RESUMO
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 (ß-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 ß-CD.
Assuntos
Quitina/análogos & derivados , Neoplasias Experimentais , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Preparações de Ação Retardada , Feminino , Humanos , Hidrogéis , Masculino , Camundongos , Camundongos Nus , Paclitaxel/administração & dosagem , Processos FotoquímicosRESUMO
The normal anatomical structure of articular cartilage determines its limited ability to regenerate and repair. Once damaged, it is difficult to repair it by itself. How to realize the regeneration and repair of articular cartilage has always been a big problem for clinicians and researchers. Here, we conducted a comprehensive analysis of the physical properties and cytocompatibility of hydrogels, and evaluated their feasibility as cell carriers for Adipose-derived mesenchymal stem cell (ADSC) transplantation. Concentration-matched hydrogels were co-cultured with ADSCs to confirm ADSC growth in the hydrogel and provide data supporting in vivo experiments, which comprised the hydrogel/ADSCs, pure-hydrogel, defect-placement, and positive-control groups. Rat models of articular cartilage defect in the knee joint region was generated, and each treatment was administered on the knee joint cartilage area for each group; in the positive-control group, the joint cavity was surgically opened, without inducing a cartilage defect. The reparative effect of injectable glycol chitosan/dibenzaldehyde-terminated polyethylene glycol (GCS/DF-PEG) hydrogel on injured articular cartilage was evaluated by measuring gross scores and histological score of knee joint articular-cartilage injury in rats after 8 weeks. The 1.5% GCS/2% DF-PEG hydrogels degraded quickly in vitro. Then, We perform in vivo and in vitro experiments to evaluate the feasibility of this material for cartilage repair in vivo and in vitro.
RESUMO
Introduction: Water soluble polysaccharides are versatile structural materials that can be used for the design of biocompatible hydrogels and wet dressings in wound healing applications. Glycol chitosan (GC) is an example of a multifunctional water-soluble chitosan derivative that has inherent wound healing properties and reactive sites for chemical modification.Areas covered: United States (US) patent US2019202998A1 describes the preparation of a novel wound healing technology based on a three-dimensional (3D) crosslinked GC hydrogel (GCH) wet dressing, prepared via the synthesis of PEG1K-biscarboxylic acid-g-Glycol Chitosan-g-methacrylate using visible light induced photocrosslinking. The selected polymeric network enables the encapsulation of additional growth factors or bioactives on reactive sites. Wet dressings in US2019202998A1 were evaluated against a commercially available control for in vitro release, cytotoxicity, and in vivo wound healing ability in a preliminary mouse model, with the overall wound healing performance consistent with related GC-based hydrogels.Expert opinion: Comprehensive biocompatibility and antimicrobial testing of the hydrogel is not reported in US2019202998A1, and is recommended as further work to enable clinical applicability. The invention disclosed in US2019202998A1 can potentially be integrated with 3D bioprinting and sensor technology for the preparation of 'smart' hydrogel wound dressings, and is a potential area for future research.
Assuntos
Quitosana/farmacologia , Hidrogéis , Cicatrização/efeitos dos fármacos , Animais , Bioimpressão , Quitosana/química , Reagentes de Ligações Cruzadas/química , Modelos Animais de Doenças , Humanos , Luz , Camundongos , Patentes como Assunto , Polímeros/químicaRESUMO
Osteosarcoma (OSA) is a difficult cancer to treat due to its tendency for relapse and metastasis; advanced methods are therefore required for OSA treatment. In this study, we prepared a local drug-delivery system for OSA treatment based on doxorubicin·hydrochloride (DOX·HCl)/cisplatin (CP)-loaded visible light-cured glycol chitosan (GC) hydrogel/(2-hydroxypropyl)-beta-cyclodextrin (GDHCP), and compared its therapeutic efficiency with that of DOX·HCl- and CP-loaded GC hydrogels (GD and GHCP). Because of diffusion driven by concentration gradients in the swollen matrix, the three hydrogels showed sustained releases of DOX·HCl and CP over 7 days, along with initial 3-h bursts. Results of in vitro cell viability and in vivo animal testing revealed that GDHCP had a stronger anticancer effect than GD and GHCP even though there were no significant differences. Body weight measurement and histological evaluations demonstrated that the drug-loaded GC hydrogels had biocompatibility without cardiotoxicity or nephrotoxicity. These results suggested that GDHCP could be a good platform as a local drug-delivery system for clinical use in OSA treatment.