Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model

Vassileva, Vessela; Grant, Justin; Souza, Raquel De; Allen, Christine; Piquette-Miller, Micheline

doi:10.1007/s00280-007-0449-0

Cited by 61 publications

(46 citation statements)

References 11 publications

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“…The diminished toxicity and enhanced efficacy with PTX ePC was also reflected by the lack of significant changes in body weight. Indeed, we have previously demonstrated favourable toxicity profiles with PTX ePC and augmented toxicity with Taxol (Vassileva et al, 2007). Similarly, weight loss may be reflective of efficacy, as physical wasting is an attribute of disease progression with this model.…”

Section: Discussionmentioning

confidence: 99%

“…bolus injections of 20 mg kg À1 Taxol s on a q7d Â 3 schedule) or sustained therapy (PTX ePC surgically implanted i.p., providing sustained delivery of 20 mg kg À1 per week) and were compared with controls (drug-free ePC implant). Prior to treatment initiation, release from PTX ePC was confirmed both in vitro and in vivo as described earlier (Grant et al, 2005;Ho et al, 2005;Vassileva et al, 2007). Treatment was initiated 7 days post SKOV3 Luc inoculation, referred to as Day 0; on this date, three mice were killed for visual and microscopic tumour inspection/analysis, and the remainder of the animals (n ¼ 36), were separated into the various groups as described above (n ¼ 12/each group).…”

Section: Treatment Groupsmentioning

confidence: 99%

“…Plasma, tumour and liver drug concentrations were measured by high performance liquid chromatography as described earlier (Vassileva et al, 2007). As intraperitoneal ovarian xenografts disseminate throughout the peritoneal cavity, all macroscopic (visible) tumour nodules were excised, harvested and weighed, followed by fixation in 4% paraformaldehyde (PFA) solution.…”

Section: Treatment Groupsmentioning

confidence: 99%

“…Therefore more tolerable therapeutic interventions are required and in this context, we developed a novel implantable paclitaxel drug delivery system (PTX ePC ). Our initial studies demonstrated that PTX ePC provided local and controlled release of PTX over several weeks and that it was safer and better tolerated than commercially available PTX formulated in Cremophor EL (Grant et al, 2005;Ho et al, 2005;Vassileva et al, 2007).…”

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confidence: 99%

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Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

et al. 2008

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We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTX ePC ) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3 Luc ) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol s , sustained PTX ePC therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTX ePC implant system, which could potentially translate into successful clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Treatment Groupsmentioning

confidence: 99%

Section: Treatment Groupsmentioning

confidence: 99%

mentioning

confidence: 99%

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Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

et al. 2008

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“…We previously developed an implantable polymer-lipid film capable of continuous release of paclitaxel, which showed efficacy in an ovarian cancer xenograft model (13,14). The need for surgical implantation and slow biodegradation led to the development of an injectable paste with similar properties composed of chitosan, phospholipids, and laurinaldehyde, termed PoLi gel , which showed good biocompatibility and biodegradation (15,16).…”

Section: Introductionmentioning

confidence: 99%

Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer

Souza

Zahedi

Moriyama

et al. 2010

Molecular Cancer Therapeutics

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Ovarian cancer is known as the silent killer for being asymptomatic until late stages. Current first-line treatment consists of debulking surgery followed by i.v. chemotherapeutics administered intermittently, which leads to insufficient drug concentrations at tumor sites, accelerated tumor proliferation rates, and drug resistance, resulting in an overall median survival of only 2 to 4 years. For these reasons, more effective treatment strategies must be developed. We have investigated a localized, continuous chemotherapy approach in tumor models of human and murine ovarian cancers using the antineoplastic agent docetaxel. We show here that continuous docetaxel therapy is considerably more efficacious than intermittent therapy, resulting in a greater decrease in tumor burden and ascites fluid accumulation. Immunohistochemical analyses show that continuous chemotherapy abrogates tumor cell proliferation and angiogenesis to the tumor microenvironment, leading to greater tumor cell death than intermittent docetaxel therapy. Overall, our results show greater therapeutic advantages of continuous over intermittent chemotherapy in the treatment of ovarian cancer.

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Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

Dumitriu¹,

Oprea²,

Cheaburu-Yılmaz³

et al. 2014

J of Applied Polymer Sci

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Mixed-interpenetrated polymeric networks based on sodium alginate (ALG) and poly(N-isopropylacryl amide) (PNI-PAAm) covalently cross-linked with N,N'-methylenebisacrylamide are studied for their biocompatibility, nontoxicity, and biodegradability aiming their application in drug delivery. The presence of drug-polymeric matrix interactions and the distribution of the drug in the polymeric network for theophylline-loaded ALG/PNIPAAm hydrogels are also investigated by spectroscopic and microscopic methods. The quantitative evaluation of theophylline loaded hydrogels performed by NIR-CI technique shows a better drug entrapment and a higher homogeneity of the samples with increased alginate content. The thermal behavior of the hydrogels is significantly modified by theophylline presence. The application of the ALG/PNIPAAm hydrogels as carriers for sustained drug release formulations was assessed by the theophylline release tests performed both by in vitro and in vivo studies. V C 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40733.

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Novel biocompatible intraperitoneal drug delivery system increases tolerability and therapeutic efficacy of paclitaxel in a human ovarian cancer xenograft model

Abstract: The novel PTX(ePC) formulation is a safer and better tolerated method for PTX administration, with significant increase in MTD and enhanced anti-tumour efficacy, suggesting improved therapeutic index with possible clinical implications in the treatment of ovarian tumours.

Cited by 61 publications

References 11 publications

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging

Continuous Docetaxel Chemotherapy Improves Therapeutic Efficacy in Murine Models of Ovarian Cancer

Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

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