Role of Unimers to Polymersomes Transition in Pluronic Blends for Controlled and Designated Drug Conveyance

resumo

This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (eta(rel)) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of <= 5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (Delta G degrees), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.

palavras-chave

BLOCK-COPOLYMER; TRIBLOCK COPOLYMER; INDUCED MICELLIZATION; AQUEOUS-SOLUTIONS; LIGHT-SCATTERING; PROPYLENE-OXIDE; ETHYLENE-OXIDE; MICELLES; DELIVERY; TEMPERATURE

categoria

Chemistry

autores

Patel, D; Tripathi, N; Vaswani, P; Pérez-Sánchez, G; Bhatia, D; Kuperka, K; Coutinho, JAP; Bahadur, P

Grupos

G4 - Materiais Renováveis e Economia Circular
G6 - Materiais Virtuais e Inteligência Artificial

Projectos

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

agradecimentos

The authors acknowledge the Sardar Vallabhbhai National Institute of Technology (SVNIT), Gujarat, India, for providing instrumentation facilities. The authors also acknowledge the scattering experiments support from the Solid State Physics Division, Bhabha Atomic Research Centre (BARC), Mumbai, India. The authors also acknowledge Arash Elahi (Department of Chemical Engineering at the University of Illinois at Chicago, USA) for kindly providing the MD computer simulation input files for the Pluronic molecules used in this work. The computational part of this work was funded by the CICECO-Aveiro Institute of Materials under the projects UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020 and financed by national funds through the FCT/MEC (PIDDAC. German Perez-Sanchez acknowledges the national funds (OE), ref DL 57/2016/CP1482/CT004 and DOI: 10.54499/DL57/2016/CP1482/CT0043 through FCT-Fundacao para a Ciencia e a Tecnologia, I.P., in the scope of the framework contract foreseen in numbers 4, 5, and 6 of the articles 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Simulations were performed at the OBLIVION Supercomputer managed by the HPC Centre of the University of Evora and acquired under the "Enabling Green E-science for the SKA Research Infrastructure (ENGAGE SKA)", reference POCI-01-0145-FEDER-022217, funded by COMPETE 2020 and the Foundation for Science and Technology (FCT), Portugal. No specific grants were received from any funding agencies in the public, commercial, or not-for-profit sectors for the experiments. Simulations were financed by the FCT program "Concurso de Projetos de Computacao Avancada -3ay Edicao '' with the project reference CPCA/A2/15575/2022.