formulation for PTX. On the other hand, AUC of PEG liposome was 3.6 times higher than that of naked liposome after intravenous injection into normal rats due to the lower disposition into the reticuloendothelial system tissues such as liver and spleen. Since PEG liposome was able to stably encapsulate PTX in blood, AUC of PTX was also extensively enhanced after intravenous dosing of PTX-PEG liposome into normal rats. In the in vivo studies utilizing Colon-26 solid tumor-bearing mice, it was confirmed that PTX-PEG liposome delivered significantly larger amount of PTX to tumor tissue and provided more excellent anti-tumor effect than PTX-naked liposome. These results suggest that PEG liposome would serve as a potent PTX delivery vehicle for the future cancer chemotherapy.