Paclitaxel/β-cyclodextrin complexes for hyperthermic peritoneal perfusion – Formulation and stability

Bouquet, Wim; Ceelen, Wim; Fritzinger, Bernd; Pattyn, Piet; Peeters, Marc; Remon, Jean Paul; Vervaet, Chris

doi:10.1016/j.ejpb.2006.11.025

Cited by 54 publications

(28 citation statements)

References 15 publications

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“…36 Another reason for the hesitancy toward the use of hyperthermia, alone or as PTX sensitizer, can be attributed to conflicting outcomes of preclinical studies. 31,[37][38][39] However, these differences can be explained by the substantial variations in the HT protocols applied (e.g., temperature, length of HT treatment, concentration, and length of PTX exposure).…”

Section: Introductionmentioning

confidence: 99%

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

et al. 2013

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Microtubule-poisoning drugs, such as Paclitaxel (or taxol, PtX), are powerful and commonly used anti-neoplastic agents for the treatment of several malignancies. PtX triggers cell death, mainly through a mitotic arrest following the activation of the spindle assembly checkpoint (SAC). Cells treated with PtX slowly slip from this mitotic block and die by mitotic catastrophe. However, cancer cells can acquire or are intrinsically resistant to this drug, posing one of the main obstacles for PtX clinical effectiveness. In order to override PtX resistance and increase its efficacy, we investigated both the enhancement of mitotic slippage and the block of mitotic exit.to test these opposing strategies, we used physiological hyperthermia (Ht) to force exit from PtX-induced mitotic block and the anaphase-promoting complex/cyclosome (APC/C) inhibitor, protAMe, to block mitotic exit. We observed that application of Ht on PtX-treated cells forced mitotic slippage, as shown by the rapid decline of cyclin B levels and by microscopy analysis. Similarly, Ht induced mitotic exit in cells blocked in mitosis by other antimitotic drugs, such as Nocodazole and the Aurora A inhibitor MLN8054, indicating a common effect of Ht on mitotic cells. On the other hand, protAMe prevented mitotic exit of PtX and MLN8054 arrested cells, prolonged mitosis, and induced apoptosis. In addition, we showed that protAMe prevented Ht-mediated mitotic exit, indicating that stress-induced APC/C activation is necessary for Ht-induced mitotic slippage.Finally, Ht significantly increased PtX cytotoxicity, regardless of cancer cells' sensitivity to PtX, and this activity was superior to the combination of PtX with pro-tAMe. Our data suggested that forced mitotic exit of cells arrested in mitosis by anti-mitotic drugs, such as PtX, can be a more successful anticancer strategy than blocking mitotic exit by inactivation of the APC/C.

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Section: Introductionmentioning

confidence: 99%

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

et al. 2013

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“…New formulations that overcome these problems will have clear clinical advantages. In recent years, various groups of researchers have investigated the development of novel formulations for PTX, including liposomes, [10][11][12][13][14][15] emulsions, [16][17][18][19] cyclodextrins, [20][21][22] microspheres, 23,24 nanoparticles, [25][26][27][28][29][30][31] and implants. [32][33][34][35] In addition, injectable thermoreversible hydrogels are also being developed with reasonable success for PTX delivery.…”

Section: Introductionmentioning

confidence: 99%

Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies

Nie¹,

Hsiao²,

Pan³

et al. 2011

IJN

119

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Purpose To develop an in situ gel system comprising liposome-containing paclitaxel (PTX) dispersed within the thermoreversible gel (Pluronic ® F127 gel) for controlled release and improved antitumor drug efficiency. Methods The dialysis membrane and membrane-less diffusion method were used to investigate the in vitro drug release behavior. Differential scanning calorimetry (DSC) thermal analysis was used to investigate the “micellization” and “sol/gel transition” process of in situ gel systems. In vitro cytotoxicity and drug uptake in KB cancer cells were determined by MTT, intercellular drug concentration, and fluorescence intensity assay. Results The in vitro release experiment performed with a dialysis membrane model showed that the liposomal gel exhibited the longest drug-release period compared with liposome, general gel, and commercial formulation Taxol ® . This effect is presumably due to the increased viscosity of liposomal gel, which has the effect of creating a drug reservoir. Both drug and gel release from the in situ gel system operated under zero-order kinetics and showed a correlation of release of PTX with gel, indicating a predominating release mechanism of the erosion type. Dispersing liposomes into the gel replaced larger gel itself for achieving the same gel dissolution rate. Both the critical micelle temperature and the sol/gel temperature, detected by DSC thermal analysis, were shifted to lower temperatures by adding liposomes. The extent of the shifts depended on the amount of embedded liposomes. MTT assay and drug uptake studies showed that the treatment with PTX-loaded liposomal 18% Pluronic F127 yielded cytotoxicities, intercellular fluorescence intensity, and drug concentration in KB cells much higher than that of conventional liposome, while blank liposomal 18% Pluronic F127 gel was far less than the Cremophor EL ® vehicle and empty liposomes. Conclusions A thermosensitive hydrogel with embedded liposome is a promising carrier for hydrophobic anticancer agents, to be used in parenteral formulations for treating local cancers.

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“…abdominal pain) and life-threatening hypersensitivity reactions, prompting the need for a new and safer paclitaxel formulation (6,8). Therefore, previously a cosolvent-and tensioactive-free paclitaxel formulation was developed consisting of Pac/randomly methylated-β-cyclodextrins (RAME-β-CD) inclusion complexes, which are dissolved in a phosphate-buffered saline solution with 0.1% hydroxypropylmethylcellulose (HPMC) (9). This cyclodextrinbased paclitaxel formulation (Pac/RAME-β-CD) showed an in-vitro antitumour efficacy similar to Taxol®, while RAME-β-CD was significantly less cytotoxic compared to Cremophor EL (10).…”

Section: Introductionmentioning

confidence: 99%

Antitumour Efficacy of Two Paclitaxel Formulations for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in an In Vivo Rat Model

et al. 2011

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Paclitaxel/β-cyclodextrin complexes for hyperthermic peritoneal perfusion – Formulation and stability

Cited by 54 publications

References 15 publications

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies

Antitumour Efficacy of Two Paclitaxel Formulations for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in an In Vivo Rat Model

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Paclitaxel/β-cyclodextrin complexes for hyperthermic peritoneal perfusion – Formulation and stability

Cited by 54 publications

References 15 publications

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy

Thermoreversible Pluronic&reg; F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies

Antitumour Efficacy of Two Paclitaxel Formulations for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in an In Vivo Rat Model

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Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies