Micelle-like Structures Research Articles

Conformation and Aggregation of Selectively PEGylated and Lipidated Gastric Peptide Hormone Human PYY3-36.

The gastric peptide hormone human PYY3-36 is a target for the development of therapeutics, especially for treatment of obesity. The conformation and aggregation behavior of PEGylated and lipidated derivatives of this peptide are examined using a combination of fluorescence dye assays, circular dichroism (CD) spectroscopy, analytical ultracentrifugation (AUC) measurements, small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM). The behavior of two PYY3-36 derivatives lipidated (with octyl chains) in different positions is compared to that of two derivatives with PEG attached at different residues and to that of the native peptide. We find that, unexpectedly, PYY3-36 forms amyloid fibril structures above a critical aggregation concentration. Formation of these structures is suppressed by PEGylation or lipidation. PEGylation significantly reduces the (reversible) loss of α-helix content observed on heating PYY3-36. The PEG conjugates form mainly monomeric structures in solution- coiled-coil formation, and other aggregation presumably being sterically hindered by swollen PEG chains. However, some small aggregates are detected by AUC. In complete contrast, both of the two lipidated peptides show the formation of spherical micelle-like structures which are small oligomeric aggregates. Our findings show that PEGylation and lipidation are complementary strategies to tune the conformation and aggregation of the important gastric peptide hormone human PYY3-36.

Excited-state prototropism of 7-hydroxy-4-methylcoumarin in [Cnmim][BF4] series of ionic liquid-water mixtures: insights on reverse micelle-like water nanocluster formation.

This study explores the excited state prototropic behavior of the fluorophore, 7-hydroxy-4-methylcoumarin (7H4MC), in the [Cnmim][BF4] (n = 2, 4, 6, 8, 10) series of ionic liquid (IL)-water mixtures at low water contents. In pure IL media, 7H4MC exists in the neutral form in both ground and excited states. However, on addition of water to the ILs, the excited neutral form of the dye is gradually converted to the anionic and the tautomeric species, leading to characteristic changes in the emission spectra. The similarity in the spectral features of 7H4MC in the IL-water system with that in a conventional reverse micelle system rather than with organic solvent-water mixtures, suggests that in the presence of water, the ILs are organized into reverse micelle-like structures with the consequent formation of confined water pockets. The results further suggest that formation of water nanoclusters and the ensuing changes in excited state prototropic behavior of the dye, is facilitated by increase in the alkyl chain length of the IL cation. These propositions are supported by time-resolved fluorescence studies. To the best of our knowledge this is the first report on proton transfer reaction in IL-water mixtures at low water contents. Considering that ILs are useful as solvents and surfactants, and IL-water mixtures in particular have applications in chemical extractions and biocatalysis, an understanding of the structural organization and water pool formation in these systems is quite important. The insights obtained from the prototropic transformations of 7H4MC are significant not only for fundamental self-assembly studies, but also for the development of ILs as chemical reaction media.

Molecular interactions between Pluronic F127 and the peptide tritrpticin in aqueous solution

Triblock copolymers, such as Pluronic F127 (F127), are pharmaceutically important amphiphilic compounds that self-assemble in aqueous solution either as discrete or entangled micelles, depending on their concentration and temperature, which may function as drug delivery vehicle. Herein, we have synthesized the antimicrobial peptide tritrpticin (TRP3), a tryptophan (Trp)- and arginine (Arg)-rich peptide, sequence VRRFPWWWPFLRR, with a broad spectrum of action against bacteria and fungi, to investigate its interaction with F127 in dilute aqueous solution, by using fluorescence and circular dichroism spectroscopies, differential scanning calorimetry, dynamic light scattering, and zeta potential methods. The combined results indicate that at 50 μmol L−1 TRP3 and up to 700 μmol L−1 F127, these compounds interact together to form F127-bound complexes with the peptide at low concentrations, and immobilized TPR3-containing micelle-like structures at higher concentrations. The F127-TRP3 complexes are stable with varying hydrodynamic size depending on the relative amount of F127, which can be tuned smaller by adjusting the copolymer concentration to values suitable for drug delivery applications in biomedicine.

Phase behavior and alignment transition of ultra high molecular weight polyethylene/polyamide 6 blends under extensional and shear flow

Herein, we have, for the first time, presented detailed comparative studies on complex phase behavior and alignment transition of ultra high molecular weight polyethylene/polyamide 6 (UHMWPE/PA6) blends under unconventional extensional flow and traditional shear flow by combined atomistic and mesoscopic simulation. The Flory-huggins interaction parameter χ, a bridge between atomistic and mesoscopic simulation, was calculated based on atomistic simulation, taking into account the chemical constitution of UHMWPE/PA6 blends. It is found that these blends with differential mass fraction are preferentially aligned into parallel or perpendicular orientations with zero flow. When subjected to extensional (pressure-driven) flow, the aligned aggregates reorient and these elongated aggregates are divided into discrete micelles, leading to the appearance of a thinner layer and a more homogeneous phase at a high pressure. In sharp contrast, when the mesoscopic behaviors were imposed by a shear flow over a series of shear rates, the blend systems preferentially form micelle-like structures at low shear rate, similar to the case under pressure-driven force, and transform to transverse lamella alignment with further increasing shear rate to γ̇ = 0.1, which indicates that the shear flow not only induces the orientation of alignments, but also regulates the ordered distribution of aggregates.

Non-Covalently Functionalized Boron Nitride Mediated by a Highly Self-Assembled Supramolecular Polymer

A new method for exfoliation of hexagonal boron nitride (h-BN) into few-layered nanosheets has been developed by employing noncovalent assembly of networks upon association with a supramolecular polymer. In this work, we developed a simple, reliable, effective approach for preparation of exfoliated h-BN nanosheets from bulk h-BN via liquid-phase exfoliation using a low-molecular weight adenine-functionalized polypropylene glycol (A-PPG) supramolecular polymer. A-PPG self-assembled into either long-range ordered lamellar or micelle-like structures on the surface of h-BN because of the strong specific interactions between A-PPG and h-BN. The level of h-BN nanosheet exfoliation could be controlled by adjusting the amount of A-PPG incorporated. This newly developed composite exhibited excellent phase transition behavior and thermal stability, and few-layer thickness with good dispersion of h-BN nanosheets, indicating self-assembled A-PPG functions as an efficient dispersant and stabilizer to manipulate the ph...

Smart Amphiphilic Janus Microparticles: One-Step Synthesis and Self-Assembly.

Self-assembly is the process to form ordered compound structures. Theories and experiments involving nanosized Janus particles have proved that the assembled cluster structures are related to the unit number. Micrometer-sized amphiphilic Janus particles could also act as surfactants to stabilize droplets and aggregate to form clusters. When the scale order increases to the millimeter size, particles are usually connected under shape-match mechanism, which means that the assembled structure is related to the particular particle morphology rather than the particle number. Similar to millimeter-sized particles, sub-millimeter-sized particles are larger and heavier such that their gravity cannot be ignored, whereas their Brownian motion could be neglected. To investigate the self-assembly behavior of sub-millimeter-sized Janus particles, we synthesize smart amphiphilic Janus microparticles directly from water-oil Janus droplets in one step by using a double-core capillary device. We find that the amphiphilic Janus particles could also be distributed directionally between the sides of the water-oil interface. When in oil solutions with several water droplets, the particles self-assemble into micelle-like structures to cover the water droplets with the hydrophilic phase inside. After evaporation, structures with a hydrophilic concave and a hydrophobic convex are formed. This paper demonstrates that sub-millimeter-sized amphiphilic Janus particles exhibit similar ability to nano-sized Janus particles to aggregate into clusters with ordered structures.

The mechanism for the complexation and dissociation between siRNA and PMAL: a molecular dynamics simulation study based on a coarse-grained model

The capacity of silencing genes makes small interfering RNA (siRNA) becomes potential candidates for curing many fatal diseases. Due to the low stability and delivery efficiency of siRNA, the design of amphiphilic carrier for siRNA delivery is vital for the practical gene therapy. In the present work, we explored how the complexation and dissociation of siRNA with poly (maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine (PMAL), which is a recent synthesised amphiphilic polymer and can be used in delivery of siRNAs and proteins, using traditional molecular dynamics simulations, together with steered molecular dynamics simulations. It was shown that the complexation of siRNA with PMALs can spontaneously occur, no matter what unit number of PMAL is. PMALs of different unit numbers form micelle-like structures and interact with siRNA surface. With the increase of unit number, PMAL becomes more flexible and interacts with siRNA from attachment to entanglement. The dissociation of PMAL from siRNA is an energy-consuming process. The free energy difference increases with the unit number of PMAL. The free energy for dissociation involves both the stretch of PMAL and the separation of PMAL from siRNA. Therefore, an optimal unit number of PMAL is critical for the delivery efficiency of siRNA when PMAL is used as carrier. In present work, when the radius of gyration of PMAL approaches to that of siRNA, PMAL gives a favoured both complexation and dissociation between siRNA and PMAL. Finally, we propose the mechanism of complexation and dissociation of PMAL with siRNA. The above simulation established a molecular insight of the interaction between siRNA and PMAL and was helpful for the design and applications of new PMAL-based polymers as siRNA delivery carriers.

Micelles of the chiral biocompatible surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB): molecular dynamics and fragmentation patterns in the gas phase.

The study of self-assembly processes of surfactant molecules in the gas phase is of great interest for several theoretical and technological reasons related to their possible exploitation as drug carriers, protein shields and cleaning agents in the gas phase. The stability and fragmentation patterns of singly and multiply charged (either positively or negatively) aggregates of the surfactant (1R,2S)-dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethyl ammonium bromide (DMEB) in the gas phase have been studied by ion mobility mass spectrometry and tandem mass spectrometry. Molecular dynamics (MD) simulations of positively and negatively singly and multiply charged DMEB aggregates have been performed to obtain structural and energetics information. Finally, in order to ascertain some clues on the DMEB growth mechanism, quantum mechanics calculations were carried out. It has been evidenced that positively and negatively singly charged aggregates at low collision energy decompose preferentially by loss of only one DMEB molecule. Increasing the collision energy, the loss of neutrals becomes increasingly abundant. Multiply charged DMEB aggregates are unstable and decompose forming singly charged monomers or dimers. MD simulations show reverse micelle-like structures with polar heads somewhat segregated into the aggregate interior. Finally, a good correlation between experimental and calculated collisional cross sections (CCS) was found. The fragmentation pathways of DMEB charged species evidenced for singly charged aggregates exhibit features similar to that of other detergent aggregates, but multiply charged aggregates showed a system-specific behavior. QM calculations on the optimized structures (21+ , 31+ , 11- and 21- ) indicate that the most determinant interactions are due to an OH---Br hydrogen bonding that is also involved in the link between monomeric DMEB units. The MD models gave CCS values in good agreement with experimental ones, evidenced by a less strict reverse micelle-like structure and a reasonably spread bromine anion distribution Copyright © 2017 John Wiley & Sons, Ltd.

A novel hybrid solid dispersion film coat as a moisture barrier for pharmaceutical applications

In the present study, a novel hybrid moisture barrier film coat, based on a solid dispersion of stearic acid (SA) in hydroxypropyl cellulose (HPC) using a polymeric surface active agent (PSAA), has been developed. The hybrid free films, prepared by a solution casting method, were characterized by water vapor transmission rate, DSC, mechanical tests, SEM and contact angle measurement to assess the structure-properties relationships of the films. The hybrid film formulations were then used to coat tablets containing CaCl2 as a moisture absorbing agent to study the coating and sealing properties of the films. The results have shown that a specific weight ratio between the components could considerably increase the barrier capability of the film against moisture as compared to either pure HPC or the combination of HPC and SA, while keeping the basic properties of the HPC. This specific feature could be attributed to the presence of PSAA in the film, which may form micelle-like structures entrapping the SA, resulting in a reduced interfacial tension and thus a tight integration between two opposing phases (HPC and SA). By this means the micro-sized SA particulates could be evenly dispersed within the HPC matrix to obtain an efficient solid dispersion.

Polyoxometalate-Engineered Building Blocks with Gold Cores for the Self-Assembly of Responsive Water-Soluble Nanostructures.

The controlled assembly of gold nanoparticles (AuNPs) with the size of quantum dots into predictable structures is extremely challenging as it requires the quantitatively and topologically precise placement of anisotropic domains on their small, approximately spherical surfaces. We herein address this problem by using polyoxometalate leaving groups to transform 2 nm diameter gold cores into reactive building blocks with hydrophilic and hydrophobic surface domains whose relative sizes can be precisely tuned to give dimers, clusters, and larger micelle-like organizations. Using cryo-TEM imaging and 1 H DOSY NMR spectroscopy, we then provide an unprecedented "solution-state" picture of how the micelle-like structures respond to hydrophobic guests by encapsulating them within 250 nm diameter vesicles whose walls are comprised of amphiphilic AuNP membranes. These findings provide a versatile new option for transforming very small AuNPs into precisely tailored building blocks for the rational design of functional water-soluble assemblies.

Visible light-switched cytosol release of siRNA by amphiphilic fullerene derivative to enhance RNAi efficacy in vitro and in vivo.

We designed a novel photosensitive amphiphilic carrier (C60-Dex-NH2) for efficient and controllable siRNA delivery, which can be used in gene therapy. We showed that C60-Dex-NH2 could destroy lysosome membrane via controllable generation of ROS when exposed to light, which can help siRNA to escape from lysosome before degradation. This can enhance the gene silencing efficiency significantly and provides a useful way to regulate RNAi efficiency by light. One advantage for C60-Dex-NH2 system is C60 has broad absorbance spectrum and can be activated by weak visible light; Furthermore, C60-Dex-NH2 has a specific amphiphilic structure, which may prevent siRNA from degrading and allows C60-Dex-NH2 to embed into the lipid membrane of lysosome to improve the ROS induced lysosomal disturbance after internalization.

The relationship between micelle formation and biological activity of peptide 562–572 of luteinizing hormone receptor modified with decanoyl radicals

Lipophilic derivatives of peptides corresponding to cytoplasmic regions of G protein-coupled receptors (GPCR) can act as intracellular agonists. Our previous work showed that peptides corresponding to residues 562–572 of luteinizing hormone receptor and modified with palmitate or decanoate at the C-terminus activate adenylate cyclase in rat testes. The stimulating effect of peptide 562–572 modified with decanoates at both the N- and the C-termini (peptide IV) reached its maximum at the peptide concentration of 10–5 M and diminished with further increase in its concentration. It was supposed that this effect was due to peptide IV ability to form micelles. To verify this hypothesis, the relationship between biological activity, hydrophobicity, and ability to form micelles was investigated for peptide IV and other acylated derivatives of peptide 562–572, including those carrying C-terminal decanoate (peptide III) and palmitate (peptide VI) moieties. It was found that the stimulating effect of peptide IV taken in the concentration of 10–5 M on adenylate cyclase activity in plasma membranes of rat testes and ovaries was only slightly lower than that of peptide VI and higher than the effect of peptide III. At the concentration of 10–3 M, the effect of peptide IV was 20–27% lower and amounted to only 50–51 and 87–88% of the effects of peptides VI and III, respectively. In spite of its high hydrophobicity, peptide IV was characterized with an abnormally low retention time when eluted from a Nucleosil C8 column during reverse-phase HPLC: it was even lower than the retention time of nonmodified peptide 562–572. However, the retention time of peptide IV, but not of other peptides, increased significantly when the eluent contained a higher proportion of trifluoroacetic acid, which disrupts micellelike structures (0.5 instead of 0.1%). The surface tension of peptide IV solution in water slightly decreased with increasing peptide concentration, but rapidly dropped and reached a plateau at the concentration of 7 × 10–6 M, which indicates the beginning of micelle formation. Thus, peptide IV in the concentrations above 10–5 M forms micelles, which prevents it from interacting with the receptor. The ability of GPCR peptides to aggregate and form micelles should be taken into account in the development of their new membrane-active analogs.

Structures of single, double and triple layers of lipids adsorbed on graphene: Insights from all-atom molecular dynamics simulations

Non-covalent functionalization of graphene with phospholipids is a promising technique for biosensing applications and intracellular delivery of analytical probes and drugs. However, molecular details of the self-assembly of lipids on graphene surface is still poorly understood and hard to control. There is a clear lack of understanding of why various kinds of lipid aggregates can form on graphene. In the current work, we address this question by investigating equilibrium and dynamical properties of lipid layers adsorbed on graphene in water environment and in vacuum using all-atom Molecular Dynamics simulations. It is shown that a variety of lipid aggregates can form on top of graphene depending on initial orientation, number of adsorbed lipid layers and the presence of water. The lipid layers self-organize and reorient in order to minimize hydrophobic mismatch on graphene-lipid, lipid-lipid and water-lipid interfaces. Obtained structures range from homogeneous layers to the networks of inverted micelle-like structures and weakly bound cylindrical micelles on top of monolayers. Our results are in excellent agreement with recent experimental findings. Another pronounced effect of graphene is the strong ordering of the lipid atoms which are in direct contact with it. In all studied systems at least two well-structured atomic shells are formed above the graphene surface at the distances of 0.35 and 0.85 nm.

Liquid Crystalline Granules Align in a Hierarchical Structure To Produce Spider Dragline Microfibrils.

The spider silk spinning process converts spidroins from an aqueous form to a tough fiber. This spinning process has been investigated by numerous researchers, and micelles or liquid crystals of spidroins have been reported to form silk fibers, which are bundles of silk microfibrils. However, the formation process of silk microfibrils has not been clarified previously. Here, we report that silk microfibrils are generated through the formation, homogenization, and linkage of liquid crystalline granules without micelle-like structures. Heterogeneous granules on the submicron to micron scale were observed in the storage sac, whereas homogeneous granules with diameters of approximately 100 nm were aligned along the tapering duct. In the spun fibers, the homogeneous granules were connected along the fiber axis. This is the first clear description of the formation of granule-based microfibrils in the spinning process, which is the key conversion process leading to the unique hierarchical structure of spider dragline.

Amphiphilic Polypeptoids Serve as the Connective Glue to Transform Liposomes into Multilamellar Structures with Closely Spaced Bilayers.

We report the ability of hydrophobically modified polypeptoids (HMPs), which are amphiphilic pseudopeptidic macromolecules, to connect across lipid bilayers and thus form layered structures on liposomes. The HMPs are obtained by attaching hydrophobic decyl groups at random points along the polypeptoid backbone. Although native polypeptoids (with no hydrophobes) have no effect on liposomal structure, the HMPs remodel the unilamellar liposomes into structures with comparable diameters but with multiple concentric bilayers. The transition from single-bilayer to multiple-bilayer structures is revealed by small-angle neutron scattering (SANS) and cryo-transmission electron microscopy (cryo-TEM). The spacing between bilayers is found to be relatively uniform at ∼6.7 nm. We suggest that the amphiphilic nature of the HMPs explains the formation of multibilayered liposomes; i.e., the HMPs insert their hydrophobic tails into adjacent bilayers and thereby serve as the connective glue between bilayers. At higher HMP concentrations, the liposomes are entirely disrupted into much smaller micellelike structures through extensive hydrophobe insertion. Interestingly, these small structures can reattach to fresh unilamellar liposomes and self-assemble to form new two-bilayer liposomes. The two-bilayer liposomes in our study are reminiscent of two-bilayer organelles such as the nucleus in eukaryotic cells. The observations have significance in designing new nanoscale drug delivery carriers with multiple drugs on separate lipid bilayers and extending liposome circulation times with entirely biocompatible materials.

Thermo-induced multistep assembly of double-hydrophilic block copolypeptoids in water

The aqueous solution behavior of thermoresponsive-hydrophilic block copolypeptoids, i.e., poly(N-(n-propyl)glycine) x -block-poly(N-methylglycine) y (x = 70; y = 23, 42, 76), in the temperature range of 20–45 °C is studied. Turbidimetric analyses of the 0.1 wt% aqueous solutions reveal two cloud points at T cp∼30 and 45 °C and a clearing point in between at T cl∼42 °C. Temperature-dependent dynamic light scattering (DLS) suggest that right above the first collapse temperature, single polymer molecules assemble into large structures which upon further heating, i.e., at the clearing point temperature, disassemble into micelle-like structures. Upon further heating, the aggregates start to grow again in size, as recognized by the second cloud point, through a crystallization process.

Amphiphilic carbon dots as versatile vectors for nucleic acid and drug delivery.

Carbon dot (CD)-based multifunctional delivery systems have shown great potential in both drug/gene delivery and bio-imaging. In this work, we present a strategy to simply construct amphiphilic CDs (ACDs) by conjugating hydrophobic alkyl epoxide to the surface amino groups of PEI 600-derived CDs. ACDs could well dissolve in water or organic solvents and emit bright fluorescence both in solutions and cells. 1HNMR also suggested that ACDs may form micelle-like structures in water, and their CMC could be determined. Enhanced green fluorescent protein (EGFP) expression and flow cytometry experiments showed that ACDs have higher transfection efficiency than Lipofectamine 2000 in A549 cells. Besides DNA, ACDs could also effectively transfect Sur siRNA toward A549 cells and cause early cell apoptosis. The 3D multicellular spheroids further confirmed their high potential for delivering therapeutic genes into the tumor tissue. On the other hand, ACDs also exhibited good drug loading ability. CLSM experiment results showed that DOX could be effectively internalized by the cell and slowly released from the drug/ACD complex. These results suggest that ACDs may not only serve as versatile delivery vectors with potential for applications in clinical cancer treatment, but also offer an inspiration for the discovery of CD-based gene/drug delivery systems.

Multicore Unimolecular Structure Formation in Single Dendritic–Linear Copolymers under Selective Solvent Conditions

The conformational and thermodynamic properties of single dendritic–linear copolymers are investigated by analytical models and computer simulations. Applying poor solvent conditions on the dendritic part, these molecules are known to form single unimolecular micelle-like structures. A mean-field model applying the Daoud–Cotton approach and a surface tension argument is presented and suggests the splitting of the unimolecular single-core structure into a multicore structure with increasing dendrimers generation and decreasing solvent selectivity. Monte Carlo simulations utilizing the bond fluctuation model with explicit solvent are performed which show the formation of multicore structures for trifunctional codendrimers of different generations and spacer lengths with linear chains attached to the terminal groups. These findings are aimed to understand the physics of spontaneous self-assembly of codendrimers in various well-defined macro-conformations under change of environmental conditions with potentia...

Multi-responsive fluorescence of amphiphilic diblock copolymer containing carboxylate azobenzene and N-isopropylacrylamide

Abstract One amphiphilic diblock copolymer poly(NIPAm-b-M6AzCOONa) with well-defined structure was synthesized by RAFT polymerization, in which N -isopropylacrylamide (NIPAM) was introduced as one thermoresponsive unit, and 6-[4-(4-sodium carboxylatephenylazo)phenoxyl]hexyl methacrylate (M6AzCOONa) was designed as pH-, UV-responsive and fluorescent units. The block copolymer was non-fluorescent in good solvent, but showed fluorescence emission when it formed micelle-like structures in water. The acquired fluorescence can be adjusted by UV or pH, which was strongly related to the aggregation tightness and size of the micelles. The block copolymer also showed reversible fluorescent enhancement in a large range of pH value (pH = 3–11) driven by thermally-induced coil-to-globule transition due to the existence of the PNIPAm block, which leads to a more closely-tightened aggregation of azobenzene moieties. These multiple-responsive fluorescence behaviors enable the amphiphilic block copolymer to find its applications for wide-pH-range fluorescence thermometer and fluorescence probe.

Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects.