Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Abstract

Background Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer. Methods We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin. Conclusion DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.

Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

“…18 Specifically, 100 µL of pyrene solutions (1 × 10 −5 M in acetone) was transferred to a series of 10 mL volumetric flasks, then acetone was completely volatilized under a gentle stream of nitrogen. A series of aqueous copolymer solutions were added to the acetonefree pyrene flasks and made up to the mark with deionized water, yielding final pyrene and copolymer concentrations of 1 × 10 −7 M and 1 × 10 −5 to 0.1 mg/mL, respectively.…”

Dextran-b-poly(L-histidine) copolymer nanoparticles for pH-responsive drug delivery to tumor cells

“…Because dextran is biocompatible, biodegradable, and immunoneutral, it is extensively employed for modification of bioactive materials. 21,[25][26][27][28] Further, dextran has the potential to avoid unwanted protein or cellular absorption and to increase the blood circulation time, depending on molecular weight. [29][30][31] Dextran has also been used to deliver anticancer agents in systemic drug delivery systems.…”

“…21 The molecular weight, number-average molecular weight, and polydispersity index of dextran was 4,800, 4,370, and 1.098, respectively. Based on the molecular weight of dextran, the molecular weight 3199 ph-responsive drug delivery to tumor cells of PHS was evaluated by specific peaks of dextran and PHS from 1 H NMR spectroscopy.…”

“…21 Dextran 60 mg was dissolved in dimethylsulfoxide, and sodium cyanoborohydride (62.8 mg, 1 mM) was added. These mixtures were stirred for 24 hours at room temperature.…”

Oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer

“…Polymeric micelles with core-shell structure, formed by self-aggregation of amphiphilic graft or block copolymers, provide a significant advantage for delivering antitumor drugs to solid tumors. [18][19][20][21][22] Moreover, polymeric micelles are largely accumulated in tumor tissue via the passive "enhanced permeability and retention (EPR) effect." 23,24 Among the natural polysaccharides, the stearic acid-g-chitosan oligosaccharide (CSO-SA) micelles have been widely utilized as polymeric drug carriers due to their biocompatibility and biodegradability.…”