Synthesis and Characterization of High Concentration Block Copolymer-Mediated Gold Nanoparticles

The formation of high concentration gold nanoparticles at room temperature is reported in block copolymer-mediated synthesis where the nanoparticles have been synthesized from hydrogen tetrachloroaureate(III) hydrate (HAuCl4·3H2O) using block copolymer P85 (EO26PO39EO26) in aqueous solution. The formation of gold nanoparticles in these systems has been characterized using UV−visible spectroscopy and small-angle neutron scattering (SANS). We show that the presence of additional reductant (trisodium citrate) can enhance nanoparticle concentration by manyfold, which does not work in the absence of either of these (additional reductant and block copolymer). The stability of gold nanoparticles with increasing concentration has also been examined

Unfolding and Refolding of Protein by a Combination of Ionic and Nonionic Surfactants

The interaction of protein and surfactant yields protein–surfactant complexes which have a wide range of applications in the cosmetics, foods, and pharmaceutical industries among others. Ionic and nonionic surfactants are known to interact differently with the protein. The interplay of electrostatic and hydrophobic interactions governs the resultant structure of protein–surfactant complexes. The present study enlightens the paramount role of the hydrophobic interaction, tuned by the hydrophobic tail length of ionic surfactants, in the unfolding of anionic bovine serum albumin (BSA) protein. The unfolding of BSA in the presence of four different tail-length cationic surfactants, that is, C10TAB, C12TAB, C14TAB, and C16TAB, has been investigated by small-angle neutron scattering and dynamic light scattering. All cationic surfactants unfold the protein at a certain concentration range. The propensity of protein unfolding increases with increasing the hydrophobic tail length. The denatured structure of BSA upon addition of cationic surfactants is characterized by the random flight model representing a beads-on-a-string chain-like complex. The unfolded protein binds the surfactant micelles in the protein–surfactant cluster. The micelles get elongated with the increasing concentration of cationic surfactants, whereas the number of micelles per cluster is decreased. In the final stage, the protein–surfactant cluster merges to one large micelle with unfolded protein wrapping the micelle surface. The pathway of protein unfolding is described in terms of the changes in the micellar size, the number of micelles formed per cluster, the separation between the micelles in the cluster, the aggregation number of micelles, and the number of proteins per cluster. The protein–surfactant interaction is further examined in the presence of a nonionic surfactant, that is, C12E10. The nonionic surfactant significantly suppresses the interaction of BSA protein with ionic surfactants by forming mixed micelles. As a result of the mixed micelles formation by ionic–nonionic surfactants, the ionic surfactant moves out from the unfolded BSA protein, and this enables the protein to refold back to its native structure. The propensity of mixed micelle-driven refolding of proteins is significantly changed with changing the tail length of the ionic surfactant

Exploring Physicochemical Interactions of Different Salts with Sodium <i>N</i>‑Dodecanoyl Sarcosinate in Aqueous Solution

Amino acid-based surfactants are used in academics and industry. Sodium N-dodecanoyl sarcosinate (SDDS) is such an amino acid-based surfactant having applications in pharmaceutical, food, and cosmetic formulations. Although the surface properties of this surfactant have been studied in the presence of univalent cationic and anionic salts, there is no report on such solution in the presence of higher valencies. In this experiment, critical micelle concentration (CMC) of SDDS from tensiometry, conductometry, and fluorimetry has been determined. In each case, CMC decreases with increasing salt concentration. Counterion binding of micelles (β), diffusion coefficient (D0), and surface properties, e.g., Gibbs free energy for micellization (ΔGm0), Gibbs surface excess (Γmax), area of exclusion per surfactant monomer (Amin), surface pressure at CMC (πcmc), etc., have been evaluated using methods such as tensiometry, conductometry, and fluorimetry. The hydrodynamic radius of SDDS in the presence of different salts was measured by the light scattering method. Aggregation number and shape of micelle have been determined by small-angle neutron scattering experiment. The nature of amphiphilic packing and the aggregation numbers of the assemblies have also been explored. The results from different experiments have been rationalized and represented systematically

Mixed Pluronic/lecithin micelles formulation for oral bioavailability of candesartan cilexetil drug: <i>in vitro</i> characterization and <i>in vivo</i> pharmacokinetic investigations

This study aimed to develop a mixed polymeric micelle formulation incorporating candesartan cilexetil (CAND) drug to enhance its oral bioavailability for the better treatment of hypertension. A Box–Behnken design was utilized to optimize the CAND-incorporated mixed polymeric micelles formulation (CAND-PFLC) consisting of Pluronics (P123 and F68) and lecithin (LC). The optimized CAND-PFLC micelles formulation was characterized for size, shape, zeta potential, polydispersity index (PDI), and entrapment efficiency (�). An in vitro release study, ex vivo permeability investigation, and an in vivo pharmacokinetic analysis were carried out to evaluate the performance of the formulation. The optimized CAND-PFLC micelles formulation demonstrated a spherical shape, a particle size of 44 ± 2.03 nm, a zeta potential of −7.07 ± 1.39 mV, a PDI of 0.326 ± 0.06, and an entrapment efficiency of 87 ± 3.12%. The formulation exhibited excellent compatibility, better stability, and a noncrystalline nature. An in vitro release study revealed a faster drug release of 7.98% at gastric pH in 2 hrs and 94.45% at intestinal pH within 24 hrs. The ex vivo investigation demonstrated a significantly enhanced permeability of CAND, with 94.86% in the micelle formulation compared to 9.03% of the pure drug. In vivo pharmacokinetic analysis showed a 4.11-fold increase in oral bioavailability of CAND compared to the marketed formulation. The CAND-PFLC mixed micelle formulation demonstrated improved performance compared to pure CAND, indicating its potential as a promising oral drug delivery system for the effective treatment of hypertension.</p

Silk Fibroin–Sodium Dodecyl Sulfate Gelation: Molecular, Structural, and Rheological Insights

A gelling agent is necessary to accelerate sol to gel transition in an aqueous solution of silk fibroin (SF), which otherwise takes several days to complete. In this paper, we investigate the mechanism of gelation of Bombyx mori SF by a model anionic surfactant, sodium dodecyl sulfate (SDS). Even though interactions between SDS and proteins have been extensively investigated, most of these studies have focused on globular proteins, which undergo denaturation. The interaction with a fibrous protein such as SF is different and results in an altered secondary structure leading to gelation. In this work, the concentration-dependent gelation process of the SF-SDS system is examined using rheology, SANS, FTIR, and NMR. We observed preferential binding of SDS to specific regions on the SF chain, which aids structural changes favoring β-sheet formation. We propose a mechanism for the accelerated sol–gel transition in the SF-SDS system

Discerning the Structure Factor of Charged Micelles in Water and Supercooled Solvent by Contrast Variation X‑ray Scattering

Sodium dodecyl sulfate (SDS) is a well-known anionic surfactant that forms micelles in various solvents including supercooled sugar–urea melt. Here, we explore the application of contrast variation small-angle X-ray scattering (SAXS) in discerning the structure and interactions of SDS micelles in aqueous solution and in a room-temperature supercooled solvent. The SAXS patterns can be analyzed in terms of a core–shell ellipsoid model. For aqueous SDS micelles, at low volume fractions, the features due to intermicellar interaction, S(q), in the SAXS pattern are poorly resolved because of the prominent contribution from shell scattering. Increasing the electron density of the solvent by the addition of the urea or fructose–urea mixture (at a weight ratio of 6:4) permits the systematic variation of shell scattering without influencing the structure drastically. For a 10% solution of SDS in water, the contribution from the shell can be completely masked by the addition of 40% urea or fructose–urea mixture. The fructose–urea mixture is a preferred additive as it can vary the scattering length density over a wide range and serves as a matrix to form supercooled micelles. The structural parameters of micelles in supercooled fructose–urea melt are obtained from contrast variation SAXS, small-angle neutron scattering, and high-resolution transmission electron microscopy

Rationalizing the Design of Pluronics–Surfactant Mixed Micelles through Molecular Simulations and Experiments

Aqueous systems comprising polymers and surfactants are technologically important complex fluids with tunable features dependent on the chemical nature of each constituent, overall composition in mixed systems, and solution conditions. The phase behavior and self-assembly of amphiphilic polymers can be changed drastically in the presence of conventional ionic surfactants and need to be clearly understood. Here, the self-aggregation dynamics of a triblock copolymer (Pluronics L81, EO3PO43EO3) in the presence of three cationic surfactants (with a 12C long alkyl chain but with different structural features), viz., dodecyltrimethylammonium bromide (DTAB), didodecyldimethylammonium bromide (DDAB), and ethanediyl-1,2-bis(dimethyldodecylammonium bromide) (12-2-12), were investigated in an aqueous solution environment. The nanoscale micellar size expressed as hydrodynamic diameter (Dh) of copolymer–surfactant mixed aggregates was evaluated using dynamic light scattering, while the presence of a varied micellar geometry of L81–cationic surfactant mixed micelles were probed using small-angle neutron scattering. The obtained findings were further validated from molecular dynamics (MD) simulations, employing a simple and transferable coarse-grained molecular model based on the MARTINI force field. L81 remained molecularly dissolved up to ∼20 °C but phase separated, forming turbid/translucent dispersion, close to its cloud point (CP) and existed as unstable vesicles. However, it exhibited interesting solution behavior expressed in terms of the blue point (BP) and the double CP in the presence of different surfactants, leading to mixed micellar systems with a triggered morphology transition from unstable vesicles to polymer-rich micelles and cationic surfactant-rich micelles. Such an amendment in the morphology of copolymer nanoaggregates in the presence of cationic surfactants has been well observed from scattering data. This is further rationalized employing the MD approach, which validated the effective interactions between Pluronics–cationic surfactant mixed micelles. Thus, our experimental results integrated with MD yield a deep insight into the nanoscale interactions controlling the micellar aggregation (Pluronics-rich micelles and surfactant-rich micelles) in the investigated mixed system

Biophysical and molecular modeling evidences for the binding of sulfa molecules with hemoglobin

The molecular mechanism of the heme protein, hemoglobin (Hb) interaction with sulfa molecule, sulfadiazine (SDZ) has been investigated through spectroscopic, neutron scattering and molecular modeling techniques. Absorption and emission spectroscopic studies showed that SDZ molecules were bound to Hb protein, non-cooperatively. The binding affinityof SDZ-Hb complex at standard experimental condition was evaluated to be around (4.2 ± 0.07) ×104, M−1with 1:1 stoichiometry. Drug induced structural perturbation of the 3 D protein moiety was confirmed through circular dichroism (CD), synchronous fluorescence and small angle neutron scattering methods. From the temperature dependent spectrofluorometric studies, the negative standard molar Gibbs energy change suggested the spontaneity of the reaction. The negative enthalpy and positive entropy change(s) indicated towards the involvement of both electrostatic and hydrophobic forces during the association process. Salt dependent fluorescence study revealed major contributions from non-poly-electrolytic forces. Molecular modeling studies determined the probable binding sites, types of interaction involved and the conformational alteration of the compactness of the Hb structure upon interaction with SDZ molecule. Overall, the study provides detailed insights into the binding mechanism of SDZ antibiotics to Hb protein. Communicated by Ramaswamy H. Sarma</p