•Glucose promotes micellization of an amphiphilic copolymer Tetronic®1307 in water.•The CMC, CMT and CP obtained from surface tension and HSDSC decreased.•The Dh (from DLS) and Rc, Rhs and Nagg(from ...SANS) increased.•The solubilisation, release and cytotoxicity of drugs improved.•The presence of glucose dehydrates corona inducing hydrophobicity in 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.
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.
A comparative analysis of the micellar and solubilizing properties of two polyethylene glycol (PEG)-based amphiphilic biocompatible excipients: Gelucire® 48/16 (Ge 48/16) and Tetronics® 1304 (T1304), ...in the presence and absence of salt, was conducted. As there is a dearth of research in this area, the study aims to shed light on the behavior of these two nonionic surfactants and their potential as nanocarriers for solubilizing pharmaceuticals. Various techniques such as cloud point (CP), dynamic light scattering (DLS), small-angle neutron scattering (SANS), Fourier transform infrared spectroscopy (FT-IR), UV spectrophotometry, and high-performance liquid chromatography (HPLC) were employed. The solubility of quercetin (QCT), a flavonoid with anti-inflammatory, antioxidant, and anti-cancer properties, was evaluated and the interaction between QCT and the micellar system was examined. The analysis revealed the occurrence of strong interactions between QCT and surfactant molecules, resulting in enhanced solubility. It was observed that the micellar size and solubilizing ability were significantly improved in the presence of salt, while the CP decreased. Ge 48/16 exhibited superior performance, with a remarkable increase in the solubility of QCT in the presence of salt, suggesting its potential as an effective nanocarrier for a range of pharmaceutics, and yielding better therapeutic outcomes.
Comparative analysis of PEG-based excipients Gelucire® 48/16 and Tetronics® 1304, for micellar and solubilizing properties.
Abstract
This manuscript explains the effect of biologically important additives on the micellar behavior of an ethylene oxide‐propylene oxide (PEO
101
‐PPO
56
‐PEO
101
) based linear block ...copolymer, Poloxamer 407.The effect of common pharmaceutical excipients and three vital amino acids viz. alanine, glycine, and lysine (Ala, Gly, and Lys) is examined with the help of cloud point (CP), dynamic light scattering (DLS), and small angle neutron scattering (SANS) techniques. The drug solubilization ability for the copolymer was checked for two model drugs Quercetin (QCT) and Ibuprofen (IBU) with the help of high‐performance liquid chromatography (HPLC) in the presence/absence of additives such as Ala, Gly, and Lys. The observed results reveal that higher amino acid concentrations, favor the solubilization of drug which can potentially benefit the use of these biocompatible copolymers in pharmaceutical and biopharma industries.
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Glycine promotes micellization and micellar growth in aqueous Tetronic® solutions.The data on CMC, CMT, CP, viscosity and micelle size are presented.Changes in pH also alters ...aggregation number and micellar size.The results provide useful insight on microstructural changes in Tetronic® micelles by glycine under different solution conditions.
We report here calorimetric and scattering studies on two pharmaceutically important, commercially available nonlinear ethylene oxide-propylene oxide (EO-PO) octablock copolymers, Tetronic®1304 (T1304) and Tetronic®1307 (T1307) (with almost same molecular weight of polypropylene oxide (PPO) and varying % polyethylene oxide (PEO)), in the presence of amino acid, glycine. Added glycine in aqueous solution exhibits water structure-making behaviour and thus induces micellization by altering the polarity of water. Consequently, lowering of cloud point (CP), critical micelle concentration (CMC) and critical micellization temperature (CMT) of copolymer solutions with a corresponding change in solution viscosity is observed. The microstructural changes as evidenced by small angle neutron scattering (SANS) and dynamic light scattering (DLS), for Tetronic® micelles strongly depend upon their hydrophobicity, glycine concentration, temperature and pH of solution. In the case of T1304 with lesser % PEO, behaves as moderately hydrophobic and displays pronounced micellar growth as a function of glycine concentration and at alkaline pH. Such a transition in micelle size with pH is explained in terms of sticking parameter. T1307 with higher % PEO, is highly hydrophilic and does not show micellar growth even at higher concentration of glycine/alkaline pH. The measured CMTs obtained from high sensitivity differential scanning calorimetry (HSDSC) and calculated thermodynamic parameters clearly signify glycine induced micellization. The results were elucidated in terms of structure making properties of glycine. The information attained from this contribution will be potentially commodious for an efficient exploitation of Tetronic® micelles in diverse pharmaceutical applications utilizing a common excipient, glycine.
To have a better insight into the influence of 2,2,2- trifluoroethanol (TFE) and ethanol (EtOH) on self-assembly of commercially available ethylene oxide- propylene oxide (EO-PO) octa-block ...copolymers, Tetronics® 1304 and 1307 in aqueous solutions, here we report results based on small angle neutron scattering (SANS) and fluorescence techniques. The critical micelle temperature (CMT) as determined by fluorescence for both the copolymers, suggested a significant decrease in values in the presence of TFE, which is in contrast to the observed increase in CMT in the presence of EtOH. For T1304 aqueous solutions, micellar growth is observed either as a function of TFE concentration or with an increase in the temperature for a fixed concentration of TFE. Conversely, for T1307 solutions, with a very hydrophilic character, presence of TFE had least effect on the micellar dimensions, though compact micelles with reduced polydispersity are witnessed for otherwise polydispersed solutions as evidenced by SANS. In short, the addition of halogenated alkanol, TFE had a completely opposite effect on the copolymer micelles than its nonhalogenated analogue, EtOH. The present study based on copolymeric micelles (biomimetic aggregates) may help in understanding influence of these co-solvents even on protein folding and other complex biological aggregates.
•Effect of cosolvents TFE/EtOH & temperature was checked on Tetronics® micelles•Fluorescence study revealed that TFE decreases CMT while EtOH increases it•SANS revealed occurrence of spherical core-shell micelles•Increase in concentration of TFE/temperature promoted micellization•EtOH plays a disruptive role and leads to micellar breakdown
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•Self-assembly of two biocompatible amphiphilic star block copolymers is examined.•Micellization/adsorption characteristics are modulated by the presence of glycine.•CMT, π-A ...isotherms, micelle size and quercetin solubilisation are reported.•Glycine markedly enhances solubility/stability of the drug in micelles.
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.
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The influence of glycol additives on the aqueous solution behaviour of T1304 was examined.Hydrophobic glycol additives form mixed micelle and decrease CP/CMT but increase micelle ...size/relative viscosity/Nagg.Hydrophilic glycol additives act like co-solvents and favor demicellization, decrease Nagg and increase CP/CMT.The information is highly commodious for an efficient exploitation of block copolymers using glycol additives.
The influence of different glycol additives on the phase behaviour and micellar characteristics of a moderately hydrophobic ethylene oxide-propylene oxide(EO-PO) star block copolymer Tetronic®1304 (hereafter written as T1304) has been investigated by cloud point (CP), viscosity, high sensitivity differential scanning calorimetry (HSDSC), dynamic light scattering (DLS) and small angle neutron scattering (SANS). Glycol additives are commonly used in several industrial and pharmaceutical applications in the presence of these biocompatible, linear and branched EO-PO block copolymers functioning as dispersants, emulsifiers, detergents, defoaming agents and vehicles in pharmaceutical applications. Hence, it is essential to understand the behavior of star block copolymers in their presence (glycol additives) to optimize the performance for applications in diverse areas.
In the case of short chain glycols/ethers/cyclic ethers an increase in CP, critical micelle temperature (CMT), hydrodynamic diameter (Dh) has been observed while aggregation number (Nagg) and relative viscosity decreases indicating demicellization. On the other hand, the long chain glycol ethers/aryl ethers/esters promote micellization with an increase in Nagg, micelle size, relative viscosity and decreased CMT. The influence on the micellar characteristics of T1304 is mainly dominated by the hydrophobicity and locus of solubilization of the glycol additives. The morphology of the star block copolymers can thus be customized using different glycol additives for particular applications. The information from this work will be highly lucrative for the industrial and therapeutic applications of star block copolymers using commonly used glycols to optimize their performance.
Here we report, a comparative study on the micellization and phase behavior of two commercially available ethylene oxide – propylene oxide (EO-PO) octablock copolymers, Tetronics® 1304 and 1307 ...(hereafter written as T1304 and T1307), in the presence of 2,2,2‑trifluoroethanol (TFE) and ethanol (EtOH) using cloud point (CP), dynamic light scattering (DLS), high sensitivity differential scanning calorimetry (HSDSC), relative viscosity and Langmuir film balance. These copolymers fabricated with almost the same PO block length vary in their EO chain lengths and hence display different characteristics. T1304 shows a more hydrophobic character and forms micelles at ambient temperature while T1307, due to longer EO chain length, exhibits high hydrophilicity and faces difficulty in forming micelles which results into high polydispersity in the aqueous system. In the presence of co-solvents TFE and EtOH, however a more interesting behavior is noted. T1304, as evident from DLS and viscosity measurements, displays micellar growth in the presence of TFE, while the presence of EtOH induces micellar breakdown. Though, in case of T1307, presence of TFE improves micellization and a single micellar peak becomes evident in the DLS stacks, no micellar growth can be noticed both through DLS and relative viscosity, which is possibly due to its highly hydrophilic character. Likewise, presence of TFE depresses the CMT in both the copolymers while EtOH increases it. A similar trend is also justified by π-A isotherms form Langmuir monolayers.
•Micellar behavior of amphiphilc EO-PO starblock copolymers examined in the presence of cosolvents TFE and EtOH.•Calorimetric and light scattering data and pressure-area isotherms reveal the contrast effect cosolvents.•TFE favored micellization and micellar growth.•The effect to two alcohols on colloid-chemical behavior of copolymers is discussed.
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 1 H NMR spectroscopy. 1-Alkyl-3-methylimidazolium based ILs varying in alkyl chain length (C 4 –C 10 ) 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 ( D h ) of the micelles decreased. In line with this, the variation in alkyl chain length has no significant effect on the CMT up to C 8 mimCl but decreases efficiently for C 10 mimCl. On the other hand, the variation in counter-ions seldom influenced the CP/ D h /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 1 H 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.
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