Morphology, gelation and cytotoxicity evaluation of D-α-Tocopheryl polyethylene glycol succinate (TPGS) – Tetronic mixed micelles
Puig-Rigall, Joan
Blanco-Prieto, María J. / Radulescu, Aurel / Dreiss, Cécile A. (Corresponding author) / González-Gaitano, Gustavo (Corresponding author)
Heinz Maier-Leibnitz Zentrum; MLZ
Neutronenstreuung ; Neutronenstreuung; JCNS-1
JCNS-FRM-II; JCNS-FRM-II
Journal of colloid and interface science, 582 (2021) Part A, S. 353 - 363
Amsterdam [u.a.] Elsevier 2021
10.1016/j.jcis.2020.08.004
Journal Article
FRM II / MLZ
Jülich Centre for Neutron Research (JCNS)
Published on 2020-08-03. Available in OpenAccess from 2022-08-03.
Published on 2020-08-03. Available in OpenAccess from 2022-08-03.
Please use the identifier: http://dx.doi.org/10.1016/j.jcis.2020.08.004 in citations.
Please use the identifier: http://hdl.handle.net/2128/25649 in citations.
HypothesisThe combination of polymeric surfactants into mixed micelles is expected to improve properties relevant to their use in drug delivery, such as micellar size, gelation, and toxicity. We investigated synergistic effects in mixtures of D-α-Tocopheryl polyethylene glycol succinate (TPGS), an FDA-approved PEGylated derivative of vitamin E, and Tetronic surfactants, pH-responsive and thermogelling polyethylene oxide (PEO)-polypropylene oxide (PPO) 4-arm block copolymers. We hypothesized that mixed micelles would form under specific conditions and provide a handle to tune formulation characteristics.ExperimentsWe examined the morphology of the self-assembled structures in mixtures of TPGS with two Tetronic: T1107 and T908, using a combination of dynamic light scattering (DLS), small-angle neutron scattering (SANS), NMR spectroscopy (NOESY and diffusion NMR) and oscillatory rheology, over a range of compositions, temperatures and pH. Cell viability was assessed in NIH/3T3 fibroblasts.FindingsThe combination of TPGS with either of the two Tetronic produces spherical core-shell micelles that comprise both surfactants in their structure (mixed micelles). T1107 unimers incorporate into TPGS aggregates below the critical micelle temperature of the poloxamine, while mixed micelles only form under limited conditions with T908. At high concentration/temperature, small proportions of TPGS extend the gel phase, more markedly with T1107, with similar elastic moduli (30–50 kPa) and a BCC crystalline structure. Cell viability of NIH/3T3 fibroblasts grown in the hydrogels increases significantly when the poloxamine gels are doped with TPGS, making the combination of poloxamines and TPGS a promising platform for drug delivery.