Micellar Systems Research Articles

Role of Polymeric Micelles in Ocular Drug Delivery: An Overview of Decades of Research.

Local drug delivery to the eye through conventional means has faced many challenges due to three essential barriers: (a) the complex structure of the cornea limiting drug absorption, (b) the capacity of ocular absorptive cells in drug metabolism, and (c) the washing effect of eye tears. Polymeric micelles (PMs) have been the focus of much interest for ocular drug delivery due to several advantages they provide for this application, including the capacity for the solubilization of hydrophobic drugs, nonirritability, nanoscopic diameter, and the clarity of their aqueous solution not interfering with vision. The potential to increase the release and residence time of incorporated medication at the site of absorption is also a bonus advantage for these delivery systems. This Review covers research conducted on single or mixed micelles prepared from small amphiphilic molecules, copolymers (diblock, triblock, and graft), and gel systems containing micelles. The purpose of this review is to provide an update on the status of micellar ocular delivery systems for different indications, with a focus on preclinical and clinical drug development. In this context, we are discussing the anatomy of the eye, various ocular barriers, different micellar formulations, and their benefits in ocular drug delivery, as well as the role of PMs in the management of ocular diseases both in preclinical models and in clinic. The encouraging preclinical effectiveness findings from experiments conducted in both laboratory settings and live animals have paved the way for the advancement of micellar systems in clinical trials for ocular administration and the first nanomicallar formulation approved for clinical use by the United States Food and Drug Administration (marketed as Cequa by Sun Pharmaceuticals).

Copolymeric Micelles of Poly(ε-caprolactone) and Poly(methacrylic acid) as Carriers for the Oral Delivery of Resveratrol.

In this study, we report the development of a micellar system based on a poly(methacrylic acid)-b-poly(ε-caprolactone)-b-poly(methacrylic acid) triblock copolymer (PMAA16-b-PCL35-b-PMAA16) for the oral delivery of resveratrol. The micellar nanocarriers were designed to comprise a PCL core for solubilizing the poorly water-soluble drug and a hydrated PMAA corona with bioadhesive properties for providing better contact with the gastrointestinal mucosa. The micelles were first formed in an aqueous media via the solvent evaporation method and then loaded with resveratrol (72% encapsulation efficiency). Studies by transmission electron microscopy (TEM) and dynamic and electrophoretic light scattering (DLS and PALS) revealed a spherical shape, nanoscopic size (100 nm) and a negative surface charge (-30 mV) of the nanocarriers. Loading of the drug slightly decreased the hydrodynamic diameter (Dh) and increased the ƺ-potential of micelles. In vitro dissolution tests showed that 80% and 100% of resveratrol were released in 24 h in buffers with pH 1.2 and 6.8, respectively, whereas for the same time, not more than 10% of pure resveratrol was dissolved. A heat-induced albumin denaturation assay demonstrated the advantage of the aqueous micellar formulation of resveratrol, which possessed anti-inflammatory potential as high as that of the pure drug. Further, the micellar resveratrol (5 µM) exerted a strong protective effect and maintained viability of mucosa epithelial HT-29 cells in a co-cultural model, representing the production of inflammatory cytokines. For comparison, the pure resveratrol at the same concentration did not protect the damaged HT-29 cells at all. Thus, the present study revealed that the PMAA-b-PCL-b-PMAA copolymeric micelles might be considered appropriate nanocarriers for the oral delivery of resveratrol.

PH-responsive wormlike micelles formed by an anionic surfactant derived from erucic acid

An erucic acid-based anionic surfactant, AdEr, was synthesized by a simple neutralization reaction, and AdEr constructed a novel pH-responsive wormlike micellar viscoelastic system in the presence of potassium chloride (KCl). The viscoelasticity and pH-responsiveness of the pH-responsive wormlike micelles have been investigated using rheology, and its corresponding mechanism has been analyzed by Fourier transform infrared (FT-IR) spectra. The zero-shear viscosity (η0) of the AdEr/KCl system dramatically increases by 5 orders of magnitude as the pH increases from 6 to 10. The viscoelastic fluids and dispersion system with white precipitate can be converted by tuning the pH between 10.46 and 6.03, and the corresponding aggregates also transform between wormlike micelles and spherical micelles. Furthermore, by directly adding acid and alkali, the AdEr/KCl system can be precisely reversibly controlled in the pH range 6–10, and the viscosity stays unchanged after three reversible cycles, exhibiting strong pH reversibility. The pH-responsive behavior can be attributed to the manipulation of carboxylic acid protonation. This study promotes new applications of erucic acid resources in smart viscoelastic solutions.

Antioxidant Interactions between Citrus Fruit Carotenoids and Ascorbic Acid in New Models of Animal Cell Membranes.

The regular consumption of citrus fruits by humans has been associated with lower incidence of chronic-degenerative diseases, especially those mediated by free radicals. Most of the health-promoting properties of citrus fruits derive from their antioxidant content of carotenoids and ascorbic acid (ASC). In the current work we have investigated the scavenging (against hydroxyl radical) and quenching capacities (against singlet oxygen) of four different carotenoid extracts of citrus fruits in the presence or absence of ASC (μM range) in organic solvent, aqueous solution, micelles and in an innovative biomimicking liposomal system of animal cell membrane (AML). The fruits of four varieties of citrus were selected for their distinctive carotenoid composition (liquid chromatography characterization): 'Nadorcott' mandarin and the sweet oranges 'Valencia late', 'Ruby Valencia' and 'Pinalate' mutant. The quenching activity of citrus carotenoids strongly depended on the biological assemblage: freely diffusible in organic solvent, 'Ruby Valencia' carotenoids (containing lycopene) showed the highest quenching activity, whereas 'Nadorcott' mandarin extracts, rich in β-cryptoxanthin, prevailed in micellar systems. Interestingly, the addition of 10 μM ASC significantly increased the quenching activity of all citrus extracts in micelles: 'Valencia' orange (+53%), 'Pinalate' (+87%), 'Ruby' (4-fold higher) and 'Nadorcott' mandarins (+20%). Accurate C11-BODIPY581/591 fluorescence assays showed solid scavenging activities of all citrus extracts against AML oxidation: 'Valencia' (-61%), 'Pinalate' (-58%) and 'Ruby' oranges (-29%), and 'Nadorcott' mandarins (-70%). Indeed, all four citrus extracts tested here have balanced antioxidant properties; extracts from the 'Nadorcott' mandarin slightly prevailed overall, due, at least in part, to its high content of β-cryptoxanthin. This study depicts some of the antioxidant interactions between citrus fruit carotenoids and ascorbic acid in models of animal cell membranes and reinforces the contribution of them in promoting health benefits for humans.

Innovative micellar-UPLC approach for concomitant determination of favipiravir and remdesivir with four co-administered cardiovascular drugs in their pharmaceuticals and spiked plasma: Greenness and whiteness assessment

Many COVID-19 patients have pre-existing cardiovascular diseases, which are strongly linked to the high incidence of severe COVID-19. The experts advised such patients to prioritize drug treatments as per the physician's recommendations to avoid aggravation of the basic diseases. Hence, the development of an analytical approach for the concurrent determination of drugs prescribed for the co-treatment of COVID-19 and cardiovascular diseases acquires significant importance in QC units and bioavailability centers. Herein, a micellar-UPLC approach was first devised for the concomitant analysis of aspirin, atenolol, atorvastatin, losartan, favipiravir, and remdesivir as co-administered drugs, either with or without salicylic acid. On ACQUITY UPLC C18 column, the aforesaid drugs were isocratically separated employing a micellar eluent system. This system consisted of 0.03 M Brij-35, 0.15 M sodium dodecyl sulfate, and 0.02 M sodium dihydrogen phosphate (pH 5.0) as the mobile phase A (90%) and n-propanol as the mobile phase B (10%). The eluent system was pumped at a flow rate of 0.50 mL.min−1 for 5.50 min, which was suddenly increased to 0.80 mL.min−1 for 2.50 min. The separated peaks were scanned at 240 nm. The suggested approach was validated following ICH requirements for linearity, robustness, accuracy, specificity, precision, and detection and quantitation limits. The suggested approach was applied successfully to commercial products and human plasma without any intrusion from excipients or plasma matrices. The suggested approach’s greenness was appraised employing five metrics namely: eco-scale, GAPI, NEMI, Raynie and Driver, and AGREE. Furthermore, the suggested approach’s whiteness features were investigated using the recently unveiled RGB12 model. The suggested approach outperformed the reported approaches in terms of greenness and whiteness. The sensitivity, high sample throughput, and short runtime (7.40 min) of the suggested approach assert its aptness for routine determination of the aforesaid drugs.

Sulfur dioxide-releasing polymeric micelles based on modified hyaluronic acid for combined cancer therapy

In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO2. In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO2 and PTX.

Potential Role of Bromelain in Wound Healing Application: A Review

Bromelain is a proteolytic enzyme derived from the pineapple plant (Ananas comosus). Bromelain can be extracted from pineapple stems and fruits. Additionally, it can be derived from pineapple wastes such as the core, crown, and peel. Various extraction and purification methods such as reverse micellar system, aqueous two-phase system, chromatographic techniques, and membrane filtration have been used in order to produce high-qualitybromelain. Bromelain has been used clinically since 1876 and was first introduced as a therapeutic agent in 1957. Bromelain has gained increasing acceptance and compliance among patients as a phytotherapeutic drug due to its safety and lack of undesirable side effects. Bromelain is regarded as a nutrient that promotes wound healing due to the presence of several closely related proteinases that exhibit anti-inflammatory, fibrinolytic, and debridement properties.

On-line preconcentration of fluorescein derivatives of essential amino acids using sweeping in a nonionic micellar system

A rapid and effective method of nonionic micellar electrokinetic chromatography with laser-induced fluorescence detection and sweeping as an online preconcentration method was developed for the simultaneous determination of free essential amino acids in supplement formulations. The analytes were derivatized using fluorescein isothiocyanate isomer I dissolved in dimethyl sulfoxide. Optimal separation conditions were achieved using an uncoated fused silica capillary (40.0 cm effective length, 50.2 cm total length, 50 µm internal diameter), 20 mM Na2B4O7, (pH 9.3), 50 mM Brij-35, and 15% (v v-1) methanol as running buffer. Complete separation of all analytes was achieved within 15 min. The optimized method exhibited good linearity (r2 > 0.997), acceptable precision (1.3 – 12.4%), and accuracy (88 – 112%) in concentration range 20 – 1000 ng mL−1. The limit of detection was 6 ng mL−1. The method successfully determined the quantity of free essential amino acids in a dietary supplement containing spirulina.

Binary Pluronics based mixed micellar systems: Effective solution for improved solubilization of Biochanin A

The present work was carried out to appraise the solubilization of Biochanin (BCA), a natural hydrophobic drug in pure Pluronics (P84, P123 and F127) as well as binary mixed micelles (P84-P123 and F127-P123) followed by an interactional study using various state of art techniques. The critical micelle concentration (CMC) of binary mixtures P84-P123 and F127-P123 was found to be significantly lower than pure Pluronics justifying the candidature of mixed micelles (MMs) as a better solubilizer for BCA. UV–visible studies revealed the enhanced solubility of BCA in P84-P123 (1:2) MMs (3.51 ± 0.087 mg/mL) and F127-P123 (1:2) MMs (2.94 ± 0.046 mg/mL) as compared to micelles of pure Pluronics (10% w/v), P84 (2.25 ± 0.039 mg/mL) and F127 (1.12 ± 0.036 mg/mL). Differential pulse voltammetry (DPV) results demonstrated significantly superior binding of BCA with P84-P123 (1:2) MM (Ka = 2.60 × 105 M−1) as compared to pure P84 (Ka = 1.415 × 105 M−1). Mixed micellization (P84-P123 (1:2)) leads to increase in micellar hydrodynamic diameter (Dh = 16.09 nm) as compared to pure Pluronic P84 micelles (Dh = 15.71 nm) which was further amplified (Dh = 17.69 nm) after BCA loading. Different formulations of pure and MMs were subjected to in vitro drug release and MMs were found to slow down BCA release as compared to pure Pluronics (P84, P123). The results obtained in this study proved that P84-P123 (1:2) MMs are superior and more effective for the solubilization of BCA than pure and other MMs. Thus, the examined MMs hold the potential for advancing the development of solubilization techniques for other hydrophobic drugs with significant pharmacological value.

Development of Novel Formulation for Sustained Release of Drug to Prevent Swainsonine-Containing Plants Poisoning in Livestock.

Swainsonine-containing plants contain swainsonine which has been shown to cause neurological signs and pathological changes in farm animals. It causes a large number of livestock poisonings every year resulting in economic losses to the livestock industry. At present, "Jifang E" is used in the prevention of swainsonine-containing plants poisoning livestock, and the preventive effects have been well-documented. However, "Jifang E" is typically administered in drinking water, making it difficult to control the administered dosage, because of feeding difficulties and it may cause certain side effects that are unique to the water-dissolved powder. To overcome these difficulties, we developed a temperature-sensitive gel for injection and the optimal ratio of each formula of sustained-release injection is P407 (24%), P188 (6%), Vitamin C (1%), PEG4000 (0.5%), and "Jifang E" (10%). Our results suggest that novel formulation makes the micellar system more stable and the particles are uniformly dispersed. Colloidal morphological studies showed that each group formed a homogeneous pore structure after gelling, and the structure became more dense with the addition of "Jifang E". The rheological study shows that "Jifang E" is a pseudoplastic fluid, and the addition of "Jifang E" reduces the viscosity of the formula, which is beneficial to the injection. In vitro and in vivo release rate studies have shown that the effective concentration of "Jifang E" can be maintained for 3 to 5 days. The acute toxicity test in SPF Kunming mice showed that its LD50 was 828.323 mg/kg, with confidence limits of 676.706-1013.911 mg/kg, which is a safe dosage (LD50 > 200 mg/kg). There were no observed reactions of muscle irritation or subcutaneous tissue irritation with the dosage used for New Zealand rabbits. In summary, we successfully developed the sustained-release injection formulation of "Jifang E" for the prevention of swainsonine-containing plants poisoning livestock, which provides the basis for subsequent field extension trials and the further study of its detoxification mechanism.

Photophysics of 7-hydroxycoumarin 3-carboxylic acid in micelles

7-Hydroxy coumarin-3-carboxylic acid (7-HCCA) is a photoacid that exists in three distinct forms: neutral, anionic and di-anionic. It falls under the category of hydroxy aromatic and carboxy aromatic molecules. This molecule exhibits strong fluorescence and is commonly employed in the detection of hydroxyl radicals. In our study, we utilised absorption and fluorescence spectroscopy to investigate the photophysical behaviour of 7-HCCA in different micellar systems. Through our experiments, we observed that as we varied the pH within the ranges of 2–3, 4–6, 7–10, the three aforementioned forms of 7-HCCA are emerged. Specifically, in cationic surfactants, the dye displayed an equilibrium between two forms of the 7-HCCA in the ground state at any pH. Furthermore, our steady-state excitation studies also proved the presence of an equilibrium between two forms of the 7-HCCA in all cationic systems. By examining the steady-state emission spectra, we also observed the presence of two distinct species in the excited state. When cationic surfactants were introduced, we observed a decrease in the fluorescence intensity and quantum yield compared to that observed in the water medium. It was evident that the photophysical properties of 7-HCCA were modulated with variations of the chain length and head group of the surfactants. In summary, our investigation shed light on the photophysical characteristics of 7-HCCA in different micellar systems with varying the pH. By employing the absorption and fluorescence spectroscopy, we successfully identified the coexistence of multiple forms of 7-HCCA and observed how the cationic surfactants influenced its fluorescence emission properties, ultimately contributing to a deeper understanding of its behaviour in these systems.

Green removal of low and high levels of Cu(II) and Cr(III) cations from concentrated saline chloride medium achieved by a mixture of N,N′-bis(salicylidene)-thiocarbohydrazide-TritonX-100 micellar system via cloud point extraction process

Abstract In this work, we performed the cloud point extraction with low and high concentrations of Cu(II) and Cr(III), two particularly toxic metallic pollutants, that have been shown to have adverse effects on human health and the environment. Removal of the metal ions was achieved in the presence of Triton X-100 as a non-ionic surfactant and N,N′-bis(salicylidene)-thiocarbohydrazide as a chelating ligand in concentrated chloride medium. The behavior of the Schiff base was initially investigated in homogeneous DMSO-water and micellar Triton X-100-water media. The obtained values of the acid constants show that the extractant is more acidic in micellar media than in pure aqueous medium. The recorded cloud point temperatures of Triton X-100 are significantly impacted by the sodium chloride concentration, the surfactant concentration, and the Schiff base ligand. Under the optimised experimental conditions, a quantitative extraction of Cu(II) and a maximum extraction rate of 74 % of Cr(III) were obtained. The reduction of the metal concentration from 10−3 mol L−1 to 10−6 mol L−1 resulted in a reduction of the temperature by 10 °C and a reduction of the contact time from 10 h to 3 h.

Collection of Partition Coefficients in Hexadecyltrimethylammonium Bromide, Sodium Cholate, and Lithium Perfluorooctanesulfonate Micellar Solutions: Experimental Determination and Computational Predictions.

This study focuses on determining the partition coefficients (logP) of a diverse set of 63 molecules in three distinct micellar systems: hexadecyltrimethylammonium bromide (HTAB), sodium cholate (SC), and lithium perfluorooctanesulfonate (LPFOS). The experimental log p values were obtained through micellar electrokinetic chromatography (MEKC) experiments, conducted under controlled pH conditions. Then, Quantum Mechanics (QM) and machine learning approaches are proposed for the prediction of the partition coefficients in these three micellar systems. In the applied QM approach, the experimentally obtained partition coefficients were correlated with the calculated values for the case of the 15 solvent mixtures. Using Density Function Theory (DFT) with the B3LYP functional, we calculated the solvation free energies of 63 molecules in these 16 solvents. The combined data from the experimental partition coefficients in the three micellar formulations showed that the 1-propanol/water combination demonstrated the best agreement with the experimental partition coefficients for the SC and HTAB micelles. Moreover, we employed the SVM approach and k-means clustering based on the generation of the chemical descriptor space. The analysis revealed distinct partitioning patterns associated with specific characteristic features within each identified class. These results indicate the utility of the combined techniques when we want an efficient and quicker model for predicting partition coefficients in diverse micelles.

Polymeric micelles as a strategy to enhance the phototoxic efficacy of phenazine photosensitizers

AbstractAntimicrobial photodynamic therapy (aPDT) is a promising therapeutic strategy for treating bacterial infections resistant to conventional antibiotics. In the search for ideal photosensitizers (PSs), we became interested in phenazine compounds, such as Neutral Red (NR) and its halogenated derivative (NRBr). Although they have shown good results in the inactivation of Staphylococcus aureus in their free form, they have some undesirable properties that could be overcome by using drug delivery systems. In this work, we propose the use of polymeric micelles for the development of nanophotosensitizers from Pluronic P123 and F108. The micellar systems developed had a size close to 30–40 nm and allowed us to obtain seven nanophotosensitizers. All of them increased the chemical stability of NRBr and did not modify the stability of NR, which was already stable in buffer solution (pH = 7.4). Furthermore, the Pluronic micelles markedly decreased the aggregation of PSs and increased their photochemical reactivity. The nanophotosensitizers prepared from Pluronic P123 micelles (5% wt/vol) gave the best results and optimized the properties of NR and NRBr. In agreement with that, the new nanophotosensitizers of P123‐5% showed better photodynamic inactivation of NR and NRBr against methicillin resistant S. aureus than the free photosensitizers and the other micellar systems. Both photosensitizers loaded into the P123‐5% eradicated this microorganism using 30 min of irradiation. Therefore, it is concluded that these polymeric micelles are an excellent alternative for the vehiculization of PSs and that their combination with NR and NRBr enhances the photodynamic efficiency for their use in aPDT.

UV-Visible study on the solubilization of solvatochromic-origin dyes in various micellar systems

The evaluation of interactions between surfactants and dyes is an important challenge for a wide variety of scientific fields, contributing significantly to industrial development. Understanding the interactions between dyes of various classes and surfactants of different types can improve many processes in the future, such as enabling better capture of harmful dyes as industrial waste, thus facilitating their neutralization. In the pharmaceutical industry, there is a constant need to improve the design of new carriers for surfactant-stabilized drugs. Various dyes are very often successfully used as model molecules for therapeutic and/or diagnostic agents. In this regard, the present study evaluated the micellar solubilization of two dyes with different types of solvatochromism - Disperse Orange 3 and 2,6-dichloro-4-(2,4,6-triphenyl-1-pyridino)phenolate. A wide range of surfactants of different chemical natures - ionic (including cationic, anionic, and amphoteric) and nonionic ones - were used to form supramolecular micellar structures. Some shifts in the position of the absorption bands for ionic surfactants were observed, and the results suggest that they have a better ability for micellar solubilization, while having a higher solvatochromic behavior. The results were also compared with spectra for pure solvents allowing a broader determination of the resulting micellar aggregates’ polarity and indicating their place in the widely used ET(30) scale. Experimental studies indicate that both model molecules are not localized in the core, but are located in the more external part of the micelle. This approach allowed us to assess the solubilization of the dyes using each representative surfactant, thereby providing insights into their interaction with micellar systems. This comprehensive analysis allows for a more holistic understanding of the solubilization process and provides insights into the influence of surfactant charge on the solubilization efficiency. Moreover, the extended set of the surfactants as well as chromophores exhibiting different solvatochromic behavior takes account of our considerations and allows a deeper look at the solvatochromic phenomenon in the context of micelle-chromophore interactions.

Dual natural antioxidant‐loaded chitosan‐graft‐oleic acid micelles by ultrasound‐assisted self‐assembly: Potential additives for antioxidant active packaging

AbstractNatural antioxidants are beneficial additives for active packaging due to their ability to resist oxidative damage. Polymeric micelles are effective in delivering natural antioxidants in aqueous environments. However, individual encapsulation of a single antioxidant may not be sufficient to meet the needs of modern food packaging. A dual natural antioxidant‐loaded micellar system (i.e., vitamin E [VE] and curcumin [Cur]) was developed to achieve combined functionality and high loading concentration. Chitosan‐graft‐oleic acid (CSOA) micelles were employed as carriers to co‐encapsulate VE and Cur through a facile ultrasound‐assisted self‐assembly method. The prepared VE and Cur co‐loaded micelles (CSOA/VE/Cur) exhibited a uniform spherical structure with an average particle size of 210.6 nm and a zeta potential of +29.5 mV. Moreover, the co‐encapsulation of VE and Cur showed a significant enhancement in both entrapment efficiency, loading capacity and stability as compared to the individual encapsulation of either VE or Cur. In addition, the CSOA/VE/Cur micelles showed improved antioxidant activity than free VE/Cur at the same concentrations, as evidenced by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Moreover, the micellar materials were utilized to fabricate regenerated cellulose (RC) films with antioxidant properties, highlighting their potential as additives for antioxidant active packaging.

Analyzing the modulations induced in the mixed micellar behavior of 1-alkyl-3-butylimidazolium based surface-active ionic liquids with an antibiotic drug in aqueous media

Abstract The study aims to scrutinize the mixed micellization and interfacial behavior of two 1-alkyl-3-butylimidazolium based surface-active ionic liquids (SAILs) i.e., 1-decyl-3-butylimidazolium bromide [C10bim][Br] and 1-tetradecyl-3-butylimidazolium bromide [C14bim][Br] under the influence of streptomycin sulphate (SS) drug in 5 mM concentration in aqueous media. Imidazolium-based SAILs have unique physicochemical properties and greater surface activity than conventional surfactants, which allows them to increase drug permeability, making them better drug carriers than currently available formulations. To fully utilize [C14bim][Br] and [C10bim][Br] in drug delivery applications, deep insight into the interactions occurring in the mixed micellar [C10bim][Br]/[C14bim][Br] systems in the drug’s presence are necessary to be examined. Thus, the study is conducted using conductivity and surface tension measurement techniques to fully exploit the self-assembly, micellization behavior and interactions occurring in the pure and mixed micellar system of [C10bim][Br]/[C14bim][Br] in water and 5 mM of SS solution in aqueous media. For this, various thermodynamic, surface-active and mixed micellar parameters of micellization have been calculated and analyzed with respect to change in mole fraction, temperature and addition of SS in solution.

Dyeing of Linen Fabrics in Supercritical CO2 Using a Reverse Micellar System with Ionic Liquid Domains

ABSTRACT In order to realize the anhydrous dyeing of linen fabric with reactive dyes in supercritical CO2, a supercritical CO2 ionic liquid reverse micelle system was constructed, and the dyeing process of linen fabric in this system was studied. In this system, linen fabric can be dyed with reactive dyes without special pretreatment. The results show that the dyeing depth of linen fabric can be significantly improved by increasing the amount of surfactant. With the increase in temperature, the dyeing depth first increases and then decreases. The dyeing pressure displays little effect on the dyeing depth. After dyeing, there are a lot of floating colors on the surface of the fabric. Increasing the temperature and prolonging the dyeing time are conducive to dye fixation on the fabric. Adding a certain amount of dimethyl sulfoxide (DMSO) to the system can improve the dyeing performance significantly. In this paper, the best dyeing conditions of linen fabric are as follows: w, 1.2; surfactant conc. 3.5 × 10−2 g/mL; T, 90°C; t, 180 min; p, 21MPa; DMSO concentration, 76.8 mmol/L.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery

Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.

Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells.

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.