Photo-Cured Glycol Chitosan Hydrogel for Ovarian Cancer Drug Delivery

Abstract

In this study, we prepared an injectable drug delivery depot system based on a visible light-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin (β-CD) (GC/CD/PTX) for ovarian cancer (OC) therapy using a tumor-bearing mouse model. The hydrogel depot system had a 23.8 Pa of storage modulus at 100 rad/s after visible light irradiation for 10 s. In addition, GC was swollen as a function of time. However, GC had no degradation with the time change. Eventually, the swollen GC matrix affected the releases of PTX and CD/PTX. GC/PTX and GC/CD/PTX exhibited a controlled release of PTX for 7 days. In addition, GC/CD/PTX had a rapid PTX release for 7 days due to improved water solubility of PTX through CD/PTX complex. In vitro cell viability tests showed that GC/CD/PTX had a lower cell viability percentage than the free PTX solution and GC/PTX. Additionally, GC/CD/PTX resulted in a superior antitumor effect against OC. Consequently, we suggest that the GC/CD system might have clinical potential for OC therapy by improving the water solubility of PTX, as PTX is included into the cavity of β-CD.

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

“…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].…”

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

“…Although there are some water‐soluble systems for delivering PTX, including TAXOL® and Genexol® PM Injection, they are not the best options because of the lack of proper targeting and usage of a toxic excipient. In addition, other drug delivery systems, such as using nanomaterials and microspheres, which are based on the polymer or lipid, are also not effective due to fast clearance, frequent dosing, insufficient penetration into the tumor, and short half‐life . In order to solve these problems, Hyun et al used a delivery system in which light‐cured glycol chitosan hydrogel, including PTX‐complexed beta‐cyclodextrin (β‐CD), was used.…”

“…In addition, other drug delivery systems, such as using nanomaterials and microspheres, which are based on the polymer or lipid, are also not effective due to fast clearance, frequent dosing, insufficient penetration into the tumor, and short half‐life . In order to solve these problems, Hyun et al used a delivery system in which light‐cured glycol chitosan hydrogel, including PTX‐complexed beta‐cyclodextrin (β‐CD), was used. CP is another chemotherapy drug used in ovarian cancer, although there are multiple problems in using this drug, such as its poor solubility in both water and oil phases, high toxicity in healthy tissues caused in its administration intravenously, and rapid clearance caused by its low molecular weight in intravenous administration .…”