Synthesis of amphiphilic [PEO(PCL)2] triarm star-shaped block copolymers: a promising system for in cell delivery

Abstract

The paper reports on a simple method of synthesizing [PEO(PCL)(2)] triarm star-shaped copolymers by a combination of Michael-addition type reaction and ring-opening polymerization. A Michael-addition reaction yielded a PEO end-capped by two hydroxyl groups-a [PEO(OH)(2)] macroinitiator-which was used for sequential building of PCL blocks. The macroinitiator and copolymers were analyzed by FTIR, (1)H NMR spectroscopy and SEC. The self-assembly behavior of the copolymers in aqueous media was studied by UV-Vis spectroscopy. The size and morphology of the obtained micelles were determined by TEM. None of the polymers had cytotoxic effects in vitro. Cellular uptake studies showed the accumulation of neutral red loaded micelles in the perinuclear area of human hepatocellular carcinoma cells revealing a cellular uptake associated with macropinocytosis and caveolae mediated endocytosis. The accumulation had a sustained effect over 3 days pointing at the potential application of the copolymers micelles as a drug delivery system.

Towards the development of polycaprolactone based amphiphilic block copolymers: molecular design, self-assembly and biomedical applications

“…[50] The degradation study showed that 3-arm star-shaped PCL/PEG block copolymers with shorter PCL block length degraded faster. The coreshell micelle sizes fluctuated during the initial degradation period and then increased slightly before finally dropping off.…”

“…50] With the fast evolution of polymerization techniques, several synthetic strategies have been reported for the effective synthesis of PCL based star-The obtained 3-arm star-shaped PCL/PEG block copolymers can form micelles by self-assembly without contact with any organic solvent. The micelle properties as investigated by size distribution, zeta potential, and TEM visualization of the micelles indicated that the micelles are homogeneous and stable.…”

Nanomicelles based on X-shaped four-armed peglyated distearylglycerol as long circulating system for doxorubicin delivery

“…Recently Y-shaped three-armed block copolymers with one hydrophilic head and two hydrophobic tails have been receiving a great attention (Li et al, 2013;Wang et al, 2012aWang et al, , 2010Petrova et al, 2012;Maglio et al, 2011). Compared with their linear counterparts, triarm copolymers are characterized with smaller hydrodynamic volume and radius of gyration, and lower melt and solution viscosities (Lapienis, 2009;Sanda et al, 2002;Lele and Leroux, 2002;Joziass et al, 2000).…”

Supramolecular self-assembly of novel thermo-responsive double-hydrophilic and hydrophobic Y-shaped [MPEO-b-PEtOx-b-(PCL)2] terpolymers

“…Star-shaped block copolymers consisting of at least three linear polymeric arms with a radial arrangement around a central molecular fragment (core) 8,9 are usually prepared by the "arm-rst" or "core-rst" methods. The "arm-rst" approach involves the construction of polymer arms on a macroinitiator that contains a precise number of reactive sites.…”

“…13,14 These micellar systems are of great interest for medical uses such as the construction of micellar drug delivery systems. 9,[15][16][17][18][19] Signicant differences in the physicochemical properties of star-shaped copolymers compared with their linear analogues can be observed, such as smaller hydrodynamic volume and, radius of gyration and low melt and solution viscosities, which are benecial to drug loading and delivery. [20][21][22][23][24] It has been shown that linear amphiphilic copolymers have limited applications in drug delivery because they suffer from an initial burst release effect.…”