Micelle Swelling Research Articles

Casein and acryl amide complexation and bio-adhesive polymeric nano micelles influence on vortioxetine dissolution, penetration enhancement and in vivo absorption

Vortioxetine (VTX) is a new atypical antidepressant used to treat major depression and other mental disorders. Due to its low water solubility, oral absorption, and fast metabolism, VTX has been commercially manufactured and sold as a hydrobromide. Long-term VTX hydrobromide therapy is frequently associated with respiratory irritation and digestive dysfunction. Two techniques were developed for dissolution, swelling, adherence, and penetration enhancements. The techniques were the VTX and casein (CAS) complexation using the maximum loading capacity, and VTX-polymeric nano micelle using the “Sandwich Technique”. This study includes the maximum VTX-CAS binding capacity determination, VTX-CAS complex preparation, polymeric nano micelle encapsulating VTX-CAS complex optimizations, physiochemical characterisations, solubility assessment, VTX release analysis, swelling analysis and mucus-penetrating study of the VTX-CAS complex and VTX polymeric nano micelle in comparison to the VTX raw material. The optimum VTX-polymeric nano micelle dissolution, swelling, adherence, and penetration enhancements were supported by the results of 91.10±16.34 nm, +19 mV zeta-potential, structural arrangements, and enhanced amorphic character with the morphology and size distribution (50–100 nm). The VTX-polymeric nano micelle could serve as an oral alternative to the VTX hydrobromide therapy based on the results of the biocompatibility and in vivo absorption studies for the VTX-polymeric nano micellar system.

A Stochastic FRET Study on the Core Dimension of Polystyrene-block-Poly(Polyethylene Glycol Monomethyl Ether Acrylate) Micelles.

Polystyrene-b-poly(polyethylene glycol monomethyl ether acrylate) (PSt-b-PPEGA) copolymers featuring pyrene and perylene as the Förster resonance energy transfer (FRET) donor (denoted as D-BCP) and acceptor (denoted as A-BCP), respectively, were synthesized via the reversible addition and fragmentation chain transfer (RAFT) polymerization. These copolymers were then used to form DA-mixed micelles via a dialysis method. The micelles consisted of D-BCP (mole fraction fD = 0.04), A-BCP (fA = 0.04), and label-free PSt-b-PPEGA (fN = 0.92). The decrease in fluorescence intensity of pyrene in the micelles confirmed the occurrence of FRET, with an observed efficiency of 0.32. A Monte Carlo approach was employed to estimate the expected FRET efficiency, assuming the random fractional distribution of D-BCP and A-BCP, along with the random spatial distribution of pyrene and perylene within the micellar core. The observed FRET efficiency suggested a core radius (Rc) of 0.95R0, where R0 was the Förster critical distance. With R0 calculated to be 3.2 nm based on Förster theory, Rc was determined to be approximately 3.0 nm, aligning closely with the dried-out core radius estimated from aggregation number and polystyrene density. This stochastic FRET methodology was further applied to investigate the swelling behavior of the polymer micelles in a mixture of N,N-dimethylformamide (DMF) and water. Dynamic light scattering analysis revealed minimal change in core dimension below 60 vol % DMF content. However, FRET analysis provided a deeper insight, showing an increase in core radius with DMF content up to 20 vol %, followed by saturation up to 50 vol %, offering a more comprehensive understanding of the micelle swelling behavior.

3D Superstructures Consisting of Intersecting Gold Lamellae Formed by a Micelle‐Mediated Anisotropic Growth Approach

3D superstructures (3DSs) have attracted increasing interest because of the collective synergistic effects of individual building units, but their customization relies on tedious multistep strategy or high‐end nanofabrication technology. Herein, for the first time, a facile block copolymer micelle‐mediated anisotropic growth approach is reported to fabricate gold 3DSs consisting of tunable and intersecting lamellae with sawtooth‐like edges. The preparation of the 3DSs depends on the mediation of reduction kinetics of gold precursors and adsorption of block copolymer micelles on gold crystal surfaces using disulfiram as ligands. The thickness of lamellae in the 3DSs is controllable from ≈21 to 102 nm by adjusting the weight fraction of the micellar hydrophobicity blocks and the composed lamellar number is regulated from ≈3 to ≈30. Additional morphologies, such as a dendritic mesoporous structure and meatball‐like shapes, are obtained through controlling the extent of micelle swelling. Finite‐difference time‐domain simulations demonstrate that the unique 3DSs of gold lamellae with sawtooth‐like edges form abundant hotspots giving rise to surface‐enhanced Raman scattering (SERS). The 3DSs exhibit strong electromagnetic field enhancement and excellent performance as SERS substrates for detecting 4‐mercaptobenzoic acid.

Macromolecular NO-Donor Micelles for Targeted and Augmented Chemotherapy against Prostate Cancer.

Mitoxantrone (MTO) is clinically utilized for treating hormone-refractory prostate cancer (PCa), however, the therapeutic outcome is far from optimal due to the lack of proper drug carrier as well as the inherent MTO detoxification mechanisms of DNA lesion repair and anti-oxidation. Herein, a bombesin-installed nanoplatform combining the chemotherapeutic MTO and the chemotherapeutic sensitizer of nitric oxide (NO) is developed based on MTO-loaded macromolecular NO-donor-containing polymeric micelles (BN-NMMTO ) for targeted NO-sensitized chemotherapy against PCa. BN-NMMTO actively target and accumulates in PCa sites and are internalized into the tumor cells. The macromolecular NO-donor of BN-NMMTO undergoes a reductive reaction to unleash NO upon intracellular glutathione (GSH), accompanying by micelle swelling and MTO release. The targeted intracellular MTO release induces DNA lesion and reactive oxygen species (ROS) generation in tumor cells without damage to the normal cells, and MTO's cytotoxicity is further augmented by NO release via the inhibition of both DNA repair and anti-oxidation pathways as compared with traditional MTO therapies.

Structural changes in fasted state dietary mixed micelles upon solubilization of beta-carotene

It was aimed to investigate the structural changes taking place in duodenal mixed micelles (MM) at fasted state with the incorporation of fatty acids (FA) and the morphological transformations in these MMs upon solubilization of β-carotene (BCR) through coarse-grained (CG) molecular dynamics (MD) simulations. All simulations were performed with GROMACS 2019 simulation package using the Martini force field. Lauric acid (LA), stearic acid (SA) and linoleic acid (LNA) were used to explore the effects of FA chain length and unsaturation. Micelle swelling was observed with the incorporation of all FAs. The increase in size was in line with increasing FA chain length and unsaturation. MMs incorporating LA and SA were ellipsoidal in shape, while polyunsaturated LNA resulted in a worm-like MM. Upon solubilization of BCRs, swelling was observed only in the MMs with long-chain SA and LNA. No micelle growth was observed in the plain and LA MMs despite their smaller sizes. This was attributed to their low-density hydrophobic cores, which allowed a condensation effect induced by the interactions between BCRs and POPC tails. It is inferred that when the micelle is large enough to solubilize BCRs, whether or not swelling will take place depends on the core density. The increase in micelle size was very small in the MM incorporating LNA compared to that in the MM with SA, which was accompanied by an elliptical-to-cylindrical shape transformation. This was due to the fluid nature of the worm-like LNA micelle, which readily allowed the solubilization of 3 BCRs within its core. By resolving the internal structures of BCR incorporated MMs, this study gives valuable insight into the effects of FA chain length and unsaturation on the solubilization behavior of dietary MMs. The results are expected to give direction to the development of rational design strategies for effective BCR delivery systems.

Spontaneous Emulsions: Adjusting Spontaneity and Phase Behavior by Hydrophilic-Lipophilic Difference-Guided Surfactant, Salt, and Oil Selection.

Spontaneous emulsion behavior has been difficult to predict and could be influenced by many variables including salinity, temperature, and chemical composition of the oil and surfactant. In this work, the hydrophilic-lipophilic difference (HLD) framework was used to predict the formation of spontaneous emulsions using a mixture of Span-80 and SLES surfactants. The spontaneity and emulsion behavior of different systems were modeled by estimating the HLDmix. The influence of surfactant ratio, salinity, and oil type was investigated. Spontaneous emulsification could only be observed when the HLDmix was between -0.96 and 1.04. Within this range, a negative HLDmix resulted in a greater spontaneity to form o/w emulsion, and a w/o emulsion was more likely to form when the HLDmix was positive. When the HLDmix was close to 0 (between -0.22 and 0.56 in our systems), emulsions were formed in both the oil and aqueous phases with high spontaneity. A combined effect of ultralow interfacial tension, Span-80 micelle swelling, and interfacial turbulence due to Marangoni effects is likely the main mechanism of the spontaneous emulsification observed in this study. A synergistic reduction in interfacial tension was observed between Span-80 and SLES (<1 mN/m). When the HLD of the system was close to 0, a bicontinuous emulsion phase was formed at the oil-water interface. The bicontinuous emulsion broke-up over time due to the ultralow interfacial tension and interfacial turbulence, forming dispersed oil and water droplets. Results from this work provide a practical method to suggest what surfactant composition, salinity, and oil type could promote (or eliminate) the conditions favorable for spontaneous emulsification.

Complex pH-Dependent Interactions between Weak Polyelectrolyte Block Copolymer Micelles and Molecular Fluorophores.

Amphiphilic block copolymers with weak polyelectrolyte blocks can assemble stimulus-responsive nanostructures and interfaces. Applications of these materials in drug delivery, biomimetics, and sensing largely rely on the well-understood swelling of polyelectrolyte chains upon deprotonation, often induced by changes in pH or ionic strength. This deprotonation can also tune interfacial interactions between the polyelectrolyte blocks and surrounding solution, an effect which is less studied than morphological swelling of polyelectrolytes but can be just as critical for intended function. Here, we investigate whether the pH-driven morphological response of polyelectrolyte-bearing nanostructures also affects the interactions of these nanostructures with molecules in solution, using micelles of a short-chain polybutadiene-block-poly(acrylic acid) (pBd-pAA) as a model system. We introduce a Förster resonance energy transfer (FRET) approach to probe interactions between micelles and fluorescent molecular solutes as a function of solution pH. As expected, the pAA corona of these pBd-pAA micelles increases in thickness monotonically as a function of pH. However, FRET efficiency, which provides a metric of the spatial proximity of fluorescently labeled micelles and freely diffusing fluorophores, exhibits complex nonmonotonic behavior as a function of pH, indicating that the average separation of micelles and acceptor fluorophores is not strictly correlated with micelle swelling. Dialysis experiments quantify the affinity of fluorophores for micelles as a function of pH, confirming that changes in FRET are driven almost entirely by the pH-dependent affinity of the pAA block for the investigated molecular fluorophores, not simply by a shape change of the pAA corona. This study provides key insights into the interfacial interactions between weak-polyelectrolyte-bearing nanostructures and molecular solutes, of importance for the development of their stimulus-responsive applications.

Macroporous chitin microspheres prepared by surfactant micelle swelling strategy for rapid capture of lead (II) from wastewater

Heavy metal pollution of water source continues to be one of the most serious environmental problems which have attracted major global concern. Here, a macroporous chitin microsphere is prepared by surfactant micelle swelling strategy followed by modification with tetraethylenepentamine for Pb2+ removal from wastewater. The resultant adsorbent not only exhibits fast adsorption kinetic (>80% of its equilibrium uptake within 20 min) but also has high adsorption capacity of 218.4 ± 6.59 mg/g and excellent reusability (>75% of its initial adsorption capacity after five adsorption/desorption cycles). More importantly, under the continuous operating mode, the adsorbent can treat about 39,000 kg water/kg adsorbent, and the Pb2+ concentration decreases from 2000 μg/L to smaller than 10 μg/L, meeting the drinking water standard recommended by the World Health Organization (10 μg/L). All results indicate that the tetraethylenepentamine-modified macroporous chitin microspheres have great potential in the treatment of heavy metal contamination.

Toluidine blue-immobilized macroporous chitosan microspheres for highly efficient purification of fucoidan

Advanced adsorbents offer possible solutions to the challenge of isolation and purification of fucoidan. In this work, a toluidine blue-immobilized macroporous chitosan microsphere (TMCM) is prepared by surfactant micelle swelling strategy followed by modification with toluidine blue for efficiently purification of fucoidan. The macroporous structure of TMCM provides wide channels and allows fast mass transfer of adsorbates, thereby affording fast adsorption rate and high desorption efficiency; Toluidine blue, a high-affinity ligand that is immobilized on the pore surface, renders high adsorption capacity and selectivity for fucoidan. Adsorption experiments demonstrated that TMCM has superior adsorption performances, including fast adsorption rate with the adsorption amount 164.10 mg/g within 15 h, high desorption efficiency with over 93.6%, high adsorption capacity with 187.69 mg/g, and good selectivity, indicating a very appealing application prospect.

Predicting Spontaneous Emulsification in Saltwater Environments Using the HLD Model.

Spontaneous emulsification of toluene with nonylphenol polyethoxylate (NPE) and sodium dodecylbenzenesulfonate (SDBS) surfactants in saltwater environments was studied. NaCl promoted the spontaneous emulsification of an otherwise non-spontaneous SDBS-toluene system. Dynamic light scattering and turbidity indicated that spontaneity increased with NaCl concentration. The mechanism of spontaneous emulsification was dependent on surfactant type; NPE emulsified via micelle swelling, and SDBS emulsified via nucleation and growth. Hydrophilic lipophilic difference (HLD) calculations were used to model spontaneous emulsification and spontaneity. As HLD approached zero, conditions became more favorable for spontaneous emulsification. Between HLD values of -2.4 and -2.05, samples transitioned from non-spontaneous to spontaneous. This study aids in predicting spontaneous emulsion formation in saltwater environments for applications in nanoemulsion formation and wastewater remediation.

Macroporous cellulose/carbon nanotube microspheres prepared by surfactant micelle swelling strategy for rapid and high-capacity adsorption of bilirubin

It remains a formidable challenge to construct high-performance haemoperfusion adsorbents with fast adsorption kinetic and high adsorption capacity for efficiently removing bilirubin from human blood. In this work, we report a facile yet efficient strategy to manufacture lysine-modified macroporous cellulose/carbon nanotube microspheres (LMCMs) by surfactant micelles swelling strategy followed by modification with lysine. The macroporous structure not only provides wide channels for fast mass transfer, but also shortens the diffusion path into meso/micropores, increasing the accessibility of mesopores and micropores. Experimental results reveal that LMCMs can remove bilirubin with fast adsorption kinetic (> 90% of its equilibrium uptake within 2 h) and high adsorption capacity of 338.14 mg/g. More importantly, the adsorbent can remove about 79% of bilirubin in rabbit serum, and the bilirubin concentration in rabbit serum decreases from 213.36 to 45.78 mg/L within 2 h, indicating a very appealing application prospect.

(Invited) Synthesis and Optical Properties of Core-Shell Swnt Hybrids

Because of their emission in the near infrared region, Single-Walled Carbon Nanotubes remain among the most attractive nanomaterials for (opto)electronics, optics and photonics.1 - 3 However, the extreme sensitivity of nanotubes to their environment hinders their applications. Thus, the fabrication of tailor-made functional hybrid materials that preserve the optical properties of SWNTs and facilitate their manipulation is extremely important. One route to take advantage of the protection offered by polymers is to synthesize core/shell nanostructures in which the nanotube is the active core and the polymer, tightly bound to the nanotubes, acts as a protective shell.Here, we describe the synthesis of core-shell nanotube materials made of SWNTs and polystyrene. We developed a two-step strategy that permits to form a stable and homogeneous layer of polymer around the nanotubes by adding first polystyrene via the micelle swelling method and then by locking the structure via radical polymerisation in micelles of styrene and divinylbenzene. After polymerisation and redispersion, the nanotube hybrids can be easily manipulated in solution; they still exhibited photoluminescence properties both in solution and in the solid state demonstrating that the SWNTs embedded in their polystyrene shell are isolated one from each other.4 ,5 References Avouris, P.; Freitag, M.; Perebeinos, V. Nat. Photonics 2008, 2, 341-350.Godin, A. G.; Varela, J. A.; Gao, Z.; Danné, N.; Dupuis, J. P.; Lounis, B.; Groc, L.; Cognet, L. Nat. Nanotechnol. 2017, 12, 238-243.He, X.; Htoon, H.; Doorn, S. K.; Pernice, W. H. P.; Pyatkov, F.; Krupke, R.; Jeantet, A.; Chassagneux, Y.; Voisin, C. Nat. Mater. 2018, 17, 663-670.Orcin-Chaix, L.; Trippé-Allard, G.; Voisin, C.; Okuno, H.; Derycke, V.; Lauret, J.-S.; Campidelli, S. J. Mater. Chem. C 2018, 6, 4786-4792.Orcin-Chaix, L.; Campidelli, S.; Rondin, L.; Fossard, F.; Bretenaker, F.; Chassagneux, Y.; Voisin, C.; Lauret, J.-S. ACS Appl. Nano Mater. 2020, 3, 7291-7296 Figure 1

Rapid removal of rhodamine dye from aqueous solution using casein-surfactant complexes: role of casein-surfactant interaction

We report here a new approach to remove rhodamine B dye, a toxic contaminant in industrial effluents, from aqueous solution using colloidal casein protein and its complexes with surfactants. The dye removal efficiency of casein is studied in the absence and in the presence of anionic, cationic, and nonionic surfactants. The anionic, cationic, and nonionic surfactants used in this study are sodium dodecyl sulfate (SDS), cetyltrimethylammonium bromide (CTAB), and Triton X-100, respectively. The presence of Triton X-100 is found to improve the dye removal efficiency of casein from 21 to 84% with a contact time of 5 minutes. The effect of contact time, pH, and temperature on the dye removal efficiency of casein is also studied here. The adsorption of rhodamine B on casein micelles is found to follow the Freundlich adsorption isotherm and a pseudo second order kinetics model. The variation in hydrodynamic diameter of casein in whole and skimmed milk exhibited similar trend for a given surfactant at different concentrations, which suggests that the presence of fat globules, does not interfere with the interaction of casein for a given surfactant. The hydrodynamic diameter of casein micelles in reconstituted aqueous casein solution is found to increase with an increase in the concentration of SDS, which is attributed to the interaction of SDS with micelles at calcium phosphate sequestration centers, which results in micelle swelling. In the presence of CTAB at varying concentration, the diameter of casein micelles in reconstituted aqueous casein is found to decrease. This is attributed to the interaction of cationic group of CTAB with negatively charged κ-casein which makes the micelles more compact as a result of reduced electrostatic repulsion between the micelles. Similarly, the hydrodynamic diameter of casein micelles in reconstituted casein containing varying concentrations of Triton X-100 is found to decrease which suggests that large micelles break down into smaller micelles. Thus, this work gives new insights to the interaction of casein with anionic, cationic, and nonionic surfactants when present in whole milk, skimmed milk, and reconstituted aqueous solution. Further, casein-Triton X-100 complexes are found to effectively remove rhodamine B dye rapidly due to the synergistic interaction between casein, rhodamine B, and Triton X-100.

An experimental investigation on ballistic efficiency of silica-based crosslinked aerogels in aramid fabric

The ballistic performance of crosslinked aerogels which were synthesized using a micelle swelling and structure directing agent against Level IIIA threat was experimentally investigated in this study. Firstly, silica-based aerogels were synthesized in a small scale, and then, isocyanate crosslinking was applied to them. According to the characterization results, the best sample with a desired pore structure for energy absorption was determined. Then, scale-up manufacturing was realized for this sample to use in ballistic tests. Subsequently, neat aramid fabrics with different numbers of layers were tested, and back-face deflection values were determined. The neat aramid fabrics with 24, 30 and 36 layers were deflected as 57.32, 43.58 and 40.38 mm, respectively. To understand the efficiency of the crosslinked aerogel sample, it was placed into the 30 layers of the aramid fabric as the back-face deflection value of its neat form was closest to the critical back face deflection value which is defined in the related standard. Three types of aerogel monoliths, as rectangular, large diameter of circular and small diameter of circular were tested with aramid fabrics. Fewer fabrics were perforated at the rate of 72% in all ballistic test samples including aerogel monoliths in comparison to the neat aramid fabric tests. 7 or 8 layers of fabric were perforated in the test of the neat aramid fabric samples, while 2 layers of fabric were perforated in the samples containing aerogel.

Diffusion-Controlled Spontaneous Emulsification of Water-Soluble Oils via Micelle Swelling.

Spontaneous emulsification of toluene, xylenes, cyclohexane, and mineral oil in a nonionic nonylphenol polyethoxylate surfactant solution was investigated by visual observations coupled with dynamic light scatting measurements and interfacial tensiometry. For water-soluble oils, nanoscale emulsions formed spontaneously by diffusion of oil molecules into the aqueous surfactant solutions and subsequent swelling of surfactant micelles with oil. Micelle swelling rates were quantified to assess system spontaneity, revealing that oil solubility in water was directly correlated to the spontaneity of the emulsion (toluene > xylenes > cyclohexane). When experiments were intentionally designed to create surfactant concentration gradients, Marangoni flows were found to enhance spontaneity. Despite their spontaneous formation, emulsion stability was limited over the course of 40 days by Ostwald ripening followed by creaming and evaporation. These results provide insights on the likelihood of nanoemulsion formation and persistence in oily wastewater as the components in this study are present in many wastewater systems.

Permeability of Ciprofloxacin-Loaded Polymeric Micelles Including Ginsenoside as P-glycoprotein Inhibitor through a Caco-2 Cells Monolayer as an Intestinal Absorption Model.

The low oral bioavailability of ciprofloxacin is associated with two distinct challenges: its low aqueous solubility and efflux by p-glycoproteins (P-gp) in the intestinal membrane. Several studies were conducted in order to improve its solubility and permeability through the gastrointestinal membrane. In this study, in a full factorial design study, eight polymeric micelles were prepared and their characteristics, including particle size, loading and release rate were evaluated. Polymeric micelles demonstrated particle sizes below 190 nm and 27–88% loading efficiency. Drug release was affected by drug solubility, polymeric micelle erosion and swelling in simulated gastrointestinal fluids. An optimized polymeric micelle was prepared based on appropriate characteristics such as high drug loading and low particle size; and was used for a permeation study on Caco-2 cells. Optimized polymeric micelles with and without ginsenoside and ginsenoside alone enhanced drug permeability through Caco-2 cells significantly in the absorptive direction. The effect of ginsenoside was dose dependent and the maximum effect was seen in 0.23 mg/mL concentration. Results showed that P-gp may not be responsible for ciprofloxacin secretion into the gut. The main mechanism of ciprofloxacin transport through Caco-2 cells in both directions is active diffusion and P-gp has inhibitory effects on ciprofloxacin permeability in the absorptive direction that was blocked by ginsenoside and micelles without ginsenoside.

Dipole-switch induced modification of the emissive response of carbon nanotubes

The interaction of carbon nanotubes with the molecular dipole switch spiropyran is expected to affect the optical response of the tubes. Until now, the need of anchor groups to immobilize the switches on the tubes has hindered the experimental observation of the effects of switching on the emission behavior of the tubes. Here we present spiropyran-carbon nanotube complexes obtained by micelle swelling. This method does not require any anchor nor sophisticated chemistry to warrant close tube-switch proximity. For the first time, we observe the shifts predicted theoretically and their effect on the tubes’ excitation and emission energies.

Spin‐labeling of polymeric micelles and application in probing micelle swelling using EPR spectroscopy

ABSTRACTPolymer structure and conformational dynamics are essential to polymer macroscopic properties, but are challenging to probe. We report here a synthetic pathway to chemically add a nitroxide moiety onto block polymers in a mild, aqueous environment and demonstrate its use in a series of polymeric micelles using Electron Paramagnetic Resonance (EPR) spectroscopy. The micelles were characterized with several analytical approaches and EPR findings were in general consistent with other approaches. Upon exposure to organic solvents, the line shape changes reflected the micelle swelling and EPR spectral simulations revealed structural information of the swelled micelles. The label introduced via our method can be cleaved and replaced with other probes to report different information site‐specifically. The mild conditions facilitate the future use of EPR in solving biopolymer problems. In combination with other labeling approaches, one can perform polymer spin labeling with different chemistry, so that various information about polymers can be obtained site‐specifically. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1770–1782

Effects of calcium chelating agents on the solubility of milk protein concentrate

The aim of this study was to determine the effects of calcium chelating agents on the dissolution and functionality of 10% (w/w) milk protein concentrate (MPC) powder. MPC powder dissolution rate and solubility significantly (P &gt; 0.05) increased with addition of sodium phosphate, trisodium citrate (TSC) and sodium hexametaphosphate (SHMP), compared to MPC dispersions alone. Trisodium citrate and SHMP addition increased viscosity as a result of micelle swelling. However, dispersions containing SHMP showed a decrease in viscosity after prolonged time due to micelle dissociation. Overall, MPC powder dissolution was aided by the addition of calcium chelating agents.

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles

β-casein is an amphiphilic protein that self-organizes into well-defined core–shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration.