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In Situ Thermoresponsive Hydrogel: A Novel Approach for Intratumoral Injection in Cancer Therapy

  • R. Martins,
  • J. Seixas,
  • P. Cal,
  • J. Marto

摘要

In recent years, thermoresponsive hydrogels have emerged as a promising option for controlled-release drug delivery systems, particularly in cancer therapy [1]. These hydrogels undergo a transition from a liquid to a gel state in response to temperature changes, facilitating localized and sustained release of anticancer drugs [2]. Localized intratumoral injections have gained popularity due to their ability to deliver therapeutic agents directly to the tumor site, reducing systemic exposure and associated side effects [3]. This study aims to explore the use of a thermoresponsive hydrogel for intratumoral injections in cancer therapy by achieving an optimal sol-gel transition temperature. To accomplish that, characterization of the thermoresponsive hydrogels was performed using rheological analysis (Kinexus Lab + Rheometer; Malvern Instruments, UK) to determine the oscillatory sol-gel transition temperature (Tsol-gel), dynamic viscosity, adhesivity, and mucoadhesive forces. The Tsol-gel was identified by the crossover point between the elastic modulus (G’) and the viscous modulus (G’’) at which the sample exhibited a switch from a prevalently viscous behavior (G’’ > G’) to a prevalently elastic one (G’ > G’’). In vitro release studies (IVRT) were also performed to acquire the anti-cancer drug release profile. It was possible to obtain a thermoreversible hydrogel formulated with a mixture of poloxamers at specific concentrations, with a Tsol-gel between room and physiological temperatures. The addition of BioP did not significantly alter Tsol-gel (p > 0.05), but it improved adhesion significantly (p < 0.05). Sol-gel temperature optimized at 20–28 ℃ with controlled release for 30 h, paving the way for further exploration of hydrogels in cancer therapy.