Additive-anchored thermoresponsive nanoscale self-assembly generation in normal and reverse Tetronics®.

Self-assembly of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers (BCPs) in the presence of different kinds of additives is investigated in an aqueous solution environment. Commercially available four-armed BCPs, namely Tetronics® (normal: T904 with EO as the terminal end block; and reverse: T90R4 with PO as the terminal end block), each with 40%EO, are used. The effect of various additives such as electrolytes (NaCl and Na2SO4), nonelectrolyte polyols (glucose and sorbitol), and ionic surfactants (viz. anionic-sodium dodecyl sulfate (SDS), cationic-dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecyldimethylammonium propane sulfonate (C12PS)) on these BCPs is examined to observe their influence on micellization behaviour. The presence of salts and polyols displayed interesting phase behaviour, i.e., the cloud point (CP) was decreased, the water structure was affected and the micelles were dehydrated by expelling water molecules, and thus they were likely to promote micelle formation/growth. In contrast, ionic surfactants in small amounts interacted with the BCPs and showed an increase in CPs thereby forming mixed micelles with increasing charges and decreasing micellar sizes, finally transforming to small surfactant-rich mixed micelles. Molecular interactions such as electrostatic and hydrogen bonding involved within the examined entities are put forth employing a computational simulation approach using the Gaussian 09 window for calculation along with the GaussView 5.0.9 programming software using the (DFT)/B3LYP method and 3-21G basis set. The hydrodynamic diameter (Dh) of the micelles is examined using dynamic light scattering (DLS), while the various micellar parameters inferring the shape/geometry are obtained using small-angle neutron scattering (SANS) by the best fitting of the structure factors. It is observed that 10 w/v% T904 remains as spherical micelles with some micellar growth under physiological conditions (37 °C), while 10 w/v% T90R4 remains as unimers and forms spherical micelles in the presence of additives at 37 °C. Furthermore, the additive-induced micellar systems are tested as developing nanovehicles for anticancer (curcumin, Cur) drug solubilization using UV-vis spectroscopy, which shows a prominent increase in absorbance with enhanced solubilization capacity. Additionally, the cytotoxic effect of Cur loaded on the BCP micelles in HeLa cells is studied through confocal microscopy by capturing fluorescence images that depict HeLa cell growth inhibition under the influence of additive-induced micellar systems.

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

OBJECTIVE: 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. METHODS: 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 (%EE). 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. RESULTS: 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. CONCLUSION: 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.

Molecular insights into the aggregation and solubilizing behavior of biocompatible amphiphiles Gelucire® 48/16 and Tetronics® 1304 in aqueous media.

A comparative analysis of the micellar and solubilizing properties of two polyethylene glycol (PEG)-based amphiphilic biocompatible excipients: Gelucire® 48/16 (Ge 48/16) and Tetronics® 1304 (T1304), in the presence and absence of salt, was conducted. As there is a dearth of research in this area, the study aims to shed light on the behavior of these two nonionic surfactants and their potential as nanocarriers for solubilizing pharmaceuticals. Various techniques such as cloud point (CP), dynamic light scattering (DLS), small-angle neutron scattering (SANS), Fourier transform infrared spectroscopy (FT-IR), UV spectrophotometry, and high-performance liquid chromatography (HPLC) were employed. The solubility of quercetin (QCT), a flavonoid with anti-inflammatory, antioxidant, and anti-cancer properties, was evaluated and the interaction between QCT and the micellar system was examined. The analysis revealed the occurrence of strong interactions between QCT and surfactant molecules, resulting in enhanced solubility. It was observed that the micellar size and solubilizing ability were significantly improved in the presence of salt, while the CP decreased. Ge 48/16 exhibited superior performance, with a remarkable increase in the solubility of QCT in the presence of salt, suggesting its potential as an effective nanocarrier for a range of pharmaceutics, and yielding better therapeutic outcomes.

Salt induced micellization conduct in PEO-PPO-PEO-based block copolymers: a thermo-responsive approach.

The nanoscale self-assembly behavior in ethylene oxide (EO) and propylene oxide (PO)-based block copolymers (BCPs) commercially available as Pluronics®: L44 (PEO10-PPO23-PEO10) and F77 (PEO53-PPO34-PEO53) is put forth in aqueous solution and in the presence of sodium salts NaCl and Na2SO4. The moderate hydrophilicity of L44 is attributed to its low molecular weight PPO segment, while the high percentage of PEO content in F77 contributes to its extreme hydrophilicity. The impact of sodium salts (NaCl and Na2SO4) on the self-assembly is investigated to understand their influence and role in micellization, by employing various physicochemical techniques such as phase behavior conduct, calorimetry, tensiometry, scattering, and spectral analysis. The results indicate that at a low temperature range of 20-30 °C, Pluronics® solutions with a concentration of 10% w/v remain molecularly dissolved as individual units called unimers (Gaussian chain), which have a hydrodynamic size (Dh) of approximately 4-6 nm. Additionally, loose clusters of a few hundred nanometers in size are also observed. Though, at higher concentrations of BCPs and in the presence of salt or elevated temperatures, the examined micellar structures exhibit a higher degree of organization i.e., spherical or ellipsoidal in terms of size and shape. Also, the solubilization enhancement of a hydrophobic dye called orange OT within the examined micellar system is also undertaken using a spectral approach.

Nucleation-Growth Versus Spinodal Decomposition in Fe-Cr Alloys: An Experimental Verification by Atom Probe Tomography and Small Angle Neutron Scattering.

Identifying the operative mode of phase separation [spinodal decomposition (SD) or nucleation-growth (NG)] remains an extremely important area of research. The present work examines this critically in the Fe-Cr system using atom probe tomography (APT) and small angle neutron scattering (SANS), and establishes the framework to distinguish the two different modes of α' phase separation in thermally aged Fe-35 at% Cr and Fe-20 at% Cr alloys. Independent APT analysis determines the mode of phase separation on the basis of (i) the presence/absence of periodic chemical fluctuation through radial distribution function analysis and (ii) interphase interface characteristics (diffuse/sharp). SANS analysis, in contrast, yields virtually indistinguishable correlation peaks for both the modes, which necessitates further investigation of the several different aspects of SANS profiles in the light of APT results. For the first time, key features of SANS profiles have been identified that can unambiguously distinguish SD from NG in the Fe-Cr system: (i) nature of temporal evolution of FWHM of the correlation peak and (ii) appropriate value of γ for fitting with the dynamic scaling model (γ = 6 for SD, Fe-35 at% Cr alloy; γ = 4 for NG, Fe-20 at% Cr alloy).

Multiple Carbon Morphologies Derived from Polyion Complex-Based Double Hydrophilic Block Copolymers as Templates and Phenol as a Carbon Precursor.

This study demonstrates the multiple carbon morphology forming abilities of two dissimilar polyion complex (PIC)-based double hydrophilic block copolymers (DHBC) along with three different phenol concentrations when subjecting the blend in aqueous media via a hydrothermal-assisted carbonization strategy. The morphological transition from worm-like to spherical along with granular is found for the blend of oppositely charged poly(ethylene glycol) (PEG)-conjugated poly(amino acid) block copolymers, PEG-poly(l-lysine) (PEG-PLys) and PEG-poly(glutamic acid) (PEG-PGlu), along with three different concentrations of phenol. In contrast, after mixing the combination of PEG-PLys and PEG-poly(aspartic acid) (PEG-PAsp) separately with three different phenol contents, elliptical to irregular to spherical structural transition occurred. Fourier transform infrared and circular dichroism spectroscopic studies indicated that the formation of worm-like hybrid micellar structures is attributed to the presence of the ß-sheet structure, whereas spherical-shaped hybrid micellar structures are formed due to the existence of α-helix and random coil structures. We discuss the mechanism for the secondary structure-induced morphology formation based on the theory related to the packing parameter, which is commonly used for analyzing the shape of the micellar structures. Secondary structures of the PIC-based DHBC system are responsible for forming multiple carbon morphologies, whereas these structures are absent in the case of the amphiphilic block copolymer (ABC) system. Furthermore, ABC-based template methods require organic solvent, ultrasonication, and a prolonged solvent evaporation process to obtain multiple carbon morphologies. Scanning electron microscopy observations suggested there is no significant morphological change even after subjecting the hybrid micelles to carbonization at elevated temperatures. Raman scattering studies revealed that the degree of graphitization and the graphitic crystallite domain size of the carbonized sample depend on the phenol content. Carbon materials exhibited the highest specific surface area of 579 m2 g-1 along with a pore volume of 0.398 cc g-1, and this observation suggests that the prepared carbons are porous. Our findings illustrate the facile and effective strategy to fabricate the multiple carbon morphologies that can be used as potential candidates for energy storage applications.

A prospective hospital-based study on C-reactive protein as a response predictor of antidepressant treatment in drug naïve patients with major depressive disorder.

Background: C-reactive protein (CRP) is an acute phase reactant that is implicated in the pathogenesis of major depressive disorder (MDD), due to its role in the execution of various important neurological events, including neurogenesis, mediation of neural plasticity, and synaptic transmission. Aims: This study was conducted to determine the relationship between the level of CRP to remission rates after antidepressant therapy. Methods: Fifty patients of first episode MDD with no past history of antidepressant exposure and other medical comorbidity were recruited after obtaining consent for Escitalopram therapy. The CRP levels of the patients were evaluated on the day of recruitment and depressive symptoms were monitored using Montgomery-Asberg Depression Rating Scale at weeks 0, 3, 6, and 12. The patients with low (≤10 mg/l) and high (>10 mg/l) CRP levels were compared for time taken to achieve remission using Kaplan-Meier survival analysis. Results: The Kaplan-Meier survival analysis showed a significantly higher proportion of patients with low CRP levels attained remission than patients with higher CRP levels (Log-rank = 7.594; dF = 1; P = 0.006). The age, compliance to pharmacotherapy, and disability did not significantly affect the remission rates of the patients. Conclusion: Our study confirms that higher levels of CRP can lead to poorer remission rates in patients with MDD after antidepressant therapy and can predict treatment resistance.

Structural Changes in Liposomal Vesicles in Association with Sodium Taurodeoxycholate.

Liposomes composed of soy lecithin (SL) have been studied widely for drug delivery applications. The stability and elasticity of liposomal vesicles are improved by incorporating additives, including edge activators. In this study, we report the effect of sodium taurodeoxycholate (STDC, a bile salt) upon the microstructural characteristics of SL vesicles. Liposomes, prepared by the thin film hydration method, were characterized by dynamic light scattering (DLS), small-angle neutron scattering (SANS), electron microscopy, and rheological techniques. We noticed a reduction in the size of vesicles with the incremental addition of STDC. Initial changes in the size of spherical vesicles were ascribed to the edge-activating action of STDC (0.05 to 0.17 µM). At higher concentrations (0.23 to 0.27 µM), these vesicles transformed into cylindrical structures. Morphological transitions at higher STDC concentrations would have occurred due to its hydrophobic interaction with SL molecules in the bilayer. This was ascertained from nuclear magnetic resonance observations. Whereas shape transitions underscored the deformability of vesicles in the presence of STDC, the consistency of bilayer thickness ruled out any dissociative effect. It was interesting to notice that SL-STDC mixed structures could survive high thermal stress, electrolyte addition, and dilution.

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.

Application of Drug Aggregation to Solubilize Antimicrobial Compound and Enhancing its Bioavailability.

With the progress and advancement in discovery of novel antimicrobial drugs, efficient solubility plays an important component for a drug to express its out-turn effectively. A biocompatible neutral/non-ionic surfactant, Triton X-100 (Tx-100), was successfully employed to solubilize an antibiotic drug, sulfamethazine (SMZ), through micellization process. The association process of Tx-100 toward SMZ was confirmed through the characteristic spectral change in absorption and emission spectroscopy. The morphological behavior of the complex was studied from small angle neutron scattering (SANS). Changes in size(s) and charge(s) of the micelles were monitored using zeta (z) potential technique. This present study emphasized the molecular mechanism and characteristics of Tx-100 as an effective drug solubilizing and carrier agent. Thus, the drug-loaded micellar system can enhance cellular uptake and increase the antibacterial effects of drugs in the biological system(s). Schematic illustration of drug-surfactant micelle formation and target release of drug at the targeted site.

Pectin self-assembly and its disruption by water: insights into plant cell wall mechanics.

Plant cell walls undergo multiple cycles of dehydration and rehydration during their life. Calcium crosslinked low methoxy pectin is a major constituent of plant cell walls. Understanding the dehydration-rehydration behavior of pectin gels may shed light on the water transport and mechanics of plant cells. In this work, we report the contributions of the microstructure to the mechanics of pectin-Ca gels subjected to different extents of dehydration and subsequent rehydration. This is investigated using a pectin gel composition that forms 'egg-box bundles', a characteristic feature of the microstructure of low methoxy pectin-Ca gels. Large amplitude oscillatory shear (LAOS) rheology along with small angle neutron scattering and near infrared (NIR) spectroscopy on pectin gels is used to elucidate the mechanical and microstructural changes during dehydration-rehydration cycles. As the extent of dehydration increases, the reswelling ability, strain-stiffening behavior and yield strain decrease. These effects are more prominent at faster rates of dehydration and are not completely reversible upon rehydration to the initial undried state. Microstructural changes due to the aggregation of egg-box bundles and single chains and the associated changes in the water configurations lead to these irreversible changes.

Glucose-induced self-assembly and phase separation in hydrophilic triblock copolymers and the governing mechanism.

Poly(ethylene oxide, EO)-poly(propylene oxide, PO)-poly(ethylene oxide, EO)-based triblock copolymers (BCPs) with 80% hydrophilicity stay molecularly dissolved as Gaussian chains at ambient temperature, even at fairly high concentrations (>5 %w/v). This study presents the plausible micellization behaviour of such very-hydrophilic Pluronics® - F38, F68, F88, F98, and F108 - incited upon the addition of glucose at low concentrations and temperatures. The outcomes obtained from phase behaviour and scattering studies are described. At temperatures near to ambient temperature, these BCPs form micelles with a central core made of a PO block, surrounded by a corona of highly hydrated EO chains. The phase transitions in these hydrophilic Pluronics® in the presence of glucose are demonstrated via the dehydration of the copolymer coil, leading to a decrease in the I1/I3 ratio, as determined using fluorescence spectroscopy. The temperature-dependent cloud point (CP) showed a marked decrease with an increase in the PO molecular weight and also in the presence of glucose. The change in solution relative viscosity (ηrel) caused by glucose is due to the enhanced dehydration of the EO block of the BCP amphiphile. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) investigations suggested that the dimensions of the hydrophobic core increase during the dehydration of the EO-PO blocks upon a temperature increase or after adding varying concentrations of glucose, thereby resulting in a micellar shape transition. It has been observed that added glucose influences the phase behaviour of BCPs in an analogous way to the influence of temperature. Also, plausible interactions between the EO-PO blocks and glucose were suggested based on the evaluated optimized descriptors obtained from a computational simulation approach. In addition, the core-shell blended micelles obtained using these BCPs are successfully utilized for drug (curcumin, Cur) solubilization based on the observed peak intensities from UV-visible spectroscopy. The loading of Cur into glucose-containing and glucose-free hydrophilic Pluronic® micelles shows how the radius of the micellar core (Rc) increases in the presence of glucose, thereby indicating Cur solubility enhancement for the Pluronic® micelles. Various kinetics models were employed, demonstrating a drug release profile that enables this approach to be used as an ideal platform for drug delivery.

Micellar assembly leading to structural growth/transition in normal and reverse Tetronics® in single and mixed solution environment.

This study scrutinizes the self-association of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers as normal Tetronic® (T904) and reverse Tetronic® R (T90R4) with varying molecular characteristics and different hydrophilic-hydrophobic ratios in an aqueous solution environment. These thermo-responsive solutions appear clear, transparent or bluish up to 10%w/v, which anticipated the probable transition of unimers to spherical or ellipsoidal micelles which is complemented by scattering experiments. In a single-solution environment, 10%w/v T904 formed star-shaped micelles at ambient temperature and exhibited a micellar growth/transition with temperature ageing. While 10%w/v T90R4 exists as unimers or a Gaussian coil over a wide range of temperature. Very interestingly, close to the cloud point (CP) flower-shaped spherical and ellipsoidal micelles were formed. A similar proposed micellar scheme was also examined for mixed systems T904 : T90R4 in varying ratios (1 : 0, 3 : 1, 1 : 1, 1 : 3 and 0 : 1) giving an account to the solution behavior of the mixtures. An amalgamation of dynamic light scattering (DLS) and small-angle neutron scattering (SANS) techniques achieved the thorough extraction of the structural parameters of the micellar system. The hydrodynamic diameter (Dh) of the micelles with temperature variation was evaluated from dynamic light scattering (DLS) while the structure factor of the micelles was found by employing small-angle neutron scattering (SANS). Furthermore, the single and mixed micellar systems were quantitatively and qualitatively examined for anticancer drug solubilization using UV-vis spectroscopy for their superior use as potential nanocargos.

Multimodal Applications of Zinc Gallate-Based Persistent Luminescent Nanoparticles in Cancer Treatment: Tumor Margining, Diagnosis, and Boron Neutron Capture Therapy.

On the basis of the boron neutron capture therapy (BNCT) modality, we have designed and synthesized a zinc gallate (ZnGa2O4)-based nanoformulation for developing an innovative theranostic approach for cancer treatment. Initially, the (ZnGa1.995Cr0.005O4 or ZnGa2O4:(0.5%)Cr persistent luminescence nanoparticles (PLNPs) embedded on silica matrix were synthesized. Their surface functionalization was performed using organic synthesis strategies to attach the amine functional moieties which were further coupled with poly(vicinal diol). These diols were helpful for conjugation with 10B(OH)3, which subsequently served to couple with an in-house-synthesized variant of pH-(low)-insertion peptide (pHLIP) finally giving a tumor-targeting nanoformulation. Most importantly, the polymeric diols helped in conjugation of a substantial number of 10B to provide the therapeutic dose required for effective BNCT. This nanoformulation internalized substantially (∼80%) to WEHI-164 cancer cells within 6 h. Tumor homing studies indicated that the accumulation of this formulation at the acidic tumor site was within 2 h. The in vitro evaluation of the formulation against WEHI-164 cancer cells followed by neutron irradiation revealed its potent cytotoxicity with IC50 ∼ 25 µM. In the case of studies on animal models, the melanoma-induced C57BL/6 and fibrosarcoma-induced BALB/c mice were treated with formulations through intratumoral and intravenous injections, respectively, followed by neutron irradiation, leading to a significant killing of the cancer cells, which was evidenced by a reduction in tumor volume (75-80%) as compared with a control tumor. Furthermore, the histopathological studies confirmed a damaging effect only on tumor cells, while there was no sign of damage to the vital organs in treated mice as well as in controls.

Heme Protein Binding of Sulfonamide Compounds: A Correlation Study by Spectroscopic, Calorimetric, and Computational Methods.

Protein-ligand interaction studies are useful to determine the molecular mechanism of the binding phenomenon, leading to the establishment of the structure-function relationship. Here, we report the binding of well-known antibiotic sulfonamide drugs (sulfamethazine, SMZ; and sulfadiazine, SDZ) with heme protein myoglobin (Mb) using spectroscopic, calorimetric, ζ potential, and computational methods. Formation of a 1:1 complex between the ligand and Mb through well-defined equilibrium was observed. The binding constants obtained between Mb and SMZ/SDZ drugs were on the order of 104 M-1. SMZ with two additional methyl (-CH3) substitutions has higher affinity than SDZ. Upon drug binding, a notable loss in the helicity (via circular dichroism) and perturbation of the three-dimensional (3D) protein structure (via infrared and synchronous fluorescence experiments) were observed. The binding also indicated the dominance of non-polyelectrolytic forces between the amino acid residues of the protein and the drugs. The ligand-protein binding distance signified high probability of energy transfer between them. Destabilization of the protein structure upon binding was evident from differential scanning calorimetry results and ζ potential analyses. Molecular docking presented the best probable binding sites of the drugs inside protein pockets. Thus, the present study explores the potential binding characteristics of two sulfonamide drugs (with different substitutions) with myoglobin, correlating the structural and energetic aspects.

Formulation, Solubilization, and In Vitro Characterization of Quercetin-Incorporated Mixed Micelles of PEO-PPO-PEO Block Copolymers.

Quercetin (QCN) is a plant polyphenol with a variety of medicinal effects. Poor water solubility, on the other hand, restricts its therapeutic effectiveness. The purpose of this study was to develop mixed micellar systems using two biocompatible amphiphilic PEO-PPO-PEO triblock copolymers, Pluronic P123 (EO20-PO70-EO20) and Pluronic F88 (EO104-PO39-EO104), in order to enhance the aqueous solubility and oral bioavailability of QCN drug. The critical micelle concentrations (CMCs) of mixed P123/F88 micellar solutions were investigated using UV-visible spectroscopy with pyrene as a probe. Mixed P123/F88 micelles have low CMCs, indicating that they have a stable micelle structure even when diluted. The solubility of QCN in aqueous mixed P123/F88 micellar solutions at different temperatures was investigated to better understand drug entrapment. The QCN solubility increased with increasing temperature in the mixed P123/F88 micellar system. The QCN-incorporated mixed P123/F88 micelles were prepared using the thin-film hydration method and were well characterized in terms of size and morphology, compatibility, in vitro release and antioxidant profile. In addition, the cell proliferation activity of the mixed micelles was evaluated in the MCF-7 cell line. The QCN-incorporated mixed P123/F88 micelles had a small particle size (< 25 nm) and a negative zeta potential with a spherical shape. The in vitro release behaviour of QCN from a mixed P123/F88 micellar system was slower and more sustained at physiological conditions. The oxidation resistance of QCN-incorporating mixed P123/F88 micelles was shown to be considerably higher than that of pure QCN. An in vitro cell proliferation study revealed that QCN-incorporated mixed micells were effective in inhibiting tumour cell growth. In conclusion, the QCN-incorporated mixed P123/F88 micelle may be a promising approach to increase QCN oral bioavailability, antioxidant activity, and cell viability.

Tuning of silica nanoparticle-lysozyme protein complexes in the presence of the SDS surfactant.

The structures of the complexes of anionic silica nanoparticle (size ∼ 16 nm)-lysozyme (cationic) protein, tuned by the addition of the anionic surfactant sodium dodecyl sulfate (SDS), have been investigated by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). The unique advantage of contrast variation SANS has been used to probe the role of individual components in binary and ternary systems. The cationic lysozyme protein (at pH ∼ 7) adsorbs on the anionic silica nanoparticles and forms mass fractal aggregates due to the strong attractive interaction, whereas similarly charged SDS does not interact physically with silica nanoparticles. The presence of SDS, however, remarkably affects the nanoparticle-protein interactions via binding with the oppositely charged segments of lysozyme. In general, the SDS-lysozyme complexes possess a variety of structures (e.g., insoluble complexes of Ly(DS)8, crystalline structure, or micelle-like structure) depending on the surfactant-to-protein molar ratio (S/P). In the ternary system (HS40-lysozyme-SDS), lysozyme preferentially binds with SDS, instead of directly to nanoparticles. At low S/Ps (0 ≤ S/P ≤ 10), the SDS concentration is not enough to fully neutralize the charge of lysozyme, leading to the formation of cationic SDS-lysozyme complex-mediated nanoparticle aggregation. The morphology of the nanoparticle-(lysozyme-SDS) complexes is also found to be mass fractal kind where the fractal dimension increases with increasing SDS concentration. At S/P > 10, there is sufficient SDS to fully neutralize the lysozyme in the absence of competing charges from the particle but it is at S/P = 50 before all lysozyme desorbs from the particle and binds completely to the overwhelming amount of SDS, creating an oppositely charged lysozyme-SDS complex, which is repelled from the particle.

Single Amino-Acid Based Self-Assembled Biomaterials with Potent Antimicrobial Activity.

The design and development of soft biomaterials based on amino acid and short-peptide have gained much attention due to their potent biomedical applications. A slight alteration in the side-chain of single amino acid in a peptide or protein sequence has a huge impact on the structure and function. Phenylalanine is one of the most studied amino acids, which contains an aromatic phenyl group connected through a flexible -CH2 - unit. In this work, we have examined whether flexibility and aromatic functionality of phenylalanine (Phe) are important in gel formation of model gelator Fmoc-Phe-OH or not. To examine this hypothesis, we synthesized Fmoc-derivatives of three analogues unnatural amino acids including cyclohexylalanine, phenylglycine, and homophenylalanine; which are slightly varied from Phe. Interestingly, all these three new analogues formed hydrogels in phosphate buffer at pH 7.0 having different gelation efficacy and kinetics. This study suggests that the presence of aromatic side-chain and flexibility are not mandatory for the gelation of this model gelator. Newly synthesized unnatural amino acid derivatives have also exhibited promising antimicrobial activity towards gram-positive bacteria by inhibiting cellular oxygen consumption. We further determined the biocompatibility of these amino acid derivatives by using a hemolysis assay on human blood cells. Overall studies described the development of single amino acid-based new injectable biomaterials with improved antimicrobial activity by the slight alteration in the side-chain of amino acid.

Contrasting effect of 1-butanol and 1,4-butanediol on the triggered micellar self-assemblies of C16-type cationic surfactants.

The self-assembly in aqueous solutions of three quaternary salt-based C16-type cationic surfactants with different polar head groups and identical carbon alkyl chain viz., cetylpyridinium bromide (CPB), cetyltrimethylammonium tosylate (CTAT), and cetyltriphenylphosphonium bromide (CTPPB) in the presence of 1-butanol (BuOH) and 1,4-butanediol (BTD) was investigated using tensiometry, 2D-nuclear Overhauser enhancement spectroscopy (2D-NOESY) and small angle neutron scattering (SANS) techniques. The adsorption parameters and micellar characteristics evaluated at 303.15 K distinctly showed that BuOH promotes the mixed micelle formation while BTD interfered with the micellization phenomenon. The SANS data fitted using an ellipsoid (as derived by Hayter and Penfold using the Ornstein-Zernike equation and the mean spherical approximation) and wormlike micellar models offered an insight into the micelle size/shape and aggregation number (Nagg) in the examined systems. The evaluated descriptors presented a clear indication of the morphology transition in cationic micelles as induced by the addition of the two alcohols. We also offer an investigation into the acceptable molecular interactions governing the differences in micelle morphologies, using the non-invasive 2D-NOESY technique and molecular modeling. The experimental observations elucidated from computational simulation add novelty to this work. Giving an account to the structural complexity in the three cationic surfactants, the molecular dynamics (MD) simulation was performed for CPB micelles in an aqueous solution of alcohols that highlighted the micelle solvation and structural transition, which is further complemented in terms of critical packing parameter (PP) for the examined systems.