Micellar Systems Research Articles

Highly effective corneal permeability of reactive oxygen species-responsive nano-formulation encapsulated cyclosporine a for dry eye management

Dry eye disease (DED) has become a globally recognized public health problem with complex pathogenesis. Recent studies showed that oxidative stress damage and its induced inflammation are the main contributors to the occurrence and progression of dry eye. Here, a novel antioxidative and reactive oxygen species (ROS)-responsive micellar system is reported to improve the ocular surface delivery of highly hydrophobic immunosuppressive cyclosporine A (CSA). This drug carrier is utilized together with the loaded anti-inflammatory drug to achieve a combinatorial treatment of DED. In detail, the selenium substituted random copolymer Se-PEG-PPG is the key to such design, which self-assembles into cornea-penetrating nanoscale micelles with a neutral shell and small size (<50 nm). The Se-PEG-PPG micelles also exerted synergetic therapeutic effects by decreasing intracellular oxidative stress and inhibiting cell apoptosis because of the ROS-scavenging selenium ether group. Finally, the combinatorial anti-oxidation, anti-inflammation, and therapeutic effects of CSA@Se-PEG-PPG eye drops were demonstrated in a murine dry eye model. Taken together, this multifunctional drug delivery system provides a promising approach for the treatment of DED and various ROS-related ocular diseases.

Impact of carbocyclic sugar-based myo-inositol on conventional surfactants

Surfactants and inositol are examples of eco-friendly components that seem to be sustainable in chemistry. The hydrophilic portion of myo-inositol (MI) may be effective in increasing the superficial activity of the micellar systems. It is possible to modify and enhance the aggregation properties of surfactants by selecting suitable additives such as MI. The impact of carbocyclic sugar-based MI on conventional surfactants such as Triton X-100 (TX-100), cetyltrimethylammonium bromide (CTAB), and sodium dodecyl sulfate (SDS) was performed by electrical conductivity, viscometer, colorimetry, stalagmometer, dynamic light scattering (DLS) and FTIR methods. The main focus of this paper was to determine the critical micelle concentration (CMC), hydrodynamic radii (Rh), zeta potential (ζ), various interfacial parameters viz., the surface tension at CMC (γCMC), the surface pressure at CMC (πCMC), the efficiency of adsorption pC20, the minimum surface area per molecule (Amin), the maximum surface excess concentration (Гmax), and thermodynamic parameters i.e., the standard Gibbs free energy of adsorption (ΔG°ads), the standard Gibbs free energy of transfer (ΔG°trans), the standard Gibbs free energy of air–water interface (ΔGsmin), the standard Gibbs free energy of micellization (ΔGom), the standard Gibbs free energy of micellization per alkyl tail (ΔG°tail). A significant decrease in the CMC values of all conventional surfactants was reported with the addition of different concentrations of MI (mM) and its conformational study by colorimetric method. The higher negative values of ΔG°m and ΔG°ads have been shown the micellization and adsorption properties became more spontaneous. Relative viscosity-based rheological behaviour was calculated for various surfactant-MI systems. The DLS and FTIR spectra were used to reveal the improved micellization behaviour of conventional surfactant-MI systems. The FTIR data showed that the CTAB-MI and SDS-MI systems have significantly influenced the stretching frequency as compared to the TX-100-MI system. The present works will apply to drug delivery, agrochemical, molecular biology, and pharmaceutical sciences.

Dyeing of polyamide fabrics with a reverse micellar system using soybean oil as a solvent

AbstractThe current study reports the results of non‐aqueous dyeing on polyamide fabrics based on a reverse micellar system composed of a stable emulsion of soybean oil, a co‐surfactant, a nonionic surfactant and acid dyes. The system does not make use of water or electrolytes and significantly reduces the dyebath volume. The influence of the hydrophilic lipophilic balance of the surfactants was evaluated, and it was found that the more hydrophilic the surfactant, the better the interaction of the reverse micellar emulsion with the substrate and, consequently, the greater the resulting colour strength. The co‐surfactant plays an important role in the system, as its proportion to the surfactant/oil mixture is directly related to better exhaustion of the dyebath. The results were compared with those from a conventional water‐based dyeing system. Colour matching was performed using the CIELab colour difference formula (ΔE) measured by a reflectance spectrophotometer.

Gradient tumor microenvironment-promoted penetrating micelles for hypoxia relief and immunosuppression reversion in pancreatic cancer treatment

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is the main block for the penetration of chemotherapy. In the tumor microenvironment, a dense matrix composed of fibrin is formed on the exterior, while the interior is featured by high reduction, hypoxia and low pH. How to match the special microenvironment to on-demand drug release is the key to improve chemotherapeutic efficacy. Herein, a microenvironment-responsive micellar system is developed to deepen tumoral penetration. Briefly, the conjugation of a fibrin-targeting peptide to PEG-poly amino acid has been utilized to achieve accumulation of micelles in the tumor stroma. By modification of micelles with hypoxia-reducible nitroimidazole which becomes protonated under acidic conditions, their surface charge is more positive, facilitating deeper penetration into tumors. Paclitaxel was loaded onto the micelles via a disulfide bond to enable glutathione (GSH)-responsive release. Therefore, the immunosuppressive microenvironment is relived through the alleviation of hypoxia and depletion of GSH. Hopefully, this work could establish paradigms by designing sophisticated drug-delivery systems to tactfully employ and retroact the tamed tumoral microenvironment to improve the therapeutic efficacy based on understanding the multiple hallmarks and learning the mutual regulation. Statement of significanceTumor microenvironment(TME) is an unique pathological feature of pancreatic cancer and an inherent barrier to chemotherapy. Numerous studies regard TME as the targets for drug delivery. In this work, we propose a hypoxia-responsive nanomicellar drug delivery system that aiming hypoxia TME of pancreatic cancer. The nanodrug delivery system could respond to the hypoxic microenvironment and enhance the penetration of the inner tumor at the same time preserving the outer tumor stroma, thus achieving targeted treatment of PDAC by preserving the integrity of the outer stroma. Simultaneously, the responsive group can reverse the degree of hypoxia in TME by disrupting the redox balance in the tumor region, thus achieving precise treatment of PDAC by matching the pathological characteristics of TME. We believe our article would provide new design ideas for the future treatments for pancreatic cancer.

Origin of steady state stress fluctuations in a shear-thinning worm-like micellar system

Large, irregular stress fluctuations under a constant applied shear rate are observed during the flow of dilute worm-like micellar solutions even at low Reynolds numbers. Statistical properties of such fluctuations showing signatures of chaos and elastic turbulence have been studied extensively. Although the mechanisms like boundary slippage, dynamics of shear band interface, time-dependent secondary flows, and inertio-elastic effects are conceived as the possible factors for such striking flow properties, their contributions in different non-linear flow regimes remain poorly understood. Here, we study the Taylor–Couette flow of a well-characterized aqueous worm-like micellar system formed by 2 wt. % cetyltrimethylammonium tosylate and 100 mM sodium chloride (2 wt. % CTAT + 100 mM NaCl). For a fixed applied shear-rate just beyond the onset of shear-thinning, high-speed optical imaging in the flow-gradient plane reveals spatiotemporally varying velocity gradients in the system. In this regime, the magnitude of stress fluctuations remains insignificant. However, the fluctuation becomes substantial beyond a critical shear rate deep inside the non-linear regime of the flow curve when significant free-surface undulations, sustained stick-slip, and elastic recoil events are observed. Imaging in the flow-vorticity and the gradient-vorticity plane indicates that such dynamics are primarily driven by the elasticity-induced turbulent flows in the system. Furthermore, in this regime, we find that the characteristic persistent time of stress fluctuations matches well with the time scales of the stick-slip events, as well as the micellar breaking time, indicating a possible connection between the striking stress dynamics and the micellar kinetics.

Shear banding predictions for wormlike micellar systems under a contraction–expansion complex flow

This study focuses on computational modeling of shear-banded wormlike micellar solutions (WLM) in a complex planar Couette flow, driven by a moving top plate over a rounded-corner 4:1:4 obstruction. The BMP+_τp model is used, which is constructed within an Oldroyd-B-like form, coupled with a thixotropic fluidity-based structure equation. Solute energy dissipation drives fluid–structure adjustment in a construction–destruction dynamics affected by viscoelasticity. This model reproduces conventional WLM features, such as shear thinning, extensional hardening/softening, viscoelasticity, apparent yield stress, and shear banding, with a bounded extensional viscosity and an N1Shear upturn at high deformation rates. The BMP+_τp characterization for shear banding is based on extremely low solvent fractions and appropriate shear-banding intensity parameters. Flow structure is analyzed through velocity, stress, and fluidity, whereupon banded and non-banded response is contrasted at appropriately selected flow rates. Solutions are obtained with our hybrid fe-fv algorithm, capturing essential shear-banded flow features reported experimentally. For a fluid exhibiting banding, banded solutions are generated at a flow rate within the flow curve unstable branch. In the fully developed simple shear flow regions, a split velocity profile is observed, with different viscosity bands at equal stress levels, enhanced with a shock-capture procedure. Non-banded solutions are derived for the lowest and highest flow rates sampled, located in the stable branches. Within the constriction zone, banded profiles are lost due to the mixed non-homogeneous deformation. Shear-banding fluids display less intense viscosity/stress features, correlated with their relatively stronger shear thinning response. The constriction resistance provokes a pressure-level adjustment, leading to fully developed Couette-like constant values upstream–downstream.

Nanoscale Pluronic® micellar templates with varying %EO content for controlled drug release and cytotoxicity

This study investigates the self-assembly in ethylene oxide (EO)-propylene oxide (PO)-based block copolymers (BCPs) with various molecular features like molecular weight, EO/PO ratio, HLB (Hydrophobic lipophilic balance) in aqueous solution environment. Our BCP solution systems exhibit significant changes in solution behaviour that showed micellization, micelle growth/ transition, and progressively phase separation (2ϕ), all of which are well explained by clear solution, blue point (BP) and cloud Point (CP) respectively. The solubilization of the highly hydrophobic anticancer drug-Quercetin (QCT) in such BCPs is examined using UV–Visible spectroscopy. The spectral findings inferred the dissolution capability of QCT in the examined copolymeric micellar systems in terms of drug loading efficiency (DL%), encapsulation efficiency (EE%), partition coefficient (P), and standard free energy of solubilization (ΔGo). Amongst the varied tested BCPs, it was observed that Pluronics® P123 and F127 exhibited an enhanced QCT solubilization capability than others and is explained in terms of hydrophobicity and hydrophilicity. The micellar size distribution profile expressed as hydrodynamic diameter (Dh) was determined for QCT-loaded and QCT-unloaded BCP micelles employing dynamic light scattering (DLS). The drug release profile was fitted employing various kinetic models, allowing this study to serve as an excellent foundation for QCT delivery. Reversed-phase High-performance liquid chromatography (HPLC) system determined the retention period in the QCT-loaded micelle while the structural alterations involved in Pluronics®-QCT system is inferred using small-angle neutron scattering (SANS). Fourier transform infrared spectroscopy (FT-IR) depicted the compatibility between Pluronics® and QCT which was validated further from the evaluated optimum descriptors using Gaussian 09 computational simulation framework. It was discovered that the QCT-loaded micelles exhibited a greater anticancer effect than free drug when tested in vivo on cancer cells. The anticancer activity of QCT-loaded F127 micelles was determined to be the strongest. Thus, the current study on QCT solubilization in Pluronics® will benefit considerably from its investigated outcomes.

Synthesis of a Reactive Oxygen Species Responsive Star Polymer for the Controlled Release of Carbendazim

An intelligent responsive pesticide delivery system has been applied in agriculture to improve the utilization rate of pesticides. When plants are affected by fungi, a large number of reactive oxygen species (ROS) are produced rapidly on the wound surface. Based on this, a ROS responsive star polymer micellar slow-release system was constructed to load carbendazim (MBC) and improve its bioavailability. The star polymer was synthesized by using 3-mercaptopropionic acid, acetone, pentaerythritol (PER), ε-caprolactone (ε-CL), and methoxypolyethylene glycols (mPEG5000, Mw = 5000) and named PER-PCL-TK-mPEG5000. By loading MBC, the drug loading micelle MBC-loaded PER-PCL-TK-mPEG5000 was obtained. The cumulative release amount of MBC-loaded PER-PCL-TK-mPEG5000 containing H2O2 is 1.64 times of that without H2O2 after 120 h release. The inhibitory rate of MBC-loaded PER-PCL-TK-mPEG5000 containing H2O2 against Rhizoctonia solani (R. solani) was 91.6%. The critical micelle concentration (CMC) of PER-PCL-TK-mPEG5000 is 4.37 mg/L, and the result showed that PER-PCL-TK-mPEG5000 and MBC-loaded PER-PCL-TK-mPEG5000 have good stability at 4 °C for 14 d. This study proved that the strategy of designing pesticide vectors according to the target environment can be widely used to protect crops, improve pesticide utilization rate, and protect the environment.

Direct Quantification of Serum Protein Interactions with PEGylated Micelle Nanocarriers.

A large repertoire of nanocarrier (NC) technologies exists, each with highly specified advantages in terms of targetability, stability, and immunological inertness. The characterization of such NC properties within physiological conditions is essential for the development of optimized drug delivery systems. One method that is well established for reducing premature elimination by avoiding protein adsorption on NCs is surface functionalization with poly(ethylene glycol) (PEG), aptly called PEGylation. However, recent studies revealed that some PEGylated NCs have a delayed immune response, indicating the occurrence of protein-NC interactions. Obvious protein-NC interactions, especially in micellar systems, may have been overlooked as many early studies relied on techniques less sensitive to molecular level interactions. More sensitive techniques have been developed, but a major challenge is the direct measurement of interactions, which must be done in situ, as micelle assemblies are dynamic. Here, we report the use of pulsed-interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) to interrogate the interactions between two PEG-based micelle models and serum albumin protein to compare protein adsorption differences based on linear or cyclic PEG architectures. First, by measuring micelle diffusion in isolated and mixed solutions, we confirmed the thermal stability of diblock and triblock copolymer micelle assemblies. Further, we measured the co-diffusion of micelles and serum proteins, the magnitudes of which increased with concentration and continued incubation. The results demonstrate that PIE-FCCS is capable of measuring direct interactions between fluorescently labeled NC and serum proteins, even at concentrations 500 times lower than those observed physiologically. This capability showcases the potential utility of PIE-FCCS in the characterization of drug delivery systems in biomimetic conditions.

Development and evaluation of azithromycin dihydrate in single and binary micellar mediums

Azithromycin (AZI) has poor aqueous solubility and very low bioavailability. In this study, two nonionic polymeric surfactants, namely Pluronic L-35, and Pluronic P-123, and their binary micelle was used for entrapment of drug AZI. The drug-encapsulated micelles were characterized by UV-spectrophotometry, FTIR, Cloud point, Partition coefficient, and antibacterial studies. We observed improved solubilization of the drug AZI in the binary micellar formulation than in their single micellar systems. The FTIR studies inferred that there is a stable, strong bond formation of the drug AZI with the binary micelle. The partition coefficient values too pointed towards higher solubility of drug AZI in mixed micellar systems as compared to single micellar systems. The free energy of micellization ∆Gomic as determined from the partition coefficient displayed negative values for all three systems indicating spontaneous binding between the drug AZI with the polymeric micellar systems. The highest negative value (-3192.6 kJ/mol) for AZI in the binary system compared to AZI-L-35 (-1620.3 kJ/mol) and AZI-P-123 (-2752.8 kJ/mol) concludes that the drug AZI is better partitioned in the binary micellar system than in the two single micellar solutions. This study can be considered as a potential solubilizing medium for the drug AZI. This is probably the first report of AZI in binary micellar solution.

Pluronic® P-123 as a reductant and stabilizing agent for gold nanoparticles (AuNPs) combined with methylene blue for photodynamic and photothermal therapy

The search for more effective drugs and therapies for the treatment of microbial diseases has driven the development of nanomedicine in recent years. In this sense, the present work shows the combination of photodynamic therapy (PDT) and photothermal therapy (PTT) using the photoactive drugs: methylene blue (MB) and gold nanoparticles (AuNPs). The ABA triblock Pluronic® P-123 copolymer was employed both as a micellar nanocarrier and reductant/stabilizing agent for AuNPs. The synthesis of gold nanoparticles (AuNPs) was carried out in situ through the redox process of AuCl3 gold salt in the presence of different concentrations of P-123 ranging from 0.25 % to 8.00 % ( % w/V) following the solid dispersion method. The MB was incorporated into the copolymeric micellar system by passive and active incorporation methods. In general, the system containing 1.00 % and 2.00 % (w/V) of P-123 was the more efficient and reproducible to obtain P-123/AuNPs/MB samples. The AuNPs synthesized presented plasmonic resonance peaks ranging from 535 to 554 nm, characteristic of spherical AuNPs. Dynamic Light Scattering and transmission electronic microscopy confirm the structure of the polymeric micelle around 20 nm and the AuNPs 3 nm diameters. The fluorescence emission showed to be dependent on the excitation wavelength, a promising feature for biological applications, especially when considering an image-guided diagnosis. Furthermore, the Stern-Volmer study by fluorescence quenching with iodide showed that active incorporation favors greater internalization of MB at the hydrophobic core of the micelle. On the other hand, the passive incorporation method placed MB in the most hydrophilic region in the micelle. The photodynamic effect was confirmed by singlet oxygen generation using ABDA as a probe. Thermal Lens spectroscopy and heating studies also confirms the heat generation by the system. In addition, the results point to synergism both in the generation of 1O2 and heat. The in vitro susceptibility of the samples was evaluated in Candida albicans strain. Better antifungal activity was observed in the sample of 2.00 % P-123/AuNPs/MB by Passive incorporation, illuminated with red and green LEDs. The biological study in bacteria strains of E. coli and S. aureus has shown that both percentages of P-123 with MB and AuNPs/MB by passive incorporation were efficient in controlling the evaluated bacteria. In this way, the present work showed promise for the treatment of antimicrobials through the combined therapy of PDT and PTT.

When self-assembly meets interfacial polymerization.

Interfacial polymerization (IP) and self-assembly are two thermodynamically different processes involving an interface in their systems. When the two systems are incorporated, the interface will exhibit extraordinary characteristics and generate structural and morphological transformation. In this work, an ultrapermeable polyamide (PA) reverse osmosis (RO) membrane with crumpled surface morphology and enlarged free volume was fabricated via IP reaction with the introduction of self-assembled surfactant micellar system. The mechanisms of the formation of crumpled nanostructures were elucidated via multiscale simulations. The electrostatic interactions among m-phenylenediamine (MPD) molecules, surfactant monolayer and micelles, lead to disruption of the monolayer at the interface, which in turn shapes the initial pattern formation of the PA layer. The interfacial instability brought about by these molecular interactions promotes the formation of crumpled PA layer with larger effective surface area, facilitating the enhanced water transport. This work provides valuable insights into the mechanisms of the IP process and is fundamental for exploring high-performance desalination membranes.

An exclusive kinetics of long chain fatty alcohol oxidation administered by CMC in anionic micellar media and in their binary mixture

This work thrives an organic oxidative transformation of long chain fatty alcohol, decanol, by hexavalent chromium in anionic micellar assisted aqueous medium at 25 °C. The spectrophotometrically studied kinetics of the oxidation has been recorded in a comparative mode in single and mixed micellar media of anionic surfactants (SDSʹ and SDS) of varying chain length. Moreover, another unprecedented comparative kinetic study of promoted (Phen and Bpy promoters) and unpromoted reactions has been shown in both the micellar system. A direct connection of reaction rate with CMC of the surfactants has been shown here. Some necessary spectral analyses (IR and 1H NMR) have been carried out to elucidate the product formation.

Wormlike reverse micelles loaded with aqueous extracts of Psidium guajava leaves: Performance evaluation by rheology and Raman microscopy methods

Phenolic compounds are molecules that provide health benefits. However, they present problems for their use. The use of wormlike reverse micelles to load aqueous extracts of Psidium guajava (guava) was carried out. Different solutions (i.e., content variation of canola oil, oleic acid, soy lecithin; stirring time, stirring speed) were obtained by incorporation of water by ultrasound and centrifugation. The behavior of the wormlike micelles was evaluated with optical microscopy, simple shear tests, and Raman microscopy with and without aqueous extract of guava leaves. The wormlike reverse micelles solution were adjusted to the Carreau-Yasuda model. Influence of the aqueous extracts of guava leaves were observed in the parameters of Carreau-Yasuda model, related with changes in the packing of the hydroxyl groups and high order of packing in wormlike reverse micellar system.

Radiolabelled folate micellar carriers as proposed diagnostic aid for CNS tumors by nasal route.

Glioma refers to the most atypical variant of the malignant central nervous system tumors posturing massive challenge to the research fraternity owing to the flimsy improvement in the patient survival rate over the past years. The aim of the proposed work was developing a diagnostic aid for brain tumors, which could be administered via the non-invasive intranasal route. Since overexpression of folate receptors in the central nervous system tumors is 500 times more than the normal healthy cells, we aimed at fabricating a radiolabeled folate encapsulated micellar delivery system to be given via the nasal route. Folate conjugated bifunctional chelating agent was synthesized, radiolabeled with 99mTc, and encapsulated in a micellar carrier. The fabricated micelles were further evaluated for in vivo nasal toxicity in rats and the same were found safe for intranasal administration. The fabricated micelles owing to their nano size, mucoadhesive nature, and enhanced permeation were observed to have a higher uptake into the brain (around 16% in 4 h) than as compared to the radiolabeled conjugated folate solution when studied for in vivo biodistribution in mice. Single-photon emission computerized tomography imaging performed in higher animals upon intranasal administration of the micellar formulation revealed enhanced uptake of the micelles into the animal brain. It is believed that the aforementioned formulation can be of a great diagnostic value in the detection of not only brain tumors but also other folate expressing cancers such as cervical, breast, and lungs as the system is fast, non-toxic, accurate, non-invasive, and simple.

Double-Loaded Doxorubicin/Resveratrol Polymeric Micelles Providing Low Toxicity on Cardiac Cells and Enhanced Cytotoxicity on Lymphoma Cells.

The anthracycline antibiotic doxorubicin is a well-known antitumour agent, however its cardiotoxicity is a significant obstacle to therapy. The aim of the present study was to improve the safety of doxorubicin through its simultaneous encapsulation with a cardioprotective agent (resveratrol) in Pluronic micelles. The formation and double-loading of the micelles was performed via the film hydration method. Infrared spectroscopy proved the successful incorporation of both drugs. X-ray diffraction analyses revealed that resveratrol was loaded in the core, whereas doxorubicin was included in the shell. The double-loaded micelles were characterised by a small diameter (26 nm) and narrow size distribution, which is beneficial for enhanced permeability and retention effects. The in vitro dissolution tests showed that the release of doxorubicin depended on the pH of the medium and was faster than that of resveratrol. In vitro studies on cardioblasts showed the opportunity to reduce the cytotoxicity of doxorubicin through the presence of resveratrol in double-loaded micelles. Higher cardioprotection was observed when the cells were treated with the double-loaded micelles compared with referent solutions with equal concentrations of both drugs. In parallel, treatments of L5178 lymphoma cells with the double-loaded micelles revealed that the cytotoxic effect of doxorubicin was enhanced. Thus, the study demonstrated that the simultaneous delivery of doxorubicin and resveratrol via the micellar system enabled the cytotoxicity of doxorubicin in lymphoma cells and lowered its cardiotoxicity in cardiac cells.

Unveiling the Transformation from Aggregation‐Caused Quenching to Encapsulation‐Induced Emission Enhancement for Improving the Photoluminescence Properties and Detection Performance of Conjugated Polymer Material in Multiple States

AbstractHigh hydrophobicity of π‐extended conjugated polymers (CPs) adversely affects their photoluminescence quantum yield (PLQY) in water and hydrogel/solid state via an unsolicited aggregation‐caused quenching (ACQ) process which ultimately hampers their sensing and imaging performance. Herein, an efficient strategy is presented to suppress and transform such ACQ process into an encapsulation‐induced emission enhancement (EIEE) effect through facile preparation of CP/Pluronic F‐127 fluorescent hybrid micelles and hydrogel. As a proof‐of‐concept, successful encapsulation of polyfluorene derivative PF‐DBT‐Im into F‐127 micelles not only displays an improved PLQY (≈200% increment) in water/hydrogel state but also delivers unique and augmented sensing responses toward the emerging pollutants tetracyclines taken as model analyte, validating the superiority of EIEE‐active hybrid micellar systems over ACQ suffering PF‐DBT‐Im aggregates. The established method not only provides a facile solution to circumvent ACQ problem existing in low water dispersible CPs but also endorses an enhanced, simplified sensing system for visual and on‐site detection of analytes with likely futuristic applications in biomedicine and solid‐state optoelectronics.

Ciprofloxacin-Loaded Mixed Polymeric Micelles as Antibiofilm Agents.

In this work, mixed polymeric micelles (MPMs) based on a cationic poly(2-(dimethylamino)ethyl methacrylate)-b-poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA29-b-PCL70-b-PDMAEMA29) and a non-ionic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO99-b-PPO67-b-PEO99) triblock copolymers, blended at different molar ratios, were developed. The key physicochemical parameters of MPMs, including size, size distribution, and critical micellar concentration (CMC), were evaluated. The resulting MPMs are nanoscopic with a hydrodynamic diameter of around 35 nm, and the ζ-potential and CMC values strongly depend on the MPM's composition. Ciprofloxacin (CF) was solubilized by the micelles via hydrophobic interaction with the micellar core and electrostatic interaction between the polycationic blocks, and the drug localized it, to some extent, in the micellar corona. The effect of a polymer-to-drug mass ratio on the drug-loading content (DLC) and encapsulation efficiency (EE) of MPMs was assessed. MPMs prepared at a polymer-to-drug mass ratio of 10:1 exhibited very high EE and a prolonged release profile. All micellar systems demonstrated their capability to detach pre-formed Gram-positive and Gram-negative bacterial biofilms and significantly reduced their biomass. The metabolic activity of the biofilm was strongly suppressed by the CF-loaded MPMs indicating the successful drug delivery and release. The cytotoxicity of empty and CF-loaded MPMs was evaluated. The test reveals composition-dependent cell viability without cell destruction or morphological signs of cell death.

Smart pH- and Temperature-Sensitive Micelles Based on Chitosan Grafted with Fatty Acids to Increase the Efficiency and Selectivity of Doxorubicin and Its Adjuvant Regarding the Tumor Cells.

The main factors that determine the low effectiveness of chemotherapy are the low target bioavailability of antitumor drugs and the efflux process. In attempts to overcome this problem, several approaches are proposed here. Firstly, the development of polymeric micellar systems based on chitosan grafted by fatty acids (different types to optimize their properties), which, on the one hand, increase the solubility and bioavailability of cytostatics and, on the other hand, effectively interact with tumor cells due to the polycationic properties of chitosan, allowing for more effective penetration of cytostatic drugs into the cells. Secondly, the use of adjuvants-synergists of cytostatics (such as eugenol) included in the same micellar formulation-that selectively enhance the accumulation and retention of cytostatics in the tumor cells. pH- and temperature-sensitive polymeric micelles developed show high entrapment efficiency for both cytostatics and eugenol (EG) >60% and release the drug in a prolonged manner for 40 h in a weakly acidic medium corresponding to the microenvironment of tumors. In a slightly alkaline environment, the drug circulates longer (more than 60 h). The thermal sensitivity of micelles is realized due to an increase in the molecular mobility of chitosan, which undergoes a phase transition at 32-37 °C. The effect of the cytostatic drug doxorubicin (Dox) on cancerous A549 cells and model healthy cells of human embryonic renal epithelium (HEK293T) was studied by FTIR spectroscopy and fluorescence microscopy. Micellar Dox penetrates into cancer cells 2-3 times more efficiently when using EG adjuvant, which inhibits efflux, as demonstrated by a significant increase in the ratio of intra- and extracellular concentrations of the cytostatic. However, here it is worth remembering about healthy cells that they should not be damaged: according to changes in the FTIR and fluorescence spectra, the penetration of Dox into HEK293T when using micelles in combination with EG is reduced by 20-30% compared to a simple cytostatic. Thus, experimental developments of combined micellar cytostatic drugs have been proposed to increase the effectiveness of cancer treatment and overcome multiple drug resistance.

Development of a Sensitive and Selective Method for the Determination of some Selected Aldehydes Based on Fluorescence Quenching.

Phenanthrene fluorescence quenching in anionic micellar system of sodium dodecyl sulphate (SDS) was explored for the development of a sensitive and selective method for a group of selected aldehydes (2,6-dichlorobenzaldehyde, 4-(dimethylamino)benzaldehyde, 4-aminobenzaldehyde, 4-nitrobenzaldehyde, 2-chlorobenzaldehyde, benzaldehyde and 2-methoxybenzaldehyde). Experiments were performed in 0.02mol L- 1 SDS. All the studied aldehydes quenched the fluorescence intensity of the probe (phenanthrene). Stern-Volmer equation was useful in explaining the phenanthrene quenching by the studied aldehydes. Stern-Volmer constants ([Formula: see text]) were obtained as a result of using the Stern-Volmer equation that gives the information in respect of sensitivity of the method for the studied aldehydes. Greater the [Formula: see text] higher will be the sensitivity and vice versa. [Formula: see text], detection limit (DL) and quantification limit (QL) were observed in the order 2,6-dichlorobenzaldehyde > 4-dimethylaminobenzaldehyde > 4-aminobenzaldehyde > 4-nitrobenzaldehyde > 2-chlorobenzaldehyde > benzaldehyde > 2-methoxybenzaldehyde. Phenanthrene fluorescence quenching by the studied aldehydes is useful for their determination in environmental samples.