Schiff base-containing dextran nanogel as pH-sensitive drug delivery system of doxorubicin: Synthesis and characterization

Abstract

Stimuli-responsive hydrogels have been widely researched as carrier systems, due to their excellent biocompatibility and responsiveness to external physiologic environment factors. In this study, dextran-based nanogel with covalently conjugated doxorubicin (DOX) was developed via Schiff base formation using the inverse microemulsion technique. Since the Schiff base linkages are acid-sensitive, drug release profile of the DOX-loaded nanogel would be pH-dependent. In vitro drug release studies confirmed that DOX was released much faster under acidic condition (pH 2.0, 5.0) than that at pH 7.4. Approximately 66, 28, and 9% of drug was released in 72 h at pH 2.0, 5.0, and 7.4, respectively. Cell uptake by the human breast cancer cell (MCF-7) demonstrated that the DOX-loaded dextran nanogel could be internalized through endocytosis and distributed in endocytic compartments inside tumor cells. These results indicated that the Schiff base-containing nanogel can serve as a pH-sensitive drug delivery system. And the presence of multiple aldehyde groups on the nanogel are available for further conjugations of targeting ligands or imaging probes.

One‐Pot Synthesis of DOX@Covalent Organic Framework with Enhanced Chemotherapeutic Efficacy

“…DOX@COF was totally decomposedi nP BS by further decreasing the pH values or increasing the reaction times, leading to the complete release of DOX and revealing the pH-responsive properties. [38][39][40] The biocompatibility and cytotoxicity of COF,D OX and DOX@COF were investigated in vitro by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell assays.F igure S8 (Supporting Information) shows the in vitro cell viability curve of COF against L929 cells. After 24 hi ncubation, mosto ft he cells survived in the presence of pure COF at differentc oncentrations( 0-100 mgmL À1 ).…”

Application of Natural Biopolymersand its Derivatives as Nano -Drug Delivery Systems in Cancer Treatment

“…Numerous glycoconjugates have been derivatized by reactions, including esterification, etherification, and oxidation [58][59]. Many classes of dextran-based nanoparticulate systems for anticancer drug delivery have been reported in recent years [60][61][62][63].…”

Design and Applications of Tumor Microenvironment-Responsive Nanogels as Drug Carriers

“…In addition, the DOX with active amino groups in the molecules is often coupled to nanogels through Schiff base bond. The pH-sensitive drug-loaded nanogels were obtained through coupling hydroformylated dextran nanogels and DOX (Su et al, 2018). At pH 2.0, 5.0, and 7.4, the drug release amount within 72 h were about 66, 28, and 9%, while the physically loaded nanogels did not demonstrate acid-accelerated release behaviors.…”