In recent years, mucoadhesivein situ gelling formulations for intravesical application have been studied to improve the therapeutic outcomes of bladder cancer patients. Here, we carefully tuned a Pluronic F127-based thermoresponsive gel using two mucoadhesive thiolated derivatives of glycol chitosan, S-preactivated N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC). The gel was loaded with a combination of Gemcitabine (GEM) and Celecoxib (CEX), and the aqueous solubility of the latter was increased for a synergic influence between Pluronic and the inclusion complex of 2-Hydroxypropyl-& beta;-cyclodextrin/CEX. The effect of the inclusion complex of two mucoadhesive polymers on rheological features of Pluronic based gels was highlighted to select the best performance. Finally, ex-vivo retention studies, mucosal penetration and in-vitro drug release of the selected systems were monitored for 24 h, providing enhanced retention properties (50% after 6 h) and continued drug release.
Thermoresponsive mucoadhesive hydrogel based on Pluronic F127/ thiolated glycol chitosan for intravesical administration of celecoxib/ gemcitabine
Racaniello, GF;Denora, N;Gentile, LMembro del Collaboration Group
;Lopalco, A;Cutrignelli, AMembro del Collaboration Group
;Franco, MMembro del Collaboration Group
;Iacobazzi, RM;Laquintana, V;Lopedota, A
2023-01-01
Abstract
In recent years, mucoadhesivein situ gelling formulations for intravesical application have been studied to improve the therapeutic outcomes of bladder cancer patients. Here, we carefully tuned a Pluronic F127-based thermoresponsive gel using two mucoadhesive thiolated derivatives of glycol chitosan, S-preactivated N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC). The gel was loaded with a combination of Gemcitabine (GEM) and Celecoxib (CEX), and the aqueous solubility of the latter was increased for a synergic influence between Pluronic and the inclusion complex of 2-Hydroxypropyl-& beta;-cyclodextrin/CEX. The effect of the inclusion complex of two mucoadhesive polymers on rheological features of Pluronic based gels was highlighted to select the best performance. Finally, ex-vivo retention studies, mucosal penetration and in-vitro drug release of the selected systems were monitored for 24 h, providing enhanced retention properties (50% after 6 h) and continued drug release.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.