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Delivery is the key challenge for siRNA based therapeutics. Here, we report the development of new poly(glycoamidoamine) brush nanomaterials for efficient siRNA delivery. GluN4C10 polymer brush nanoparticles, a lead material, demonstrated significantly improved delivery efficiency for siRNA against factor VII (FVII) in mice compared to poly(glycoamidoamine) brush nanomaterials reported previously.

Addition of the hydrotropic salt sodium tosylate (TSNa) to solutions of a polymerizable cationic surfactant, methacryloyloxyundecyltrimethylammonium bromide (MUTB), leads to a transition from spherical to wormlike micelles about 40 nm in length. The wormlike micelles were successfully polymerized to yield stable, single-phase solutions of polymerized micelles. The polymerized wormlike micelles were several hundred nanometers long, although their cross-sectional radius remained unchanged (~2 nm). The spherical to wormlike micelle transition, and the wormlike micelles polymerized at different molar ratios of TSNa to MUTB, were characterized using quasi-elastic and static light scattering, small-angle neutron scattering, NMR, and cryogenic transmission electron microscopy.

Polymeric prodrugs of mPEG−PLA−haloperidol (methoxypoly(ethylene glycol)-b-poly(lactic acid)) can self-assemble into nanoscale micelle-like structures in aqueous solutions. mPEG−PLA−haloperidol was prepared and characterized using ¹H and ¹³C NMR. The conjugation efficiency was found to be 64.8 ± 21%. Micelles that form spontaneously upon solubilization of the mPEG−PLA and the polymeric prodrugs in water were characterized using a variety of techniques. The mPEG−PLA and prodrug micelles were found to have diameters of 28.73 ± 1.45 and 49.67 ± 4.29 nm, respectively, using dynamic light scattering (DLS). The micelle size and polydispersity were also evaluated with cryogenic transmission electron microscopy (cryo-TEM) and were consistent with the DLS results. Cryo-TEM and proton NMR confirmed that the micelles were spherical in shape. DLS was also used to determine the aggregation numbers of the micelles. The aggregation numbers ranged from 351 to 603. The change in aggregation number was dependent on the total drug incorporation into the micelle core. Critical micelle concentrations were determined for the various micelle/drug formulations and found to range from 3 to 14 μg/mL. Finally, drug was incorporated into the micelle core using the conjugate, free drug with a saturated aqueous phase during production, or a combination of both techniques. Drug incorporation could be increased from 3% to 20% (w/w) using the different formulations.

Unexpected colloidal assemblies form in aqueous mixtures of sodium dodecylbenzenesulfonate (SDBS) with the following imidazoline compounds:  2,2‘-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (V-44, which is a commonly used free-radical initiator), 2,2‘-tetramethylenedi-2-imidazoline (TMI), and the main recombination product (RP) from the decomposition of V-44. All of these imidazoline compounds act as hydrotropes. As the molar ratio of imidazoline to SDBS increases, a gradual transition from micelles to vesicles to bilayers to precipitate is observed. V-44 decomposes slowly at 25 °C, and the phase diagrams of V-44/SDBS and RP/SDBS are similar. The vesicular region observed in mixtures of TMI/SDBS is larger in composition than that of V-44/SDBS and RP/SDBS mixtures. At equimolar compositions of SDBS and RP, a novel colloidal structure with multiple closely packed bilayers is observed. In these mixtures, small unilamellar vesicles (<80 nm in diameter) form spontaneously, although with time they coexist with a small amount of precipitate and their size increases steadily. The self-assembly of vesicles occurs over a wide range of compositions when the solution pH is lower than the pKa of the imidazoline moiety. Quasi-elastic light scattering, cryogenic transmission electron microscopy, nuclear magnetic resonance, and small-angle neutron scattering were used to determine the characteristic length scales and properties of the assemblies.

The synthesis, phase behavior, and mixing properties of cationic dimeric (gemini) surfactants having one or two perfluoroalkyl chains is described and compared to that of analogue hydrocarbon surfactants. The combination of the dimeric character of the amphiphiles with the high hydrophobicity of the fluorocarbon chains leads to very low critical micelle concentration values and unusually low characteristic times of exchange between surfactants in the bulk solution and surfactants in the aggregate. This results in slow exchange on the NMR time scale, which allows a practical study of micellization and comicellization by NMR. With respect to the morphology of the aggregates, the fluorocarbon amphiphiles do not simply behave as more hydrophobic amphiphiles. Instead, they assemble into various structures including very stable unilamellar and multilamellar vesicles not seen in their hydrocarbon analogues. The hybrid hydrocarbon−fluorocarbon dimeric surfactant exhibits features of both families. In particular it mixes with either hydrocarbon or fluorocarbon surfactants, whereas the latter two undergo a macroscopic phase separation.

The evolution of the droplet size distribution of a tetradecane in water emulsion, stabilized by sodium dodecyl benzene sulfonate (SDBS) was followed by cryo-TEM during a 51 day period. As a reference for the initial distribution of a freshly prepared emulsion, the size distribution of a virtually nongrowing squalane in water emulsion was also monitored. It appears that the initial distribution is right skewed and close to log-normal with a broadness parameter of σ = 0.5. This distribution evolved rapidly to a more symmetrical one. At the end of the observation the average particle size increased by a factor of about 2.5, but the limiting left skewed distribution, predicted by the LSW (Lifshitz−Slyozov−Wagner) theory, was not obtained. The ripening rate estimated from the slope of an³ (an is the number averaged radius) as a function of time is in agreement with the prediction from the LSW theory.

The mixed micellization between cetyltrimethylammonium bromide (CTAB) and the anionic dimeric surfactant disodium 1,11-didecyl-3,6,9-trioxaundecane)-1,11-disulfate (2) has been investigated by electrical conductivity (Krafft temperature, TK, critical micellization concentration, cmc, and micelle ionization degree), spectrofluorometry (cmc, micelle polarity), time-resolved fluorescence quenching (micelle aggregation numbers), and transmission electron microscopy at cryogenic temperature (microstructure of the system) in water + 50 mM NaBr. Most measurements were performed at a CTAB concentration of 5 mM, a mole fraction of 2 X = 0.091, and 30 °C. Some measurements were performed in pure water for assessing the effect of NaBr. The presence of 2 enlarged the range of temperature in which a 5 mM CTAB suspension in water + 50 mM NaBr clarifies. The initial micellization step which probably leads to micelles of 2 nearly fully neutralized by CTA⁺ ions was detected by spectrofluorometry with pyrene as fluorescent probe and took place at a CTAB concentration, C, below 0.1 mM. In both water and water + 50 mM NaBr, the electrical conductivity method was not sensitive to this micellization step. However, it detected a cmc at a much higher value of C which closely corresponds to a free CTA⁺ concentration equal to the cmc of CTAB alone. This second cmc is not detected by spectrofluorometry. The aggregation numbers of the mixed micelles are larger than those of CTAB micelles even at X as low as 0.02. At X = 0.091, the apparent aggregation number is very large, with a lower bound value of 410. Electron microscopy shows in this system the presence of vesicles and of very large aggregates, revealing that the system is close to precipitation under the experimental conditions used. Overall the results do not support the existence of the “cross-linked” micelles postulated to explain the large decrease of the NMR relaxation time T2 taking place upon addition of another anionic dimeric surfactant to the same CTAB system (Menger and Eliseev, Langmuir 1995, 11, 1855).