Bo Nyström

In this work, the diblock copolymer methoxy-poly(ethyleneglycol)-block-poly(epsilon-caprolactone) (MPEG-b-PCL) was synthesized with a block composition that allowsthis polymerin aqueous media to possess both an upper critical solution temperature(UCST) and a lower critical solution temperature (LCST) over a limitedtemperature interval. The value of the UCST, associated with crystallizationof the PCL-block, depended on heating (H) or cooling (C) of the sampleand was found to be CPUCST (H) = 32 C-circle andCP(UCST) (c) = 23 & DEG;C, respectively. The LCSTwas not affected by the heating or cooling scans; assumed a valueof C-circle (CPLCST (H) = CPLCST (c)). At intermediate temperatures (e.g., 45 C-circle), dynamiclight scattering (DLS), small-angle X-ray scattering (SAXS), and cryogenictransmission electron microscopy (cryo-TEM) showed that the solutionconsisted of a large population of spherical core-shell particlesand some self-assembled rodlike objects. At low temperatures (below32 C-circle), differential scanning calorimetry (DSC) and wide-angleX-ray scattering (WAXS) in combination with SAXS disclosed the formationof crystals with a cylindrical core-shell structure. Cryo-TEMsupported a thread-like appearance of the self-assembled polymer chains.At temperatures above 52 C-circle, incipient phase separation tookplace and large aggregation complexes of amorphous morphology wereformed. This work provides insight into the intricate interplay betweenUCST and LCST and the type of structures formed at these conditionsin aqueous solutions of MPEG-b-PCL diblockcopolymers.

It is known that the reduction of blood cholesterol can be accomplished through foods containing a large number of dietary fibers; this process is partially related to the binding of bile salt to fibers. To gain new insights into the interactions between dietary fibers and bile salts, this study investigates the interactions between cationic hydroxyethyl cellulose (catHEC) and sodium deoxycholate (NaDC) or sodium cholate (NaC), which have a similar structure. Turbidity measurements reveal strong interactions between catHEC and NaDC, and under some conditions, macroscopic phase separation occurs. In contrast, the interactions with NaC are weak. At a catHEC concentration of 2 wt %, incipient phase separation is approached at concentrations of NaC and NaDC of 32.5 and 19.3 mM, respectively. The rheological results show strong interactions and a prominent viscosification effect for the catHEC/NaDC system but only moderate interactions for the catHEC/NaC system. Both cryogenic transmission electron microscopy and small-angle X-ray scattering results display fundamental structural differences between the two systems, which may explain the stronger interactions in the presence of NaDC. The surmise is that the extended structures formed in the presence of NaDC can easily form connections and entanglements in the network.

Saponins are plant glycosides with different structures and biological activities, such as anticancer effects. Ziziphus spina-christi is a plant rich in saponin, and this compound is used to treat malignant melanoma in the present study. Nanophytosomes can be used as an advantageous nanodrug delivery system for plant extracts. The aim of this work is to use the saponin-rich fraction (SRF) from Z. spina-christi and prepare SRF-loaded nanophytosomes (saponinosomes) and observe the in vitro and in vivo effects of these carriers. First, the SRF was obtained from Z. spina-christi by a solvent-solvent fractionation method. Then, Fourier transform infrared (FTIR) analyses were performed to confirm the presence of saponins in the extracted material. Subsequently, the saponinosomes were prepared by the solvent injection method (ether injection method) using a 1:1:1 ratio of lecithin/cholesterol/SRF in the mixture. Characterization of the prepared saponinosomes was performed by FTIR, dynamic light scattering (DLS), field-emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM) analyses. In addition, a UV-vis spectrophotometer was used to determine the entrapment efficiency (EE) and in vitro release of the SRF. Finally, cell cytotoxicity of the different formulations was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay on both mouse melanoma cells (B16F10) and fibroblasts (L929). Using DLS, AFM, and FE-SEM analyses, the particle size was determined to be 58 ± 6 nm with a zeta potential of -32 ± 2 mV. The calculated EE was 85 ± 3%. The results of the in vitro release profile showed that 68.2% of the SRF was released from the saponinosome after 48 h. The results of the MTT assay showed that the SRF and saponinosomes have high toxicity on B16F10 melanoma cells, but saponinosomes showed a significant decrease in cytotoxicity on L929 fibroblast cells compared with that of the SRF. Our results indicate that the SRF from Z. spina-christi has anticancer activity, and the saponinosomes prepared in this work can control tumor growth, improve therapeutic efficacy, and reduce the side effects of saponins.

The rheological changes that occur during the chemical gelation of semidilute solutions of chitosan in the presence of the low-toxicity agent glyceraldehyde (GCA) are presented and discussed in detail. The entanglement concentration for chitosan solutions was found to be approximately 0.2 wt.% and the rheological experiments were carried out on 1 wt.% chitosan solutions with various amounts of GCA at different temperatures (25 °C and 40 °C) and pH values (4.8 and 5.8). High crosslinker concentration, as well as elevated temperature and pH close to the pK_a value (pH ≈ 6.3–7) of chitosan are three parameters that all accelerate the gelation process. These conditions also promote a faster solid-like response of the gel-network in the post-gel region after long curing times. The mesh size of the gel-network after a very long (18 h) curing time was found to contract with increasing level of crosslinker addition and elevated temperature. The gelation of chitosan in the presence of other chemical crosslinker agents (glutaraldehyde and genipin) is discussed and a comparison with GCA is made. Small angle neutron scattering (SANS) results reveal structural changes between chitosan solutions, incipient gels, and mature gels.

As a potent nonviral system for biomolecular delivery to neurons via their axons, we have studied molecular characteristics of lysinated fluorescent dextran nanoconjugates with degrees of conjugation of 0.54–15.2 mol lysine and 0.25–7.27 mol tetramethyl rhodamine isothiocyanate (TRITC) per mol dextran. We studied the influence of conjugation with lysine and TRITC on the size and structure of different molecular weight dextrans and their mobility within axons. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) experiments revealed significant differences in the size and structure of unmodified and modified dextrans. Unexpectedly, lower-molecular-weight conjugated dextrans exhibited higher molecular volumes, which we propose is due to fewer intramolecular interactions than in higher-molecular-weight conjugated dextrans. Assessment of retrograde and anterograde movement of lysine- and TRITC-conjugated dextrans in axons in the lumbar spinal cord of chicken embryos showed that lower-molecular-weight dextrans translocate more efficiently than higher-molecular-weight dextrans, despite having larger molecular volumes. This comparative characterization of different molecular weight dextrans will help define optimal features for intracellular delivery.

The self-assembly of two oppositely charged diblock copolymers that have a common thermosensitive nonionic block of poly(N-isopropylacrylamide) (pNIPAAM) has been investigated. The effect of the mixing ratio and total polymer concentrations on the self-assembly of the components and on the phase stability of the mixtures were studied by dynamic light scattering, electrophoretic mobility and turbidimetry measurements in water at 20 °C. The effect of the competing electrostatic and hydrophobic interactions on the nanostructure of negatively charged electrostatically self-assembled micelles bearing a pNIPAAM corona was investigated by small-angle X-ray scattering (SAXS). The electrostatic and hydrophobic interactions were controlled independently by tuning the ionic strength (from pure water to 50 mM NaCl) and the temperature (20 – 50 °C) of the investigated mixtures. The SAXS data could be fitted by a spherical micelle model, which has a smoothly decaying radial profile and a Gaussian star term that describes the internal structure of the micellar structures and possible attractive interactions between the polymer chains. At high temperature, a cluster structure factor was included for describing the formation of bulky clusters of the formed micelles. At low temperature and ionic strength, the formation of micelles with a coacervate core and hydrated pNIPAAM shell was observed. The structural evolution of the self-assembled micelles with increasing ionic strength and temperature could be followed and finally at high ionic strength and temperature the formation of inverted micelles with a hydrophobic core and polyelectrolyte shell could be identified.

The self‐assembly process in aqueous solutions of the methoxyl‐poly(ethylene glycol)‐block‐poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic sodium)‐block‐poly(N‐isopropyl acrylamide) (PNIPAAM) triblock copolymer, synthesized via two different atomic transfer radical polymerization methods, namely “one‐pot” (P3‐sample) and “two‐pot” (P2‐sample), was studied by various experimental techniques. The “one‐pot” procedure leads to a copolymer (P3) where the PNIPAAM block is contaminated with a minor quantity of 2‐acrylamido‐2‐methyl‐1‐propane sulfonate (AMPS) residuals and this sample does not form micelles over the considered temperature region, but unimers and temperature‐induced aggregates coexist in the presence of a small amount of salt. The P2 polymer forms micelles and intermicellar structures, but the former moieties disappear at high temperatures, whereas the latter species contract with increasing temperature. Small‐angle neutron scattering results revealed correlation peaks, both for P3 and P2, and no micelle formation for P3, but a pronounced upturn of the scattered intensity at low wavevector values at elevated temperatures for the P2 copolymer. The findings from this study clearly show that the spurious AMPS residuals have a drastic influence on the self‐assembly and micelle formation of the triblock copolymer. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 524–534