Joan Puig-Rigall1, María J Blanco-Prieto2, Aurel Radulescu3, Cécile A Dreiss4, Gustavo González-Gaitano5. 1. Departamento de Química, Universidad de Navarra, 31080 Pamplona, Spain. 2. Departamento de Tecnología y Química Farmacéutica, Universidad de Navarra, 31080 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra, IdiSNA, Irunlarrea 3, 31008 Pamplona, Spain. Electronic address: mjblanco@unav.es. 3. Jülich Center for Neutron Science, JCNS at Heinz Maier-Leibnitz Zentrum MLZ, Forschungszentrum Jülich GmbH, Lichtenbergstraße 1, 85747 Garching, Germany. 4. Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: cecile.dreiss@kcl.ac.uk. 5. Departamento de Química, Universidad de Navarra, 31080 Pamplona, Spain. Electronic address: gaitano@unav.es.
Abstract
HYPOTHESIS: The 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. EXPERIMENTS: We 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. FINDINGS: The 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.
HYPOTHESIS: The 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. EXPERIMENTS: We 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. FINDINGS: The 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.
Authors: Mohammed W Al-Rabia; Mohamed A Alfaleh; Hani Z Asfour; Waleed S Alharbi; Mohamed A El-Moselhy; Nabil A Alhakamy; Usama A Fahmy; Osama A A Ahmed; Omar Fahmy; Omar M Rashad; Abdulmohsin J Alamoudi; Ashraf B Abdel-Naim Journal: Antioxidants (Basel) Date: 2022-07-30
Authors: Nabil A Alhakamy; Osama A Ahmed; Usama A Fahmy; Hani Z Asfour; Adel F Alghaith; Wael A Mahdi; Sultan Alshehri; Shadab Md Journal: Front Pharmacol Date: 2021-07-16 Impact factor: 5.810