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Antitumoral effect and reduced systemic toxicity in mice after intra-tumoral injection of an in vivo solidifying calcium sulfate formulation with docetaxel
LIDDS AB, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.ORCID iD: 0000-0002-0370-8819
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2017 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 114, 186-193 p.Article in journal (Refereed) Published
Abstract [en]

Background

Docetaxel is a cytostatic agent approved for treatment of non-small cell lung cancer as well as other cancers. Although docetaxel is an effective cytostatic agent, its effectiveness in clinical practice is associated with a variety of acute and long term side-effects. To overcome systemic side-effects, a slow release formulation based on calcium sulfate with docetaxel for intra-tumoral administration was developed.

Methods

Two formulations with the calcium sulfate NanoZolid technology were generated with a twofold difference in docetaxel drug load. The formulations were injected intra-tumorally as a paste which solidified within the tumor. The effects of the two intra-tumoral injection formulations were tested in female mice (n = 60) inoculated with subcutaneous Lewis lung carcinoma cells. The two formulations were compared to systemic intraperitoneal injection of docetaxel and a placebo formulation without docetaxel. Tumor volumes were measured and systemic side-effects were evaluated using body weight and cell counts from whole blood as well as plasma concentrations.

Results

Both docetaxel formulations showed a significantly higher antitumor efficacy compared to placebo, which was comparable to that of systemic administration of docetaxel. Moreover, the intra-tumoral formulations with docetaxel showed reduced systemic toxicity compared to systemic treatment, including less weight loss and no decrease in blood cell counts.

Conclusions

The results suggest that intra-tumoral slow release calcium sulfate based formulations with docetaxel can be an alternative strategy as an efficient local antitumoral treatment with reduced systemic toxicity.

Place, publisher, year, edition, pages
2017. Vol. 114, 186-193 p.
Keyword [en]
Bioresorbable, Calcium sulfate, Docetaxel, Intratumoral, Lewis lung carcinoma, Non-small cell lung cancer, Slow release formulation
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-316552DOI: 10.1016/j.ejpb.2017.01.018ISI: 000399268900019PubMedID: 28161551OAI: oai:DiVA.org:uu-316552DiVA: diva2:1078177
Funder
Magnus Bergvall Foundation, 24942-1-2013Magnus Bergvall Foundation, 214-00055Swedish Research Council, 521-2012-865Åke Wiberg Foundation, 738866289
Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-05-23Bibliographically approved

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The full text will be freely available from 2018-05-01 00:00
Available from 2018-05-01 00:00

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Sandelin, MartinMicke, PatrickHedeland, MikaelJeansson, Marie

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Respiratory Medicine and AllergologyDepartment of Immunology, Genetics and PathologyAnalytical Pharmaceutical ChemistryVascular Biology
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European journal of pharmaceutics and biopharmaceutics
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