In vitro cytotoxicity of paclitaxel/β-cyclodextrin complexes for HIPEC

Bouquet, Wim; Boterberg, Tom; Ceelen, Wim; Pattyn, Piet; Peeters, Marc; Bracke, Marc; Remon, Jean Paul; Vervaet, Chris

doi:10.1016/j.ijpharm.2008.09.035

Cited by 29 publications

(17 citation statements)

References 22 publications

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“…The cytotoxicity of the test formulations was determined via MTT assay and compared with the nontreated cells (14). Afterwards, the optical density was measured at 570 nm normalizing with a reference wavelength of 650 nm using an ELISA-plate reader (Paradigm Detection Platform, Beckman Coulter, Suarleé, Belgium).…”

Section: Nanocrystal Characterizationmentioning

confidence: 99%

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

et al. 2012

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Purpose: To develop a nanocrystalline paclitaxel formulation with a high paclitaxel-to-stabilizer ratio which can be used for hyperthermic intraperitoneal chemotherapy (HIPEC).Methods: Paclitaxel (PTX) nanocrystals were prepared via wet milling using Pluronic F127 ® as stabilizer. The suitability of paclitaxel nanosuspensions for HIPEC treatment was evaluated by analyzing the cytotoxicity of both stabilizer and formulation, and by determining the maximum tolerated dose (MTD) and bioavailability. The effect on tumor growth was evaluated by magnetic resonance imaging (MRI) at day 7 and 14 after HIPEC treatment in rats with peritoneal carcinomatosis of ovarian origin.Results: Monodisperse nanosuspensions (±400 nm) were developed using Pluronic F127 ® as single additive. The cytotoxicity and MTD of this nanocrystalline formulation was similar compared to Taxol ® , while its bioavailability was higher. MRI data after HIPEC treatment with a PTX nanocrystalline suspension showed a significant reduction of tumor volume compared to the nontreated group. Although no significant differences on tumor volume were observed between Taxol ® and the nanosuspension, the rats treated with the nanosuspension recovered faster following the HIPEC procedure.Conclusion: Nanosuspensions with a high paclitaxel-to-stabilizer ratio are of interest for the treatment of peritoneal carcinomatosis of ovarian origin via HIPEC.

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Section: Nanocrystal Characterizationmentioning

confidence: 99%

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

et al. 2012

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“…Cyclodextrins have been extensively used to enhance the solubility, mask bitterness, improve stability, improve bioavailability, and decrease tissue irritation upon administration of a variety of poorly soluble drugs (13)(14)(15). Cyclodextrins have been shown to increase the cytotoxicity of several antineoplastic drugs like camptothecin (16,17), curcumin (18), doxorubicin, docetaxel (19), paclitaxel (20), etc. SN-38-βCD complex has been used to prepare in situ polymeric implants (21), but there was no detailed study reported on the effect of CDs on improving solubility, stability, and cytotoxicity of SN-38.…”

Section: Introductionmentioning

confidence: 99%

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

Vangara

Ali

et al. 2014

AAPS PharmSciTech

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Abstract. SN-38, an active metabolite of irinotecan, is up to 1,000-fold more potent than irinotecan. But the clinical use of SN-38 is limited by its extreme hydrophobicity and instability at physiological pH. To enhance solubility and stability, SN-38 was complexed with different cyclodextrins (CDs), namely, sodium sulfobutylether β-cyclodextrin (SBEβCD), hydroxypropyl β-cyclodextrin, randomly methylated β-cyclodextrin, and methyl β-cyclodextrin, and their influence on SN-38 solubility, stability, and in vitro cytotoxicity was studied against ovarian cancer cell lines (A2780 and 2008). Phase solubility studies were conducted to understand the pattern of SN-38 solubilization. SN-38-βCD complexes were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction analysis (XRPD), and Fourier transform infrared (FTIR). Stability of SN-38-SBEβCD complex in pH 7.4 phosphate-buffered saline was evaluated and compared against free SN-38. Phase solubility studies revealed that SN-38 solubility increased linearly as a function of CD concentration and the linearity was characteristic of an A P -type system. Aqueous solubility of SN-38 was enhanced by about 30-1,400 times by CD complexation. DSC, XRPD, and FTIR studies confirmed the formation of inclusion complexes, and stability studies revealed that cyclodextrin complexation significantly increased the hydrolytic stability of SN-38 at physiological pH 7.4. Cytotoxicity of SN-38-SBEβCD complex was significantly higher than SN-38 and irinotecan in both A2780 and 2008 cell lines. Results suggest that SBEβCD encapsulated SN-38 deep into the cavity forming stable inclusion complex and as a result increased the solubility, stability, and cytotoxicity of SN-38. It may be concluded that preparation of inclusion complexes with SBEβCD is a suitable approach to overcome the solubility and stability problems of SN-38 for future clinical applications.

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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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In vitro cytotoxicity of paclitaxel/β-cyclodextrin complexes for HIPEC

Cited by 29 publications

References 22 publications

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

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

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In vitro cytotoxicity of paclitaxel/β-cyclodextrin complexes for HIPEC

Cited by 29 publications

References 22 publications

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

Development of a Nanocrystalline Paclitaxel Formulation for Hipec Treatment

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

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

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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