Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer.

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Chantal Al SabbaghNathalie Mignet

Abstract

Spurred by high risk for local tumor recurrence and non-specific toxicity of systemic chemotherapy, clinicians have recently granted a growing interest to locoregional therapeutic strategies. In this perspective, we recently developed a multipurpose thermosensitive hydrogel based on reversible thermogelling properties of poloxamers P407 and P188, a bioadhesive excipient and antineoplastic effect of 5-fluorouracil (5-FU) for the local treatment of colorectal cancer (CRC) in ectopic CT26 murine models. Antitumor efficacy was assessed in mice following intratumoral (IT) injection mimicking neoadjuvant therapy and subcutaneous (SC) application after tumor excision simulating adjuvant therapy. Rheological characterization disclosed that P407/P188/alginate 20/2/1% w/v thermosensitive hydrogel is an injectable free-flowing solution at ambient temperature that undergoes a SOL-GEL transition at 26.0 °C ± 0.6 °C and thereby forms in situ a non-flowing gel at physiological temperature. The generated gel presented an elastic behavior and responded according to a shear-thinning fluid upon shear rate. Although delayed by the addition of alginate 1% w/v, 5-FU is released mainly by diffusion mechanism. The local delivery of 5-FU from P407/P188...Continue Reading

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Citations

Dec 29, 2020·Frontiers in Chemistry·Elise LepeltierYohann Corvis
Mar 9, 2021·Langmuir : the ACS Journal of Surfaces and Colloids·Évelin L de OliveiraWilker Caetano
Sep 3, 2021·European Journal of Pharmacology·Shadma WahabHashim Abbas

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