Mixed Micellar System Research Articles

Interactions in mixed micellar systems comprising chiral cationic amino acid based and conventional anionic surfactants

The formation of mixed micelle in water between a chiral cationic amino acid based surfactant, l-alaninehydrochloride dodecylester (l-ADDE), and conventional anionic surfactants (AS), sodium decyl sulfate (SDS), sodium dodecyl sulfate (SDDS) and sodium dodecylbenzene sulfonate (SDBS), has been investigated by conductivity, density and dynamic light scattering (DLS) measurements at 25 °C. The critical micelle concentrations (CMC), degree of counterion dissociation (α) and standard Gibbs energy of micellization (ΔGmic°) have been determined for both pure and mixed systems, and the results have been compared with each other. Physicochemical parameters included the critical micelle concentration of ideal mixtures (CMCideal), the mole fraction of l-ADDE in ideal (XL−ADDEideal) and real mixed micelles (XL−ADDE), and interaction parameter (β) have been calculated by theoretical models to reveal the properties of mixed micelles. l-ADDE/SDS mixed system exhibited behavior changing from synergistic to antagonistic interactions with increasing l-ADDE concentration, whereas a reverse case was observed in l-ADDE/SDBS mixed system, i.e., from antagonistic to synergistic interactions. l-ADDE/SDDS mixed system showed antagonistic interactions over all the mole fraction range studied. The change of the apparent molal volume upon micellization (∆Vφmic) values determined from density measurements revealed that mixed micelles packed more tightly than their corresponding pure micelles. In addition, the sizes of the aggregates in binary mixed systems were found to be larger than those of the pure ones indicating the transformation from the small micelles to large aggregated structures. The increment in size of aggregates may be suggested with the vesicular structures.

Effect of Ionic Liquids as Cosurfactants on Photoinduced Electron Transfer in Tetronic Micelles.

This study investigates the role of varying alkyl chain lengths of a series of surface-active 1-alkyl-3-methylimidazolium tetrafluoroborate ([C nMIm][BF4], n = 4, 6, and 10) ionic liquids (ILs) as cosurfactants in modifying the micellar characteristics of a tetronic star-block copolymer, T1304, and the consequent effects on bimolecular photoinduced electron transfer (PET) reactions carried out in these T1304-IL mixed micellar systems. Using coumarin 153 as the probe dye and following ground-state absorption, steady-state fluorescence, and time-resolved emission measurements, the micropolarity, microviscosity, and solvent relaxation dynamics in the micellar palisade layer have been revealed both in pure T1304 and in T1304-IL systems. With increasing alkyl chain length of the ILs, the palisade layer of the micelles gradually becomes more polar and less viscous, suggesting better incorporation of the longer alkyl chain length ILs as cosurfactants into the T1304 micelles. The bimolecular PET reactions, involving 7-aminocoumarins as acceptors and N, N-dimethylaniline as the donor, are considerably modulated in T1304 micelles by the presence of the ILs, the effect being more prominent for ILs with longer alkyl chain lengths. In all of the micellar systems, correlations of the electron transfer (ET) kinetics with the reaction exergonicity (-Δ G0) show clear Marcus inversion (MI) behavior where onsets of MI invariably appear at significantly lower exergonicities, suggesting the involvement of a two-dimensional ET mechanism. Interestingly, the Marcus correlations display significant variations, namely, enhanced reaction rates and gradual shift in the onset of MI toward higher exergonicity, as longer alkyl chain length ILs are sequentially introduced as cosurfactants. From the observed results, it is convincingly realized that 1-alkyl-3-methylimidazolium-based ILs can be used satisfactorily as cosurfactants in tetronic star-block copolymer solutions to modulate PET reactions very significantly for their better utilizations in suitable applied areas.

Preparation of ginsenoside compound-K mixed micelles with improved retention and antitumor efficacy.

IntroductionGinsenoside compound K (CK) has effects on cell-cycle regulation, tumor growth inhibition, and apoptosis induction. However, it has limited applications in clinical settings because of its low solubility and poor absorption.MethodsTo overcome these limitations, we aimed to develop a mixed micellar system composed of phosphatidylcholine (PC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine polyethylene glycol 2000 (DSPE PEG 2000; DP). CK encapsulated in PC/DP mixed micelles had enhanced solubility, permeability, and retention effects.ResultsCompared to free CK, the CK PC/DP micellar system exhibited improved anticancer effects in vitro, including cell-cycle arrest, apoptosis, and anti-invasion in human lung carcinoma A549 cells. The significant proapoptotic effect was reflected by increased chromosomal condensation, annexin V/propidium iodide staining, and related protein expression. In vitro cellular uptake and optical mouse imaging in vivo suggested that the improved antitumor effect was caused primarily by enhanced uptake and tumor targeting. Furthermore, an in vivo antitumor efficacy study indicated that the CK mixed micelles significantly inhibited tumor growth, thereby decreasing tumor volume at the end of the experiment as compared with that in the control mice. Histological analysis confirmed the antitumor effect with low toxicity.ConclusionThe PC/DP micellar system was an effective drug delivery system for CK in tumor therapy.

Mixed micellar system stabilized with saponins for oral delivery of vitamin K.

Poorly soluble vitamin K cannot be absorbed by patients suffering from cholestasis due to extremely low level of bile salts in the intestine. A formulation of vitamin K including glycocholic acid (i.e. Konakion® MM), does not increase bioavailability because it is unstable due to protonation of glycocholic acid at gastric pH. To develop a stable formulation, saponins were introduced as neutral surfactants to (partly) replace glycocholic acid. Experimental design was made to investigate the effect of the composition on particle size at neutral pH and upon acidification at pH 1.5. Two formulations that were within the optimized composition window were loaded with vitamin K and those showed superior stability at low pH as compared to Konakion® MM: sizes were between 43 and 46 nm at pH 7.3 and between 46 and 58 nm after 1 h incubation at pH 1.5, respectively, but large aggregates were formed at pH 1.5 in presence of Konakion® MM. Micelles were cytocompatible with Caco-2 cells at concentration of surfactants (saponins and glycocholic acid) up to 0.15 mg/ml. Uptake of vitamin K by Caco-2 cells was 4.2-4.9 nmol/mg protein for saponins-containing formulations and 7.1 nmol/mg protein for Konakion® MM. This, together with the superior stability at low pH, makes saponins-containing mixed micelles promising oral formulations for vitamin K.

A Global Scenario on the Dynamics of Excited State Proton Transfer of Pyranine in the Mixed Micellar Assemblies: Role of Water Accessibility in the Probe Location+

AbstractExcited state proton transfer (ESPT) dynamics of pyranine (HPTS) is explored in mixed micellar aggregate of pluronic F127 micelles and Na‐dodecyl sulfate (SDS) employing steady state and time resolved fluorescence. HPTS shows two proton transfer (PT) time constants in both F127 and F127‐SDS micelles. The slow ∼1.05 ns component in F127 micelles is attributed to PT occurring in the corona phase; whereas, the bulk water‐like variant (∼160 ps) arises from the probe in water exposed micellar periphery. Addition of SDS upto some low concentration in F127 produces mixed micelles due to SDS‐monomer incorporation. The slower ESPT time constant becomes ∼670 ps in the mixed micellar system (∼1.5 times faster than in neat), whereas, the faster one gets ∼140 ps. It is known that association of SDS in F127 micelles enhances water penetration in the corona region, thus this increased hydration speeds up the ESPT. The chosen photoacid, in principle, can anticipate changes in the microenvironment of the mixed micelles via modulation of its ESPT. In spite of similar hydration enhancements in both cationic and anionic mixed micelles, it is observed that the modification pattern of the ESPT in mixed anionic is opposite to that of mixed cationic. A rationale of such contrasting ESPT responses in these differently charged composites is presented. In addition to copolymeric micelles, some mixed systems formed with other nonionic‐ionic combinations are also explored to cast a more generalized picture

Self-assembled and pH-sensitive mixed micelles as an intracellular doxorubicin delivery system

Nanocarrier-based drug delivery systems have been explored extensively in cancer therapy. Among the vast number of different nanocarrier systems applied to deliver chemotherapeutics to cancer tumor, intelligent systems which deliver drug to various sites in the body have attracted considerable attentions. Finding a specific stimulant that triggers the carrier to release its payload in the target tissue is a key parameter for efficacy of delivery systems. Acidic pH of cancer tumor helps a pH-sensitive carrier to release drug at the tumor site. In this study, a pH-sensitive mixed micellar system was developed using Dextran-Stearic Acid (Dex-SA) and Dextran-Histidine (Dex-His) conjugated polymers to deliver doxorubicin (DOX) to cancer cells. Drug release from this micellar system showed higher release rate at acidic pH than that of in neutral environment, where the release was 56 and 76% at pH 7.4 and acidic pH, respectively. Finally, the in vitro cytotoxicity and cell uptake of DOX-loaded micelles and free DOX on U87 MG cell line showed that micellar systems had more anti-proliferation effect and uptake compared to free drug.

Binary mixed micellar systems of PEO-PPO-PEO block copolymers for lamotrigine solubilization: a comparative study with hydrophobic and hydrophilic copolymer

Polyethyelene oxide-polypropylene oxide-polyethyelene oxide, PEO-PPO-PEO triblock copolymers, Pluronics® are considered to be the best nanocarrier for hydrophobic substances on account of their wonderful solubilization power over other ionic and non-ionic surfactants. In the present manuscript, the Pluronic® binary mixtures (two systems, F127/P123 and F127/L35) as micellar nanocarriers for solubilization of lamotrigine (LTG) drug were investigated through UV-Visible spectroscopy, dynamic light scattering (DLS) and small angle neutron scattering (SANS) analysis. Both the binary systems form stable mixed micelles had low CMC in water. The CMC of binary systems, F127/P123 was located in the middle of the CMC of each copolymer, but it was slightly increased in the F127/L35 mixed systems. Results of DLS and SANS data were proven the spherical shape of micelles for both the binary systems with less than 30-nm diameter in sizes. Not much but mixed micelle became slightly larger after solubilizing of LTG drug. The solubilization capacity (SCP) of the binary systems was monitored using UV-Visible spectroscopy. The F127/P123 system shows relatively high solubilization capacity (SCP) due to a more hydrophobic system as copolymers with similar PPO block lengths. The F127/L35 system has been given the low SCP because of hydrophilic nature of L35. The micellar water partition coefficient (P) and Gibbs free energy changes (ΔG°) of solubilized LTG drug were also evaluated from a thermodynamics viewpoint. In conclusion, these binary micellar systems may be considered as the effective nanocarriers for LTG drug and F127/P123 mixed micelles proven better than the F127/L35 system for LTG drug.

The Influence of Electrolytes on the Mixed Micellization of Equimolar (Monomeric and Dimeric) Surfactants

The influence of halide ions of (sodium salt) electrolytes on the mixed micellization of a cationic gemini (dimeric) surfactant, hexanediyl-1,6-bis(dimethylcetylammonium) bromide (16-6-16) and a cationic conventional (monomeric) surfactant, cetyltrimethylammonium bromide (CTAB) have been investigated. The critical micelle concentration (CMC) of the mixed (16-6-16+CTAB) surfactants was measured by the surface tension measurements. The surface properties: viz., the surfactant concentration required to reduce the surface tension by 20 mN/m (C20), the surface pressure at the CMC (ΠCMC), the maximum surface excess concentration at the air/water interface (Γmax), the minimum area per surfactant molecule at the air/water interface (Amin), etc. of the mixed micellar surfactant systems were evaluated. In the absence and presence of electrolytes, the thermodynamic parameters of the mixed micellar surfactant systems were also evaluated.

Solutol HS15 based binary mixed micelles with penetration enhancers for augmented corneal delivery of sertaconazole nitrate: optimization, in vitro, ex vivo and in vivo characterization

Keratomycosis is a serious corneal disease that can cause a permanent visual disability if not treated effectively. Sertaconazole nitrate (STZ), a novel broad spectrum antifungal drug, was suggested as a promising treatment. However, its utility in the ocular route is restricted by its poor solubility, along with other problems facing the ocular delivery like short residence time, and the existing corneal barrier. Therefore, the objective of this study was to formulate STZ loaded binary mixed micelles (STZ-MMs) enriched with different penetration enhancers using thin-film hydration method, based on a 31.22 mixed factorial design. Different formulation variables were examined, namely, type of auxiliary surfactant, type of penetration enhancer, and total surfactants: drug ratio, and their effects on the solubility of STZ in MMs (SM), particle size (PS), polydispersity index (PDI), and zeta potential (ZP) were evaluated. STZ-MMs enhanced STZ aqueous solubility up to 338.82-fold compared to free STZ. Two optimized formulations (MM-8 and MM-11) based on the desirability factor (0.891 and 0.866) were selected by Design expert® software for further investigations. The optimized formulations were imaged by TEM which revealed nanosized spherical micelles. Moreover, they were examined for corneal mucoadhesion, stability upon dilution, storage effect, and ex vivo corneal permeation studies. Finally, both in vivo corneal uptake and in vivo corneal tolerance were investigated. MM-8 showed superiority in the ex vivo and in vivo permeation studies when compared to the STZ-suspension. The obtained results suggest that the aforementioned STZ loaded mixed micellar system could be an effective candidate for Keratomycosis-targeted therapy.

Brain-targeted delivery of PEGylated nano-bacitracin A against Penicillin-sensitive and -resistant Pneumococcal meningitis: formulated with RVG29 and Pluronic® P85 unimers

Pneumococcal meningitis (PM), caused by Streptococcus pneumonia, remains a high-burden disease in developing countries. Antibiotic therapy has been limited due to the inefficiency of drug transport across the blood-brain barrier (BBB) and the emergence of drug-resistant strains. In our preliminary study, PEGylated nano-self-assemblies of bacitracin A (PEGylated Nano-BA12K) demonstrated a strong antibacterial potency against S. pneumonia. In this study, the potential application of this micelle for the treatment of both Penicillin-sensitive and -resistant PM was studied. To address BBB-targeting and -crossing issues, PEGylated Nano-BA12K was formulated with a specific brain-targeting peptide (rabies virus glycopeptide-29, RVG29) and a P-glycoprotein inhibitor (Pluronic® P85 unimers) to construct a mixed micellar system (RVG29-Nano-BAP85). RVG29-Nano-BAP85 demonstrated a strong antibacterial potency against 13 clinical isolates of S. pneumonia, even higher than that of Penicillin G, a conventional anti-PM agent. RVG29-Nano-BAP85 had more cellular uptake in brain capillary endothelial cells (BCECs) and higher BBB-crossing efficiency than single formulated Nano-BAs as shown in an in vitro BBB model. The enhanced BBB-permeability was attributed to the synergetic effect of RVG29 and P85 unimers through receptor-mediated transcytosis, exhaustion of ATP, and reduction in membrane microviscosity. In vivo results further demonstrated that RVG29-Nano-BAP85 was able to accumulate in brain parenchyma as confirmed by in vivo optical imaging. In addition, RVG29-Nano-BAP85 exhibited high therapeutic efficiencies in both Penicillin-sensitive and -resistant PM mouse models with negligible systemic toxicity. Collectively, RVG29-Nano-BAP85 could effectively overcome BBB barriers and suppressed the growth of both drug-sensitive and -resistant S. pneumonia in the brain tissues, which demonstrated its potential for the treatment of PM.

Influence of urea on single and mixed micellar systems of Tetronics®

Here we report micellar and micellization characteristics of single and mixed Tetronics® altered by the presence of urea using high sensitivity differential scanning calorimetry (HSDSC) and small angle neutron scattering (SANS). Three Tetronics® with almost identical polypropylene oxide (PPO) blocks but variable polyethylene oxide (PEO) blocks viz. T1301, T1304 and T1307, were chosen for studying their solution behavior in aqueous urea (0-8M) solutions. In the case of single micellar systems, the three copolymers showed markedly different behavior.T1301 being most hydrophobic forms vesicular structures at ambient temperature, T1304 with moderate hydrophobicity forms micelles with low polydispersity while very hydrophilic T1307 exhibits high polydispersity and occur as unimers, loose micelles and clusters. The addition of urea has a disruptive effect on all the three copolymers; smaller vesicles in T1301, smaller micelles with enhanced polydispersity in T1304 and T1307 completely demicellizes to unimers and clusters as evidenced by SANS. A similar trend has also been noticed for mixed micelles. However, the phase separation temperature/critical micelle temperature (CMT) of the copolymers in binary mixtures are slightly lower as compared to the copolymer solutions of individual block copolymers in the presence of 8M urea. HSDSC measurements revealed decreased enthalpy of micellization (∆H) and increased CMT in the presence of urea suggesting enhanced solubility of the copolymer and consequently delayed micellization.

Pluronic-SAILs (surface active ionic liquids) mixed micelles as efficient hydrophobic quercetin drug carriers

The present manuscript reports a systematic investigation on the solubilization of hydrophobic drug Quercetin (QCT) in pluronic F108 and its mixed micelles with surface active ionic liquids (SAILs) having same alkyl chain length but different hydrophobic head groups viz. 1-dodecyl-3-methylimidazolium bromide [Mim]; N-dodecyl-Nmethylpiperidinium bromide, [Pip]; N-dodecyl-Nmethylpyrrolidinium bromide, [Pyr]. Employing UV–visible spectroscopy, we have determined the solubility, loading efficiency and partition coefficient of QCT in the pluronic F108 and F108-SAILs mixed micelles. The F108-SAIL mixed micellar system possessed higher solubilization capacity for QCT. Further, the effect of varying composition of mixed micelles on the solubilization of QCT has also been evaluated and discussed in detail. A significant difference between the hydrodynamic diameter (Dh) of loaded and unloaded F108 as well as F108-SAILs mixed micelles confirmed that QCT has been solubilized in these micelles. Differential pulse voltammetry (DPV) measurements have been successfully employed to determine the possible location of the QCT in the both pluronic F108 and pluronic F108-SAILs mixed micelles. These measurements indicated that most of QCT is solubilized in the core of the F108 and F108-SAILs mixed micelles. In vitro drug release study of three different F108-SAILs mixed micellar formulations show sustained release behavior according to their interaction with the QCT. Higher anticancer effects were observed in the case of micellar QCT than the free QCT confirm the efficiency of the prepared formulations. The results demonstrated that the composition of mixed micelles had a profound effect on solubilization capacity and the drug release behavior from the F108-SAILs mixed micelles can be easily tuned by changing the head group of SAILs.

Reduction-sensitive mixed micelles assembled from amphiphilic prodrugs for self-codelivery of DOX and DTX with synergistic cancer therapy

Clinically, codelivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. In this work, we developed a new reduction-sensitive mixed micellar system for self-codelivery of doxorubicin (DOX) and docetaxel (DTX). Biodegradable methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was coupled with DOX and DTX by a reduction-sensitive disulfide bond, resulting in mPEG-PCL-SS-DOX and mPEG-PCL-SS-DTX, respectively. mPEG-PCL-SS-DOX was mixed with mPEG-PCL-SS-DTX at a mole ratio of 1:1 in water, forming a mixed micellar system. The mixed micelles had a diameter of 223.7nm and a low critical micelle concentration. Reductive-triggered drug release revealed a “smart” characteristic of the mixed micelles. A cellular uptake and cytotoxicity assay in vitro showed that the mixed micelles could efficiently accumulate in MCF-7 cells and suppress the growth of tumour cells. The proposed reduction-sensitive mixed micelles assembled from amphiphilic prodrugs can be used as a promising drug codelivery system for cancer therapy.

Self-organization of mixtures of sodium oleate and imidazolium based surface active ionic liquids studied by tensiometry, rheology and neutron scattering

We report on the aggregation behavior of the mixed systems composed of sodium oleate (NaOl) with various imidazolium based ionic liquids (ILs) using tensiometry, rheometry and small angle neutron scattering (SANS). The effect of alkyl chain in 1-alkyl-3-methylimidazolium chloride, ([Cnmim][Cl], where n=4 to 10) showed that ILs with long chain length (~C10) exhibit spontaneous transition of micelles into vesicles. The comparison in ILs with same alkyl chain (C8) but with different counterions viz. chloride [Cl−], tetrafluoroborate [BF4−] and hexafluorophosphate [PF6−] showed that IL with hydrophilic ion Cl− exerts micellar transition while hydrophobic PF6− showed no noticeable effect. However, an interesting finding in this paper is the unusual behavior of IL with moderately hydrophobic BF4− that transforms micelles into vesicles. Moreover, mixed micellar systems of NaOl and IL transform into vesicular solution when pH condition turns into acidic. Tensiometric measurements disclosed strong synergistic interactions between the oppositely charged ILs and NaOl. The information on the modification of micellar characteristics of NaOl/ILs mixed system is useful for industrial applications.

Mixed aqueous solutions of nonionic surfactants Brij 35/Triton X-100: Micellar properties, solutes' partitioning from micellar liquid chromatography and modelling with COSMOmic

Aqueous solutions of nonionic surfactants are of interest for bioprocesses, particularly as solubilizing agents for hydrophobic substances. To design such processes, the data on partition coefficients of solutes between micelles and their aqueous surrounding (Pmw) are of high value. An extended understanding of the partition behavior can be achieved from the structural information such as the micelle size and micelles composition.In this work, mixtures of nonionic surfactants Triton X-100 and Brij 35 were under study. The data on critical micelle concentrations showed partly non-ideal behavior of the solutions. The compositions of mixed micelles at different molar Brij 35/Triton X-100 ratios in the surfactant mixture were estimated from the data on self-diffusion coefficients (NMR diffusometry) and were calculated within the regular solution approach and predicted by Motomura’s model. The change of the mixed micelle composition in dependence on the total surfactant concentration was observed. It has been found, that the average value of the mixed micelles radii is ∼4nm. Whereas, the polydispersity indexes and the aggregation numbers increased with Triton X-100 fraction. Moreover, the Pmw values of different non-dissociated solutes (phenyl derivatives with various functional groups) were determined by means of micellar liquid chromatography (MLC) and were predicted using the thermodynamic model COSMOmic, an extension of COSMO-RS. In general, it has been proved that COSMOmic is able to predict Pmw in the mixed micellar system formed by nonionic surfactants.The obtained data show the possibility of modulating the partition behavior of solutes using the mixtures of nonionic surfactants. Apart from the hydrophobicity, the «surfactants – solute» specific interactions play an important role in the partition behavior of the investigated systems.

Cleavable Multifunctional Targeting Mixed Micelles with Sequential pH-Triggered TAT Peptide Activation for Improved Antihepatocellular Carcinoma Efficacy.

Although tumor-targeting nanovehicles for hepatocellular carcinoma (HCC) chemotherapy have attracted great research and clinic interest, the poor cancer penetration, inefficient cellular uptake, and slow intracellular drug release greatly compromise their therapeutic outcomes. In this work, a multifunctional mixed micellar system, consisting of glycyrrhetinic acid (GA) for specific liver-targeting, trans-activator of transcription (TAT) peptide for potent cell penetration, and pH-sensitive poly(β-amino ester) polymers for acidic-triggered drug release, was developed to provide HCC-targeting delivery and pH-triggered release of doxorubicin (DOX). These micelles were hypothesized to efficaciously accumulate in HCC site by the guide of GA ligands, enter into cancer cells facilitated by the activated TAT peptide on the micellar surface, and finally rapidly release DOX in cytoplasm. To demonstrate this design, DOX was initially loaded in micelles modified with both GA and TAT (DOX/GA@TAT-M) with high drug loading efficiency and pH-sensitive drug release profiles. The HCC-targeting cellular uptake and synergetic anticancer efficacy were tested, indicating DOX/GA@TAT-M could be specifically and effectively internalized into HCC cells by the effect of GA targeting and TAT penetrating with enhanced cytotoxicity. In addition, the prolonged circulation time and enhanced accumulation in tumor facilitated its potent tumor growth inhibition activity in vivo. These results demonstrated that the cleavable multifunctional mixed micelles with tumor targeting, controlled TAT peptide activation, and sequential pH-sensitive drug release could be an efficient strategy for HCC treatment.

Sodium deoxycholate mediated enhanced solubilization and stability of hydrophobic drug Clozapine in pluronic micelles

In this report, the solubilization behaviour of a hydrophobic drug Clozapine (CLZ) in micellar suspensions of pluronics having different hydrophilic lipophilic balance (HLB) ratios viz. P84, F127 and F108 in the absence and presence of bile salt sodium deoxycholate (SDC) has been studied. UV–Vis spectroscopy has been exploited to determine the solubilization capacity of the investigated micellar systems in terms of drug loading efficiency, average number of drug molecules solubilized per micelle (ns), partition coefficient (P) and standard free energy of solubilization (∆G°). The morphological and structural changes taking place in pluronics in different concentration regimes of SDC and with the addition of drug CLZ has been explored using dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The SANS results revealed that aggregation behaviour of pluronic-SDC mixed micelles gets improved in the presence of drug. The micropolarity measurements have been performed to shed light on the locus of solubilization of the drug in pure and mixed micellar systems. The compatibility between CLZ and drug carriers (pluronics and SDC) was confirmed using powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) techniques. Among the investigated systems, P84-SDC mixed system was found to be highly efficient for CLZ loading. The long term stability data indicated that CLZ loaded P84-SDC mixed micellar formulation remained stable for 3months at room temperature. Further, it was revealed that the CLZ loaded P84-SDC mixed micelles are converted into CLZ loaded pure P84 micelles at 30-fold dilutions which remain stable up to 48-fold dilutions. The results from the present studies suggest that P84-SDC mixed micelles can serve as suitable delivery vehicles for hydrophobic drug CLZ.

Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®

Doxorubicin (DOX) is used as a “first-line” antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus®, Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7nm (PDI=0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p<0.05) higher than Doxil® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p<0.05) of the DOX intracellular content for the mixed micelles versus Doxil® for both, SKOV-3 (at 2, 4 and 6h of incubation) and MDA-MB-231 (at 4h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX.

Aggregation behaviour and solubilization capability of mixed micellar systems formed by a gemini lipoamino acid and a non-ionic surfactant

In this work we carried out the physicochemical characterization of mixtures of a non-ionic surfactant and a gemini lipoamino acid one. The mixed systems were studied by surface tension measurements, fluorescence quenching and SAXS determinations. Both surfactants formed mixed micelles in different relationships and the properties of the mixtures were more similar to those of their major component. SAXS analysis showed that the micelles were triaxial ellipsoids, type core shell. The mixtures exhibited non-ideal behaviour, as indicated by critical micelle concentrations (CMC) lower than those of the individual surfactants, and negative interaction parameters, β.The mixed surfactant systems produced enhanced water solubilization of polycyclic aromatic hydrocarbons, viz, naphthalene, phenanthrene and pyrene, quantified in terms of the molar solubilization ratio and the micelle-water partition coefficient. Synergism due to the presence of both surfactants in the mixture was observed for the solubilization of naphthalene and phenanthrene, but not for pyrene. This difference in behaviour might be related to the CMC and structure of the surfactants, the polarity of the solutes, and their association constants with the micellar phase.

Development of a new coenzyme Q10 (CoQ10) mixed micelle with high stability: Based on the thermodynamics of cloud point

Herein a more stable CoQ10-Polyoxyl (40) Stearate (S40)-Kolliphor HS15 (Polyoxyl 15 Hydroxystearate, HS15) mixed micelle system had been established from the perspective of cloud point of thermodynamics. The cloud points of micelle solutions with different S40/HS15 (w/w) were firstly measured visually and the thermodynamic parameters were evaluated simultaneously, which manifested that the mixture at the S40/HS15 ratio of 1:1 had the best thermodynamic stability. Then an innovative experiment of rotary shaker, drastically accelerating the instable aggregation, was operated to further confirm the result of clouding based on the changes of transmittances. The same method was applied to the choices of CoQ10/surfactants (w/w) and pH for the micelle system, of which the results indicated that the optimal ratio and pH were 1:6 and 4.0, respectively. It is observed that the stability of CoQ10 mixed micelle after sterilization was decreased slightly through the results of transmittance declined, cloud point decreased and surface tension value increased. The obtained results suggested the new mixed micellar system had higher cloud point and transmittance, but smaller particle number or particle size, relative to the CoQ10-HS15 individual micelle system.