P. A. Hassan

Making Sense of Brownian Motion: Colloid Characterization by Dynamic Light Scattering

Dynamic light scattering (DLS) has evolved as a fast, convenient tool for particle size analysis of noninteracting spherical colloids. In this historical review, we discuss the basic principle, data analysis, and important precautions to be taken while analyzing colloids using DLS. The effect of particle interaction, polydispersity, anisotropy, light absorption, and so forth, on measured diffusion coefficient is discussed. New developments in this area such as diffusing wave spectroscopy, particle tracking analysis, microrheological studies using DLS, and so forth, are discussed in a manner that can be understood by a beginner.

Tween 80-sodium deoxycholate mixed micelles: structural characterization and application in doxorubicin delivery.

The objective of the present investigation is to develop and characterize anionic mixed micelles of two biocompatible surfactants, Tween 80 (T-80) and sodium deoxycholate (NaDC), and evaluate their potential in the delivery of doxorubicin hydrochloride (DOX), a cationic anticancer drug. The mixed micelles were characterized for their microstructure, intermicellar interactions, and doxorubicin binding ability by dynamic light scattering, small angle neutron scattering (SANS), viscosity, and optical absorption measurements. Salt-induced growth of the mixed micelles at different compositions suggests that both electrostatic interaction of the anionic bile salts and steric repulsion of the ethylene oxide groups in nonionic components are affected by the presence of electrolytes. Addition of bile salt molecules to T-80 micelles suppresses the salt-induced growth of nonionic T-80 micelles. SANS studies indicate that bile salt micelles are prolate ellipsoidal in shape, and the addition of T-80 transforms them toward a spherical shape. The anionic bile salt can successfully bind to the cationic drug doxorubicin. The in vitro cytotoxicity studies in various cancer cell lines revealed that DOX-loaded micelles have greater in vitro anticancer activity as compared to DOX solution, indicating their potential in pharmaceutical applications.

Viscoelastic micellar water/CTAB/NaNO3 solutions: Rheology, SANS and cryo-TEM analysis

Aqueous micellar solutions of the cationic surfactant hexadecyltrimethylammonium bromide (CTAB) and sodium nitrate (NaNO(3)) were examined using steady and dynamic rheology, small-angle neutron scattering (SANS) and cryogenic-transmission electron microscopy (cryo-TEM). Upon addition of NaNO(3), the CTAB spherical micelles transform into long, flexible wormlike micelles, conveying viscoelastic properties to the solutions. The zero-shear viscosity (eta(0)) versus NaNO(3) concentration curve exhibits a well-defined maximum. Likewise, upon increase in temperature, the viscosity decreases. Dynamic rheological data of the entangled micellar solutions can be well described by the Maxwell model. Changes in the structural parameters of the micelles with addition of NaNO(3) were inferred from SANS measurements. The intensity of scattered neutrons at the low q region was found to increase with increasing NaNO(3) concentration. This suggests an increase in size of the micelles and/or decrease of intermicellar interactions with increasing salt concentration. Analysis of the SANS data using prolate ellipsoidal structure and Yukawa form of interaction potential between micelles indicates that addition of NaNO(3) leads to a decrease in the surface charge of the ellipsoidal micelles and consequently an increase in their length. The structural transition from spherical to entangled threadlike micelles, induced by the addition of NaNO(3) to CTAB micelles is further confirmed by cryo-TEM.

Lecithin-Based Novel Cationic Nanocarriers (Leciplex) II: Improving Therapeutic Efficacy of Quercetin on Oral Administration†

The objective of the present investigation was to evaluate ability of the novel self-assembled phospholipid- based cationic nanocarriers (LeciPlex) in improving the therapeutic efficacy of a poorly water-soluble natural polyphenolic agent, quercetin (QR), on oral administration. Quercetin loaded LeciPlex (QR-LeciPlex) were successfully fabricated using a biocompatible solvent Transcutol HP. The QR-LeciPlex were characterized for particle size, encapsulation efficiency, zeta potential, and particle morphology by cryo-TEM. UV and fluorescence spectral characterization was carried out to find out the association of QR with LeciPlex. Small angle neutron scattering studies (SANS) were carried out to understand the internal structure of Leciplex and to evaluate the influence of the incorporation of QR in the LeciPlex. Anti-inflammatory and antitumorigenic activity of QR-LeciPlex was determined in comparison to QR suspension to evaluate the potential of LeciPlex in improving oral delivery of QR. QR-LeciPlex exhibited a particle size of ∼400 nm and had excellent colloidal stability. The QR-LeciPlex had a zeta potential greater than +30 mV and exhibited very high encapsulation efficiency of QR (>90%). UV and fluorescence spectral characterization indicated the interaction/association of QR with LeciPlex components. Cryo-TEM studies showed that LeciPlex and QR-LeciPlex have a unilamellar structure. SANS confirmed the unilamellar structure of LeciPlex and indicated that the incorporation of QR does not have any effect on the internal structure of the LeciPlex. QR-LeciPlex exhibited significantly higher anti-inflammatory and antitumorigenic activity (p < 0.01) as compared to that of QR suspension on oral administration.

pH-Responsive self-assembly in an aqueous mixture of surfactant and hydrophobic amino acid mimic

The pH-responsive behavior of an amino acid is used to control the electrostatic interactions on a cationic micelle surface and thereby alter the morphology of self-assembled structures formed by them. The pH-induced changes in the rheology and microstructure in an aqueous mixture of cetyltrimethyl ammonium bromide (CTAB) and a hydrophobic amino acid mimic, anthranilic acid (AA) were studied by rheological measurements, small-angle neutron scattering (SANS) and light scattering. At low pH, when the net charge on the amino acid is positive, nearly globular mixed micelles are formed. With increase in pH, the AA becomes negatively charged due to the dissociation of carboxyl group and complexes with the positively charged CTAB molecule. This electrostatic complexation decreases the surface charge of the micelles, leading to a structural evolution from small globular micelles to long worm-like assemblies. Rheological studies indicate a transition from Newtonian to viscoelastic nature of the fluid with an increase in the pH of the solution. SANS studies confirm the formation of prolate ellipsoidal micelles and the axial ratio of the micelle increases with an increase in pH of the solution. The variation in the diffusion coefficient of the micelles with pH is consistent with the SANS results. This demonstrates the use of hydrophobic amino acids in creating pH-sensitive assemblies of amphiphiles. An increase in the zero shear viscosity of the fluid of four orders of magnitude could be achieved by a slight change in the pH of the solution.

Carboxyl decorated Fe3O4 nanoparticles for MRI diagnosis and localized hyperthermia

We report the development of carboxyl decorated iron oxide nanoparticles (CIONs) by a facile soft-chemical approach for magnetic resonance imaging (MRI) and hyperthermia applications. These superparamagnetic CIONs (~10 nm) are resistant to protein adsorption under physiological medium and exhibit good colloidal stability, magnetization and cytocompatibility with cell lines. Analysis of the T2-weighted MRI scans of CIONs in water yields a transverse relaxivity (r2) value of 215 mM(-1) s(-1). The good colloidal stability and high r2 value make these CIONs as promising candidates for high-efficiency T2 contrast agent in MRI. Further, these biocompatible nanoparticles show excellent self-heating efficacy under external AC magnetic field (AMF). The infrared thermal imaging confirmed the localized heating of CIONs under AMF. Thus, these carboxyl decorated Fe3O4 nanoparticles can be used as a contrast agent in MRI as well as localized heat activated killing of cancer cells. Furthermore, the active functional groups (COOH) present on the surface of Fe3O4 nanoparticles can be accessible for routine conjugation of biomolecules/drugs through well-developed bioconjugation chemistry.

Dilution induced thickening in hydrotrope-rich rod-like micelles

Dilution induced changes in the microstructure and rheological behavior of micelles formed by a cationic surfactant-anionic hydrotrope mixture has been investigated in the hydrotrope-rich region. The surfactant used is cetyltrimethylammonium bromide (CTAB) and the hydrotropic salt is sodium 3-hydroxy naphthalene 2-carboxylate (SHNC). The concentration of the mixture is varied from 0.5% to 10.0% w/w (φ=0.005-0.100) at a fixed weight ratio of hydrotrope to surfactant (85:15). Rheological studies indicate Newtonian flow behavior at low and high volume fractions (0.005 and 0.100) while a shear thinning behavior is observed at intermediate volume fractions. The zero-shear viscosity η(0) also passes through a maximum upon changes in the concentration. The most striking feature in our study is that a low viscosity Newtonian fluid transforms to a viscoelastic fluid, upon dilution, and then again to a Newtonain fluid. Small angle neutron scattering studies of 10.0% micellar solution show the presence of rod-like aggregates. Upon dilution, the scattering intensity per unit concentration shows an increase in the low q-region. The nature of pair distance distribution function and subsequent model fitting indicates a transition from rod-like micelles to unilamellar vesicles upon dilution. This behavior is explained in terms of the volume fraction dependant solubilization of hydrotropes in the rod-like micelles and consequent changes in the composition of the mixed micelles.

Nanocomposite silica surfactant microcapsules by evaporation induced self assembly: tuning the morphological buckling by modifying viscosity and surface charge

Nanocomposite microcapsules of silica and surfactants have been synthesized using evaporation induced self-assembly through spray drying. It was established using electron microscopy and small-angle neutron/X-ray scattering experiments that the viscosity of the virgin dispersion and surface charge of colloidal components play a significant role in the buckling of spray droplets during drying. Hollow spherical grains are realized at relatively low viscosity and higher surface charge while mushroom like grains manifest at higher viscosity and lower surface charge. In the intermediate conditions, deformed doughnut shaped microcapsules are obtained. Scattering experiments establish the presence of the organization of micelle like aggregates of surfactants in the dried grains and also corroborate with the observations from electron microscopy. A plausible mechanism regarding the chronological pathways of morphological transformation is illustrated. Computer simulation, based on buckling of an elastic shell using a surface evolver, has been attempted in order to corroborate the experimental results.

Pluronic L64 Micelles near Cloud Point: Investigating the Role of Micellar Growth and Interaction in Critical Concentration Fluctuation and Percolation

The structure and the properties of the (Ethylene Oxide)(13)(Propylene Oxide)(30)(Ethylene Oxide)(13) (Pluronic L64, MW approximately 2900) micelles have been studied in the aqueous medium by small angle neutron scattering (SANS), dynamic light scattering (DLS) and viscometry measurements. The aqueous solutions of this triblock copolymer are unique among the pluronic solutions in showing critical concentration fluctuations and a concomitant enhancement in viscosity on approaching their cloud point. So far these results have been attributed solely to the presence of attractive interaction between the spherical L64 micelles. Recent theoretical studies, on the other hand, suggest that L64 micelles prefer a prolate ellipsoidal structure to sphere (Bedrov et al. Langmuir 2007, 23, 12032) and have a predominantly repulsive intermicellar interaction. A comparative analysis of our SANS data based on the spherical and prolate ellipsoidal structure shows that the L64 micelles can be best described by a prolate ellipsoidal structure, the aspect ratios of which increase progressively with increase in temperature. This, together with our viscosity and DLS studies, suggests that the enhanced viscosity of the copolymer solution near the cloud point arises largely due to the anisotropic growth of the micelles to the worm-like structures. The role of the intermicellar attractive interaction has thus been limited to the observed critical concentration fluctuation, and its effect decreases progressively with increase in copolymer concentration. It has also been shown that the water structure making salts like NaCl reduces the micellar growth temperature and helps in forming worm-like micelles at the room temperature. These studies thus identify the effect of micellar growth and interaction in determining the properties of the copolymer solution near the cloud point, which are the first of its kind in the case of the pluronics.

Time Dependent Sphere-to-Rod Growth of the Pluronic Micelles: Investigating the Role of Core and Corona Solvation in Determining the Micellar Growth Rate

The salt induced sphere-to-rod growth in the micelles of the PEO-PPO triblock copolymers, Pluronic P123 (EO(20)PO(70)PEO(20)) and Pluronic P103 (EO(16)PO(61)PEO(16)), has been studied by dynamic light scattering (DLS), viscometry, and small angle neutron scattering (SANS) techniques. The observed micellar growths are found to be time dependent and have a strong variation in their growth rate with changing anion type and copolymer composition. The rate of growth increases rather significantly with an increase in the water structure making abilities of the anions along the Hofmeister series in the order Cl(-) < F(-)< (PO(4))(3-). This has been attributed to an increasing ability of these ions to dehydrate the micellar corona, a factor that plays an important role in inducing sphere-to-rod shape transition of the micelles. The copolymer composition also has a significant influence on the micellar growth rate, as the P103 with a smaller molecular weight than P123 shows a significantly faster growth of its micelles under similar conditions. The observed time dependence in micellar growth in these systems has been attributed to a slow micellar restructuring process necessary to attain the equilibrium structure of the micelles. A remarkable improvement in the growth rate of the micelles, however, could be achieved in the presence of ethanol, a solvent that has affinity toward both the PPO and PEO blocks. Our spectroscopic studies suggest that the observed improvement in the micellar growth rate by ethanol is due to an accelerated restructuring process of the micelles in the presence of the solvated micellar core. These studies thus highlight the role of changing core and corona solvation characteristics of the pluronic micelles in determining their rearrangement and the growth rate, which is first of its kind in the aqueous pluronic system.