Abstract
Doxorubicin-pluronic F68 conjugate (DOX-P) was synthesized and its structure was confirmed by FTIR and 1H-NMR spectra. Using human erythroleukemic cancer cells as model, DOX-P application in chemotherapy was further investigated. Differential scanning calorimetry analysis was applied to compare the fusion and crystallization characterization between pluronic F68 and DOX-P. Morphology and size assessment were measured using a transmission electron microscopy (TEM) to confirm the capability of forming micelles of DOX-P. Tumor cell lines K562 and K562/AO2 were used to investigate the effect of DOX-P on tumor cell resistance. The Tm and Tc of DOX-P were lower than pluronic F68 resulted from the connection of DOX to pluronic F68. Morphology images confirmed the existence of DOX-P micelles, with an average size of about 20 nm. Drug release profile showed that the DOX-P conjugate maintained a sustained DOX release. From cell experiment in vitro, DOX-P micelles could circumvent the DOX resistance of K562/AO2 cells. With advantages of EPR effect and reducing tumor resistance, DOX-P micelles might develop as new tumor targeted delivery system for chemotherapy.
Highlights
Polymer-based drug delivery systems emerged from the laboratory bench in the 1990s as a promising therapeutic strategy for the treatment of cancer and other devastating diseases [1,2,3]
These peaks were absent in the 1H-NMR spectra of DOX conjugated pluronic F68, and a series of new peaks appeared due to the introduction of DOX moieties into the copolymers
The structures of CT-Pluronic F68 and Doxorubicin-pluronic F68 conjugate (DOX-P) were confirmed by FTIR and 1H-NMR spectra
Summary
Polymer-based drug delivery systems emerged from the laboratory bench in the 1990s as a promising therapeutic strategy for the treatment of cancer and other devastating diseases [1,2,3]. One promising example of such polymer nanomaterials is presented by a class of Pluronic block copolymers ( known under non-proprietary name poloxamers) [2,4,5,6]. These block copolymers consist of hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) blocks arranged in A-B-A tri-block structure: PEO-PPO-PEO (Figure 1). Due to their amphiphilic character these copolymers display surfactant properties including ability to interact with hydrophobic surfaces and biological membranes. The diameters of Pluronic micelles usually vary from 10nm to 100nm
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