Injectable visible light-cured glycol chitosan hydrogels with controlled release of anticancer drugs for local cancer therapy in vivo: a feasible study

Abstract

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time. In addition, the swelling ratio of the hydrogel irradiated for 10 s (GC/DOX) was greater than in 60 s (GC/DOX). In vitro release test showed that DOX was rapidly released in GC/DOX compared with GC/DOX due to the density of cross-linking. In vitro and in vivo tests including cell viability and measurement of tumor volume showed that the local treatment of GC/DOX yielded substantially greater antitumor effect compared with that of GC/DOX. Therefore, the visible light-cured GC hydrogel system may exhibit clinical potential as a local DDS of anticancer drugs with controlled release, by modulating cross-linking density.

Doxorubicin·Hydrochloride/Cisplatin-Loaded Hydrogel/Nanosized (2-Hydroxypropyl)-Beta-Cyclodextrin Local Drug-Delivery System for Osteosarcoma Treatment In Vivo

“…Among hydrogel systems, an injectable hydrogel is valuable, both because it can directly deliver anticancer drugs near cancer tissues by local injection and because it has a potential for drug loading in the matrices. In our previous studies, the visible light-cured GC hydrogel system was found to be a potent local drug-delivery carrier because of its injectability and the fact that it allows anticancer drugs to be controllably released in a sustained manner [10][11][12].…”

“…We have previously reported that the GC hydrogel has porous structure together with interconnectivity [10][11][12]. These structural properties resulted in in vivo anticancer effects against solid cancers when the GC hydrogel was used as the local anticancer drug-delivery system [10][11][12]. Therefore, it is assumed that GDHCP has a superior anticancer effect against osteosarcoma in vitro and in vivo (Figures 3-8).…”

“…The methacrylic group was conjugated to GC for photo-curing [10][11][12]. GC (0.003 mmol, 1.5 g) was dissolved in water (500 mL).…”

“…Although systemic drug-delivery systems are efficient, their therapeutic applications are sometimes limited by complicated preparation. Hydrogel-medicated local drug delivery systems are capable of directly delivering anticancer drugs to targeted sites without complicated procedures because they can be implanted near cancer tissues [10][11][12]. We have already reported that a visible light-cured injectable glycol chitosan (GC) hydrogel-based local drug-delivery system can be used as an anticancer drug carrier for treatment of several solid cancers [10][11][12].…”

“…Hydrogel-medicated local drug delivery systems are capable of directly delivering anticancer drugs to targeted sites without complicated procedures because they can be implanted near cancer tissues [10][11][12]. We have already reported that a visible light-cured injectable glycol chitosan (GC) hydrogel-based local drug-delivery system can be used as an anticancer drug carrier for treatment of several solid cancers [10][11][12]. Additionally, beta-cyclodextrin (β-CD) is used as a nanosized drug carrier for anticancer drugs because it has a cavity that is similar in size to the drugs [13,14].…”