Amphiphilic diblock copolymers based on poly(2‐ethyl‐2‐oxazoline) and poly(4‐substituted‐ε‐caprolactone): Synthesis, characterization, and cellular uptake

Abstract

Amphiphilic diblock copolymers with various block compositions were synthesized on poly(2‐ethyl‐2‐oxazoline) (PEtOz) as a hydrophilic block and poly(4‐methyl‐ε‐caprolactone) (PMCL) or poly(4‐phenyl‐ε‐caprolactone) (PBCL) as a hydrophobic block. These PEtOz‐b‐PMCL and PEtOz‐b‐PBCL copolymers consisting of soft domains of amorphous PEtOz and PM(B)CL had no melting endothermal peaks but displayed Tg. The lower critical solution temperature (LCST) values for the PEtOz‐b‐PMCL, and the PEtOz‐b‐PBCL aqueous solution were observed to shift to lower temperature than PEtOz homopolymers. Their aqueous solutions were characterized using fluorescence techniques and dynamic light scattering (DLS). The block copolymers formed micelles with critical micelle concentrations (CMCs) in the range 0.6–11.1 mg L−1 in an aqueous phase. As the length of the hydrophobic PMCL or PBCL blocks elongated, lower CMC values were generated. The mean diameters of the micelles were between 127 and 318 nm, with PDI in the range of 0.06–0.21, suggesting nearly monodisperse size distributions. The drug entrapment efficiency and drug‐loading content of micelles depend on block polymer compositions. In vitro cell viability assay showed that PEtOz‐b‐PMCL has low cytotoxicity. Doxorubicin hydrochloride (DOX)‐loaded micelles facilitated human cervical cancer (HeLa) cell uptake of DOX; uptake was completed within 2 h, and DOX was able to reach intracellular compartments and enter the nuclei by endocytosis. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2769–2781

Recent developments in micellar drug carriers featuring substituted poly(ε-caprolactone)s

“…Thermoresponsive block copolymers comprised of poly(2ethyl-2-oxazoline) and methyl-(M2) or phenyl-(M3) substituted caprolactone, were investigated by Peng et al (Scheme 18(a)). 70 Temperature-responsive polymers like these are soluble in water below their lower critical solution temperature (LCST), but are insoluble once the solution is heated above the LCST. Incorporation of the substituted caprolactone in the hydrophobic block reduced the LCST as low as 38 °C, compared to the poly(2-ethyl-2-oxazoline) homopolymer with LCST around 90 °C.…”

Interaction Pathways between Plasma Membrane and Block Copolymer Micelles

“…Many experiments have been conducted to investigate the drug-delivery performance of BCMs. Block copolymers with various physical and chemistry properties were used to prepare BCMs with desirable cellular uptake performance and low cytotoxicity. − Several parameters of polymers and micelles (e.g., degree of polymerization and hydrophobic/hydrophilic volume fraction) strongly affect the cellular internalization results. − However, due to the limitations of current experimental techniques, little is known about BCM–membrane interaction pathways. For example, it is not known how the BCM penetrates the membrane and enters the cell.…”

Thermosensitive t -PLA-b -PNIPAAm tri-armed star block copolymer nanoscale micelles for camptothecin drug release

“…Since the micellization behavior of block copolymers in aqueous solution was found by Tuzar and Kratochvíl in 1976, block copolymers, especially amphiphilic block copolymers have widely been studied. This copolymer generally contains hydrophilic and hydrophobic segments, and hence can self‐assemble into core‐shell nanoscale micelles in aqueous solution by hydrophobic, electrostatic, metal complexation, or hydrogen bonding interactions . The lipophilic core can effectively dissolve water‐insoluble substances, and the hydrophilic shell can retain the micelles stable in aqueous solution.…”