Sadafara A. Pillai

Microstructure of copolymeric micelles modulated by ionic liquids: investigating the role of the anion and cation

Here we report comprehensive analysis of the influence of ionic liquids (ILs) on the physicochemical properties of an ethylene oxide–propylene oxide (EO–PO) star shaped block copolymer, Tetronic®1304 (total mol. wt = 10 500 and %PEO = 40%) hereafter referred to as T1304, by employing cloud point (CP), viscosity, dynamic light scattering (DLS), small-angle neutron scattering (SANS), high sensitivity differential scanning calorimetry (HSDSC) and fluorescence measurements and 1H NMR spectroscopy. 1-Alkyl-3-methylimidazolium based ILs varying in alkyl chain length (C4–C10) and anion, namely chloride, tetrafluoroborate, trifluoromethanesulfonate and hexafluorophosphate, were used. At lower concentrations, the ILs with different anions showed identical effects on the T1304 micelles but a significant change was noticed at higher concentrations. ILs with longer alkyl chains formed smaller mixed micelles while those with shorter chains remained in the bulk. Moreover, an increase in the alkyl chain length significantly increased the CP while the apparent hydrodynamic diameter (Dh) of the micelles decreased. In line with this, the variation in alkyl chain length has no significant effect on the CMT up to C8mimCl but decreases efficiently for C10mimCl. On the other hand, the variation in counter-ions seldom influenced the CP/Dh/CMT of the T1304 solutions at lower concentrations of the IL, but showed sufficient change at higher concentrations. The presence of NaCl suppressed the effect of the IL on the T1304 micelles. The microstructural changes as observed for the T1304 micelles in the presence of different ILs are explained using SANS data. Fluorescence studies with coumarin-481 as a probe showed shifts in the emission spectra and enhancement in the fluorescence decay, suggesting incorporation of the ILs in the micelles. The penetration of ILs with longer alkyl chains in the T1304 micelles was further confirmed using 1H NMR spectroscopy. The present study provides valuable information on tuning the solution behaviour of T1304 with ILs that may prove to be beneficial for different industrial applications.

A multitechnique approach on adsorption, self-assembly and quercetin solubilization by Tetronics® micelles in aqueous solutions modulated by glycine

Ethylene oxide-propylene oxide (EO-PO) block copolymer micelles are useful potential nanoreservoirs for the delivery of hydrophobic drugs. Considering that glycine is an excipient and can favorably affect the surface/micellar behavior and thus improve solubilization power/dispersion stability/wetting characteristics we have reported here studies on aqueous solution behavior of two commercially available branched block copolymers (Tetronics®) with differing hydrophobicities namely Tetronics® 1307 and 1304, hereafter referred as T1307 and T1304, in the presence of glycine. Steady state fluorescence studies using pyrene as a probe, equilibrium and dynamic surface tension measurements, wetting and dispersion stability studies of Teflon (polytetrafluoroethylene; PTFE) and solubilization studies of a hydrophobic antioxidant/anticancer drug quercetin (QN) have been examined. The cloud point (CP) and critical micelle temperature (CMT) decrease while micelle hydrodynamic size (Dh) increases with the addition of glycine as well as on loading of the drug in the micelles. Water penetration through packed PTFE powder and dynamic surface tension confirm the enhanced micellization process for aqueous Tetronic® solutions in presence of glycine and accordingly restricted diffusion for the surfactant molecules towards air-water and PTFE-water interface. The contact angles for Tetronic® solutions in presence of glycine indicate moderate decrease. The pressure-area curves of the copolymers in water and glycine solutions were also constructed. Surface and micellar properties of copolymers are markedly altered in the presence of glycine and can be tuned for use of these nanocarriers in delivery systems.

Glucose triggered enhanced solubilisation, release and cytotoxicity of poorly water soluble anti-cancer drugs fromT1307 micelles

Tetronic® 1307 (here after written as T1307) is a hydrophilic ethylene oxide-propylene oxide (EO-PO) star block copolymer with long EO chains (Total MW- 18000 and 70% EO). Although biocompatible, its use as a nanocarrier is restricted owing to its high critical micelle concentration (CMC) and temperature (CMT). We examined if the addition of glucose, a common pharmaceutical ingredient promotes micellization. Scattering and thermal studies show formation of stable unimodal micelles and cloud point (CP) decreased linearly. The solubilization of anticancer drugs viz. curcumin (CN) and quercetin (QN) demonstrates improved controlled release kinetics and cytotoxicity. On the whole, modulation in micellar behaviour by glucose opens enchanting possibility of using T1307 micelles as nanoreservoirs.

Microstructural micellar transition in bile salt–ionic liquid mixed systems in water: a DLS and SANS study

Due to the potential use and widespread applications of mixed micelles, herein we report the formation of rod-like micelles from the mixtures of a surface active ionic liquid (IL) and bile salt (BS). Mixed micelles of sodium deoxycholate (NaDC) and sodium cholate (NaC) with 1-decyl-3-methylimidazolium chloride (C10mim Cl) have been assessed by spectral and scattering techniques. These bile salts display electrostatic and hydrophobic interactions with the IL. The incorporation of bile salts in IL micelles leads to an increase in solution viscosity suggesting micellar growth and transitions. These observations are confirmed by dynamic light scattering (DLS) and further supported by small angle neutron scattering (SANS). The unusual viscosity behaviour is observed by altering the solution pH. NMR provided information on deeper penetration of NaDC molecules in IL micelles. Such a bile salt induced sphere-to-rod micellar transition further modulated by pH is of its first kind in an IL–bile salt mixed system.

A Comparative Study on Micellar and Solubilizing Behavior of Three EO-PO Based Star Block Copolymers Varying in Hydrophobicity and Their Application for the In Vitro Release of Anticancer Drugs

The temperature and pH dependent self-assembly of three star shaped ethylene oxide-propylene oxide (EO-PO) block copolymers (Tetronics® 304, 904 and 908) with widely different hydrophobicity was examined in aqueous solutions. Physico-chemical methods viz. viscosity, cloud point, solubilization along with thermal, scattering and spectral techniques shows strongly temperature and salt dependent solution behavior. T304 possessing low molecular weight did not form micelles; moderately hydrophilic T904 remained as micelles at ambient temperature and showed micellar growth while very hydrophilic T908 formed micelles at elevated temperatures. The surface activity/micellization/solubilization power was favored in the presence of salt. The copolymers turn more hydrophilic in acidic pH due to protonation of central ethylene diamine moiety that hinders micelle formation. The solubilization of a model insoluble azo dye 1-(o-Tolylazo)-2-naphthol (Orange OT) and hydrophobic drugs (quercetin and curcumin) for copolymer solutions in aqueous and salt solutions are also reported. Among the three copolymers, T904 showed maximum solubility of dye and drugs, hence the in vitro release of drugs from T904 micelles was estimated and the effect on cytotoxicity of loading the drugs in T904 micelles was compared with the cytotoxicity of free drugs on the CHO-K1 cells. The results from the present work provide a better insight in selection of Tetronics® for their application in different therapeutic applications.