Micellar Nanostructures Research Articles

Corannulene: A Curved Polyarene Building Block for the Construction of Functional Materials.

This Account describes a body of research in the design and synthesis of molecular materials prepared from corannulene. Corannulene (C20H10) is a molecular bowl of carbon that can be visualized as the hydrogen-terminated cap of buckminsterfullerene. Due to this structural resemblance, it is often referred to as a buckybowl. The bowl can invert, accept electrons, and form host-guest complexes. Due to these characteristics, corannulene presents a useful building block in materials chemistry.In macromolecular science, for example, assembly of amphiphilic copolymers carrying a hydrophobic corannulene block enables micelle formation in water. Such micellar nanostructures can host large amounts of fullerenes (C60 and C70) in their corannulene-rich core through complementarity of the curved π-surfaces. Covalent stabilization of the assembled structures then leads to the formation of robust water-soluble fullerene nanoparticles. Alternatively, use of corannulene in a polymer backbone allows for the preparation of electronic and redox-active materials. Finally, a corannulene core enables polymer chains to respond to solution temperature changes and form macroscopic fibrillar structures. In this way, the corannulene motif brings a variety of properties to the polymeric materials.In the design of non-fullerene electron acceptors, corannulene is emerging as a promising aromatic scaffold. In this regard, placement of sulfur atoms along the rim can cause an anodic shift in the molecular reduction potential. Oxidation of the sulfur atoms can further enhance this shift. Thus, a variation in the number, placement, and oxidation state of the sulfur atoms can create electron acceptors of tunable and high strengths. An advantage of this molecular design is that material solubility can also be tuned. For example, water-soluble electron acceptors can be created and are shown to improve the moisture resistance of perovskite solar cells.Host-guest complexation between corannulene and γ-cyclodextrin under flow conditions of a microfluidic chamber allows for the preparation of water-soluble nanoparticles. Due to an oligosaccharide-based sugarcoat, the nanoparticles are biocompatible while the corannulene component renders them active toward nonlinear absorption and emission properties. Together, these attributes allow the nanoparticles to be used as two-photon imaging probes in cancer cells.Finally, aromatic extension of the corannulene nucleus is seen as a potential route to nonplanar nanographenes. Typically, such endeavors rely upon gas-phase synthesis or metal-catalyzed coupling protocols. Recently, two new approaches have been established in this regard. Photochemically induced oxidative cyclization, the Mallory reaction, is shown to be a general method to access corannulenes with an extended π-framework. Alternatively, solid-state ball milling can achieve this goal in a highly efficient manner. These new protocols bring practicality and sustainability to the rapidly growing area of corannulene-based nanographenes.In essence, corannulene presents a unique building block in the construction of functional materials. In this Account, we trace our own efforts in the field and point toward the challenges and future prospects of this area of research.

Shape-Changing Bottlebrush Polymers.

Bottlebrush polymers (BBPs), composed of relatively short polymeric side chains densely grafted on a polymer backbone, exhibit many unique characteristics and hold promise for a variety of applications. This Perspective focuses on environmentally induced shape-changing behavior of BBPs at interface and in solution, particularly worm/star-globule shape transitions. While BBPs with a single type of homopolymer or random copolymer side chains have been shown to undergo pronounced worm-to-globule shape changes in response to external stimuli, the collapsed brushes are unstable and prone to aggregation. By introducing a second, solvophilic polymer into the side chains, either as a distinct type of side chain or as the outer block of block copolymer side chains, the collapsed brushes not only are stabilized but also create unimolecular micellar nanostructures, which can be used for, e.g., encapsulation and delivery of substances. The current challenges in the design, synthesis, and characterization of stimuli-responsive shape-changing BBPs are discussed.

Förster Resonance Energy Transfer Nanoplatform Based on Recognition-Induced Fusion/Fission of DNA Mixed Micelles for Nucleic Acid Sensing.

The dynamic nature of micellar nanostructures is employed to form a self-assembled Förster resonance energy transfer (FRET) nanoplatform for enhanced sensing of DNA. The platform consists of lipid oligonucleotide FRET probes incorporated into micellar scaffolds, where single recognition events result in fusion and fission of DNA mixed micelles, triggering the fluorescence response of multiple rather than a single FRET pair. In comparison to conventional FRET substrates where a single donor interacts with a single acceptor, the micellar multiplex FRET system showed ∼20- and ∼3-fold enhancements in the limit of detection and FRET efficiency, respectively. This supramolecular signal amplification approach could potentially be used to improve FRET-based diagnostic assays of nucleic acid and non-DNA based targets.

Self-assembled micellar nanostructures of ursolic acid-polyethylene glycol (UA-PEG) conjugate as efficient drug transporter system

Polymeric micelle-based drug delivery systems have been extensively studied by researchers due to their nanoscopic size and low toxicity. In this study, we have designed and synthesized an amphiphilic ursolic acid-polyethylene glycol conjugate, which on self-assembly results in micellar nanostructures. We conjugated ursolic acid (UA) with polyethylene glycol monomethyl ether in a single step in the presence of a condensing reagent, DCC/DMAP, and their self-assembly was monitored by DLS and TEM. Further an anticancer drug, doxorubicin (DOX), was encapsulated into the hydrophobic core of the self-assembled nanostructures. Due to strong interactions between DOX and UA, high encapsulation efficiency (85.3%) was obtained. The release pattern of DOX from the loaded nanostructures showed a sustained release of drug over a period of time. The projected system showed responsiveness towards lipase and hence, biodegradability aspect of the nanostructure (UA-PEG) was also investigated by lipase-mediated degradation studies. MTT experiments were also carried out on both normal HEK293 cells and MG-63 cancer cells and showed the non-toxic nature of the projected conjugate. These results ensure the promising potential of the projected system as an efficient drug delivery vehicle specifically to cancers cells in vivo and in vitro.

N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan: Synthesis, physicochemical and biological properties

Two samples of N-(2-hydroxy)-propyl-3-trimethylammonium, O-palmitoyl chitosan (DPCat) with different average degrees of quaternization named as DPCat35 (DQ¯ = 35%) and DPCat80 (DQ¯ = 80%), were successfully synthesized by reacting glycidyltrimethylammonium chloride (GTMAC) with O-palmitoyl chitosan (DPCh) derivative (DS¯ = 12%). Such amphiphilic derivatives of chitosan were fully water-soluble at 1.0 < pH < 12.0 and showed significant electrostatic stability enhancement of a self-assembly micellar nanostructure (100–320 nm) due to its positively-charged out-layer. In vitro mucoadhesive and cytotoxicity essays toward healthy fibroblast cells (Balb/C 3T3 clone A31 cell), human prostate cancer (DU145) and liver cancer (HepG2/C3A) cell lines revealed that the biological properties of DPCat derivatives were strongly dependent on DQ¯. Additionally, DPCat35 had better interactions with the biological tissue and with mucin glycoproteins at pH 7.4 as well as exhibited potential to be used on the development of drug delivery systems for prostate and liver cancer treatment.

Ultrasonic-Assisted Preparation of α-Tocopherol/Casein Nanoparticles and Application in Grape Seed Oil Emulsion

In this work casein (CN) was used as a carrier system for hydrophobic agent α-tocopherol (α-TOC), an amphiphilic self-assembling micellar nanostructure was formed with ultrasound-assistance. The interaction mechanism was detected by UV-Vis spectroscopy, Fluorescence spectroscopy and Fourier transform infrared spectroscopy (FTIR), the stability of the nanoparticles was investigated by the typical processing and storage conditions. Oil-in-water emulsion containing self-assembled nanoparticles was prepared with grape seed oil, the effect of emulsion oxidation stability was studied with the professional rancimat. Results showed that UV-Vis spectra of α-TOC/CN nanoparticles complexes were significantly different during ultrasonic treatments, which indicate an increase in its interation. Interaction between α-TOC and casein at different molar concentrations resulted in a quenching of the intrinsic fluorescence at 280 nm and 295 nm. Moreover, by using FTIR deconvolution analysis and multicomponent peak modeling, the relatively quantitative amounts of α-helical and β-sheet in protein secondary structure were obtained, the self-assembly nanoparticles can improve stability of α-TOC by protecting from degradation caused by light and oxygen. Importantly, both the concentrations of α-TOC/CN nanoparticles were able to inhibit lipid emulsion oxidation.

What happens when pesticides are solubilised in binary ionic/zwitterionic-nonionic mixed micelles?

HypothesisSurfactants have been widely used as adjuvants in agri-sprays to enhance the solubility of pesticides in foliar spray deposits and their mobility through leaf cuticles. Previously, we have characterised pesticide solubilisation in nonionic surfactant micelles, but what happens when pesticides become solubilised in anionic, cationic and zwitterionic and their mixtures with nonionic surfactants remain poorly characterised. ExperimentsTo facilitate characterisations by SANS and NMR, we used nonionic surfactant hexaethylene glycol monododecyl ether (C12E6), anionic sodium dodecylsulphate (SDS), cationic dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecylphosphocholine (C12PC) as model adjuvant systems to solubilise 3 pesticides, Cyprodinil (CP), Azoxystrobin (AZ) and Difenoconazole (DF), representing different structural features. The investigation focused on the influence of solubilisates in driving changes to the micellar nanostructures in the absence or presence of electrolytes. NMR and NOESY were applied to investigate the solubility and location of each pesticide in the micelles. SANS was used to reveal subtle changes to the micellar structures due to pesticide solubilisation with and without electrolytes. FindingsUnlike nonionic surfactants, the ionic and zwitterionic surfactant micellar structures remain unchanged upon pesticide solubilisation. Electrolytes slightly elongate the ionic surfactant micelles but have no effect on nonionic and zwitterionic surfactants. Pesticide solubilisation could alter the structures of the binary mixtures of ionic/zwitterionic and ionic/nonionic micelles by causing elongation, shell shrinkage and dehydration, with the exact alteration being determined by the molar ratio in the mixture.

Photocatalytically active block copolymer hybrid micelles from double hydrophilic block copolymers

Herein, we demonstrate that double hydrophilic block copolymers can be used for the preparation of photocatalytically active organic/inorganic hybrid micelles. This is realized by immobilization of CdS nanoparticles for photocatalytic water splitting within well-defined poly(2-iso-propyl-2-oxazoline)-block-poly(2-acrylamido glycolic acid) (PiPrOx-b-PAGA) block copolymers. The prepared PiPrOx-b-PAGA/CdS hybrid nanostructures were characterized regarding morphology, structure, and optical properties by UV/Vis and photoluminescence (PL) spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Our results confirm spherical inorganic-organic micelles containing ultra-small CdS nanoparticles with photoluminescent character within the core. Afterwards, these hybrid nanostructures were used for photocatalytic H2 production in the presence of triethanol amine (TEOA) as sacrificial reagent in water under visible-light illumination (λ ≥ 470 nm), revealing 18-fold increased activity compared to bare CdS nanoparticles. The enhanced photocatalytic activity can be attributed to several factors, such as 3D confinement within micellar nanostructures, the presence of ultra-small CdS nanoparticles, or an improved stability of CdS nanoparticles within the micellar core. Overall, we demonstrate that double hydrophilic BCP can be an interesting platform for the formation of photocatalytically active micellar nanostructures, leading to materials with potential relevance for photocatalysis.

A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors

Gadolinium-based contrast agents (GBCAs) are the most widely used T1 contrast agents for magnetic resonance imaging (MRI) and have achieved remarkable success in clinical cancer diagnosis. However, GBCAs could cause severe nephrogenic systemic fibrosis to patients with renal insufficiency. Nevertheless, GBCAs are quickly excreted from the kidneys, which shortens their imaging window and prevents long-term monitoring of the disease per injection. Herein, a nephrotoxicity-free T1 MRI contrast agent is developed by coordinating ferric iron into a telodendritic, micellar nanostructure. This new nano-enabled, iron-based contrast agent (nIBCA) not only can reduce the renal accumulation and relieve the kidney burden, but also exhibit a significantly higher tumor to noise ratio (TNR) for cancer diagnosis. In comparison with Magnevist (a clinical-used GBCA), Magnevist induces obvious nephrotoxicity while nIBCA does not, indicating that such a novel contrast agent may be applicable to renally compromised patients requiring a contrast-enhanced MRI. The nIBCA could precisely image subcutaneous brain tumors in a mouse model and the effective imaging window lasted for at least 24 h. The nIBCA also precisely highlights the intracranial brain tumor with high TNR. The nIBCA presents a potential alternative to GBCAs as it has superior biocompatibility, high TNR and effective imaging window.

Block Copolymer Micelles Generated by Crystallization-Driven Self-Assembly in Polymer Matrices

In this review, we show how Crystallization-Driven Self-Assembly (CDSA), a method originally employed for the self-assembly of block copolymers in solution, was extended to the synthesis of elongated micellar nanostructures in polymer matrices. By highlighting some of the works published by our group in this area, the conditions to synthesize nanostructured polymers by CDSA are discussed. The knowledge of these conditions will allow developing a new generation of nanomaterials with tailored architecture based on a given application.

In Vitro Assessment of Core-Shell Micellar Nanostructures of Amphiphilic Cationic Polymer-Peptide Conjugates as Efficient Gene and Drug Carriers

Design and development of biocompatible, biodegradable and stable dual delivery systems for drug and gene is the need of the hour. Here, we have designed a strategy to develop carrier systems consisting of above mentioned properties by (a) incorporating an unnatural amino acid in the peptide backbone, and b) conjugating a low molecular weight cationic polymer (polyethylenimine, PEI) for incorporating cationic charge. Using this strategy, we have synthesized a small series of Boc-FΔF-AH-polyethylenimine conjugates by varying the concentration of Boc-FΔF-aminohexanoic acid, viz., PP-1, PP-2 and PP-3. These conjugates self-assembled in aqueous medium to form micelles in the size range of ~144–205 nm with zeta potential ~ +7.9–14.2 mV bearing core-shell type of conformation. Positive surface of the micelles facilitated the binding of plasmid DNA as well as transportation inside the cells. The hydrophobic core of the nanostructures helped in the encapsulation of the hydrophobic drug molecule, which was then got released in a controlled manner. DNA complexes of the conjugates were not only found non-toxic but also exhibited higher transfection efficacy than the native polymer and Lipofectamine. Altogether, these nanostructures are capable of delivering a drug and a gene simultaneously in vitro and could be used as next-generation delivery agents.

Chain-End Modifications and Sequence Arrangements of Antimicrobial Peptoids for Mediating Activity and Nano-Assembly.

Poly(N-substituted glycine) “peptoids” are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid “tails” to generate “lipopeptoids” that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed—one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be “inert” even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 μM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids.

Effects of genipin concentration on cross-linked β-casein micelles as nanocarrier of naringenin: Colloidal properties, structural characterization and controlled release

β-casein (β-CN), an amphiphilic protein from bovine milk, has attracted increasingly interest as biocompatible, non-toxic nanocarrier in foods due to its ability to form micellar nanostructures through self-assembling. In this study, the formation of genipin-crosslinked β-casein micelles (G-CNMs) was investigated for the delivery of naringenin, a hydrophobic flavonoid abundant in grapefruits. Our results showed that the degree of micellar crosslinking was dependent on the genipin concentration, as indicated by SDS-PAGE and GPC-MALLS. At the suitable genipin concentration (β-CN/genipin molar ratio of 1:20), the G-CNMs showed intra-micellar crosslinking with average hydrodynamic radius (9.35 nm) as measured by dynamic light scattering. We found that the degree of crosslinking has a significant influence on the aspects of stability and controlled release. G-CNMs overcame destabilization of micelles induced by acid pH (pH = 2) when β-CN/genipin molar ratio was 1:15 or 1:20, while the stability against the high NaCl concentration was not influenced. Specifically, as compared to untreated CNMs, all types of G-CNMs in phosphate buffered saline buffer (10 mM, pH 7.4) revealed slower releases of naringenin. With the increase of genipin amount, the controlled drug release properties was enhanced. Such findings appear to be promising for future applications of β-CN as controlled release nanocarrier for hydrophobic functional ingredient, whose characteristics can be modulated by tailored genipin crosslinking.

Polymeric micelles containing resveratrol: development, characterization, cytotoxicity on tumor cells and antimicrobial activity

Antimicrobial and antitumor activities of resveratrol, a compound found mainly in grapes, have already been demonstrated. However, its low bioavailability is a limiting factor for therapeutic application. Polymeric micelles can be an approach to solve this problem since they can encapsulate hydrophobic substances. We developed and characterized micellar formulations containing resveratrol and evaluated their cytotoxic and antimicrobial effects. The formulations were prepared by the cold dispersion method with different concentrations of F127 (5 or 10% w/w) and resveratrol (500 or 5000 µM). The formulations were characterized according to size, polydispersity index, pH, encapsulation rate and in vitro release. Cytotoxic effect was evaluated on a bladder cancer cell line and antimicrobial effect was evaluated on E. coli, S. aureus and C. albicans. One of the formulations (10% w/w of F127 and 5000 µM of resveratrol) was a monodispersed solution with high encapsulation rate, thus it was chosen for the cytotoxicity and antimicrobial assays. MS- 10+RES-3 was able to preserve the antimicrobial and cytotoxic activity of resveratrol. This is the first study that evaluated antimicrobial potential and cytotoxicity of micelles containing resveratrol on bladder cancer cells and the results showed that micellar nanostructures could ensure the maintenance of the biological activity of resveratrol.

Transition metal decorated soft nanomaterials through modular self-assembly of an asymmetric hybrid polyoxometalate.

An asymmetrically functionalised Wells-Dawson organic-inorganic hybrid polyoxometalate has been post-functionalised by Pt2+ coordination, and demonstrates self-assembly into surface-decorated micellar nanostructures. This multifunctional hybrid material is found to be a redox-active soft nanomaterial and demonstrates a new molecular design strategy with potential for applications in photo- or electro-catalysis.

Artesunate-heparin conjugate based nanocapsules with improved pharmacokinetics to combat malaria

Artesunate-heparin conjugate (ART-HEP) based nanocapsules as drug delivery vehicle was developed for intracellular release of ART in malaria therapy. Owing both hydrophobic and hydrophilic moieties, the conjugate was successfully self-assembled into artesunate-heparin nanocapsules (ART-HEP-NCPs) with lower critical micelle concentration (CMC) of about 20 µg/mL. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed that ART-HEP-NCPs has an average hydrodynamic diameter of 112.1 nm with a negatively charged surface (−11.2 mV) and typical micellar nanostructure, respectively. Interestingly, such modification achieved high drug loading efficiency (DLE) of ART (29.3 wt%), which is significantly higher than already reported conventional ART-loaded nanoparticles. The nanocapsules demonstrated lower in vitro ART release under neutral physiological environment (33.81%) but higher release rate was observed in simulated acidic microenvironment (92.74%) in 70 h test. This behavior of ART-HEP-NCPs will facilitate the intracellular release of ART under slightly acidic parasitic food vacuole for effective antimalarial effect. Storage stability and hemolytic studies exhibited that ART-HEP based nanocapsules were stable and safe for intravenous (i.v) injection. Notably, ART-HEP-NCPs has promising internalization into Plasmodium infected red blood cells (iRBCs) and also displayed in vitro inhibitory effect against P. falciparum 3D7 with half-maximal inhibitory concentration (IC50) of 10.16 nM, which was slightly higher than free ART (IC50 6.27 nM). This expected slightly lower inhibitory effect of polymeric prodrug could be ascribed to the gradual release of ART from the polymer chain over time. More importantly, the in vivo pharmacokinetics study indicated that the nanoscale characteristic of nanocapsules substantially contributed to the extended circulation of ART in blood. In conclusion, such multifunctional ART-HEP-NCPs with higher ART loading and extended half-life could be a promising platform for targeted antimalarial drug delivery.

What happens when pesticides are solubilized in nonionic surfactant micelles

Nonionic surfactants have been widely used in agri-sprays to enhance the solubility and mobility of pesticides, but what happens when pesticides become solubilized into surfactant micelles remains poorly characterized. To facilitate physical characterisations, we used the nonionic surfactant hexaethylene glycol monododecyl ether (C12E6) as a model system to solubilize 4 pesticides including Cyprodinil (CP), Diuron (DN), Azoxystrobin (AZ) and Difenoconazole (DF). The investigation focused on the influence of solubilizate and temperature in driving changes to the micellar nanostructures. Dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo-TEM) and small-angle neutron scattering (SANS) measurements were used to reveal changes to the micellar structure before and after pesticide solubilisation. Nuclear magnetic resonance (NMR) was also applied to investigate the solubility and location of each pesticide in the micelles. Pesticides clearly altered the micellar structure, by increasing the aggregation number and micellar lengths, whilst shrinking and dehydrating the shells, leading to a consequent decrease in the dispersion cloud points. Increases in temperature affected micellar structures in a similar way. Thus, temperature increases and the solubilisation of pesticides can both make the surfactant effectively more hydrophobic, altering the micellar nanostructures and shifting the pesticide location within the micelles. These changes subsequently implicate how pesticides are delivered into plants through the natural wax films.

Amphiphilic Bottlebrush Block Copolymers: Analysis of Aqueous Self-Assembly by Small-Angle Neutron Scattering and Surface Tension Measurements

A systematic series of 16 amphiphilic bottlebrush block copolymers (BCPs) containing polystyrene and poly(N-acryloylmorpholine) (PACMO) side chains were prepared by a combination of atom-transfer radical polymerization (ATRP), photoiniferter polymerization, and ring-opening metathesis polymerization (ROMP). The grafting-through method used to prepare the polymers enabled a high degree of control over backbone and side-chain molar masses for each block. Surface tension measurements on the self-assembled amphiphilic bottlebrush BCPs in water revealed an ultralow critical micelle concentration (cmc), 1–2 orders of magnitude lower than linear BCP analogues on a molar basis, even for micelles with >90% PACMO content. Combined with coarse-grained molecular dynamics simulations, fitting of small-angle neutron scattering traces (SANS) allowed us to evaluate solution conformations for individual bottlebrush BCPs and micellar nanostructures for self-assembled macromolecules. Bottlebrush BCPs showed an increase in a...

Nanoencapsulation of quercetin and curcumin in casein-based delivery systems

Direct incorporation of hydrophobic nutraceuticals into liquid foods faces different technological challenges, namely low water-solubility and limited physiochemical stability. Nanoencapsulation may facilitate dissolution and protection of lipophilic bioactives. In this study, a hierarchical approach (ligand binding to sodium caseinate and then either re-assembling the micellar nanostructures or formation casein nanoparticles) was used to encapsulate two phenolic compounds, including curcumin and quercetin. As determined by spectrofluorometry, the binding stoichiometry of quercetin and curcumin were 0.96 and 0.78, respectively. The average particle size of re-assembled casein micelles (r-CMs) was smaller than that of casein nanoparticles (CNPs). The effect of quercetin loading on increasing the particle size of r-CMs was higher than that of curcumin loading due to the higher binding affinity of quercetin. The entrapment efficiency of both ligands was higher than 90%. The ejection of ligands from the nanocarriers was negligible over time, but not as a function of pH in the case of quercetin-loaded nanocarriers. Both CNP and r-CM significantly improved the chemical stability of phenolic compounds during an accelerated shelf-life test. Formation of r-CMs was confirmed, likely for the first time, by measuring the changes in the relative viscosity during the re-assembly process. The aqueous solubility of curcumin and quercetin after loading in r-CMs was higher than that of free polyphenol molecules. Generally, the viability of MCF-7 human breast cancer cells in the presence of different samples followed this order: digested polyphenol-loaded r-CMs < non-digested polyphenol-loaded carriers < free polyphenol molecules. TEM images confirmed the formation of r-CMs.

Drug Delivery Systems from Self-Assembly of Dendron-Polymer Conjugates †.

This review highlights the utilization of dendron-polymer conjugates as building blocks for the fabrication of nanosized drug delivery vehicles. The examples given provide an overview of the evolution of these delivery platforms, from simple micellar containers to smart stimuli- responsive drug delivery systems through their design at the macromolecular level. Variations in chemical composition and connectivity of the dendritic and polymeric segments provide a variety of self-assembled micellar nanostructures that embody desirable attributes of viable drug delivery systems.