Nanocomposite gels of poloxamine and Laponite for ß-Lapachone release in anticancer therapy.

Nano-hybrid systems have been shown to be an attractive platform for drug delivery. Laponite® RD (LAP), a biocompatible synthetic clay, has been exploited for its ability to establish of strong secondary interactions with guest compounds and hybridization with polymers or small molecules that improves, for instance, cell adhesion, proliferation, and differentiation or facilitates drug attachment to their surfaces through charge interaction. In this work, LAP was combined with Tetronics, X-shaped amphiphilic PPO-PEO (poly (propylene oxide)-poly (ethylene oxide) block copolymers. ß-Lapachone (BLPC) was selected for its anticancer activity and its limited bioavailability due to very low aqueous solubility, with the aim to improve this by using LAP/Tetronic nano-hybrid systems. The nanocarriers were prepared over a range of Tetronic 1304 concentrations (1 to 20% w/w) and LAP (0 to 3% w/w). A combination of physicochemical methods was employed to characterize the hybrid systems, including rheology, particle size and shape (DLS, TEM), thermal analysis (TG and DSC), FTIR, solubility studies and drug release experiments. In vitro cytotoxicity assays were performed with BALB/3T3 and MCF-7 cell lines. In hybrid systems, a sol-gel transition can occur below physiological temperature. BLPC exhibits the most significant increase in solubility in formulations with a high concentration of T1304 (over 10% w/w) and 1.5% w/w LAP, or systems with only LAP (1.5%), with a 50 and 100-fold increase in solubilisation, respectively. TEM images showed spherical micelles of T1304, which elongated into wormlike micelles with concentration (20%) and in the presence of LAP, a finding that has not been reported before. A sustained release of BLPC over 140 hours was achieved in one of the formulations (10% T1304 with 1.5% laponite), which also showed the best selectivity index towards cancer cells (MCF-7) over BALB/3T3 cell lines. In conclusion, BLPC-loaded T1304/LAP nano-hybrid systems proved safe and highly effective and are thus a promising formulation for anticancer therapy.

Tuning the viscoelastic properties of bis(urea)-based supramolecular polymer solutions by adding cosolutes.

Polymers formed by the self-assembly of a bis(urea)-based polymer, 2,4-bis(2-ethylhexylureido)toluene (EHUT), in organic solvents such as octane are promising systems with remarkable rheological properties. This is the first self-assembled polymer recently reported as a hydrodynamic drag reducer for hydrocarbons. The rheology of diluted and semidiluted EHUT solutions can be tuned by specific interactions between the chains, modulated by the nature of the solvent and the presence of additives. In this article, rheological, thermal and SANS measurements were performed in order to investigate the competition between EHUT self-assembly and its interaction with specific molecules (benzene, benzyl alcohol, and ethanol) that can interact with EHUT unimers via hydrogen bonds and π-π interactions. No substantial rheological, thermal, or structural effect is observed when benzene is added to the systems. However, ethanol and benzyl alcohol interact with EHUT unimers through hydrogen bonds, drastically decreasing the viscoelasticity of the solutions. In addition, benzyl alcohol can interact with EHUT polymers by π-stacking interactions, playing an important role in tuning the rheological properties of the systems.

Retinyl palmitate polymeric nanocapsules as carriers of bioactives.

Nanocapsules containing poly(d,l-lactide) shell and retinyl palmitate core have been prepared by the pre-formed polymer interfacial deposition method. Dynamic light scattering measurements yielded an average hydrodynamic diameter of ∼220nm and a polydispersity index of ∼0.12. Small-angle neutron scattering experiments revealed the presence of two populations of nanocapsules of core diameters ∼192 and 65nm. Freeze fracture transmission electron microscopy showed a polydisperse population of nanocapsules (NC), with a poly(d,l-lactide) shell thickness between 11 and 3nm. For comparison purposes, nanoemulsions (NE, no polymer) and nanospheres (NS, polymer matrix) were also prepared. Each type of nanoparticles exhibited a different morphology (when examined by electron microscopy), in particular NC showed deformability by capillary adhesion. All three types of nanoparticles successfully encapsulated the poorly water-soluble molecules baicalein and benzophenone-3. The thermal behavior of the various nanoparticles was different to a physical mixture of its individual components. Cytotoxicity and phototoxicity assays, performed in human keratinocytes (HaCaT) and murine fibroblasts (BALB/c 3T3), showed that the NC were only cytotoxic at high concentrations. In vitro release studies of benzophenone-3, by the dialysis bag method using NC and NS, showed a sustained release; however, permeation studies using plastic surgery human abdominal skin in Franz diffusion cells showed that a higher amount of benzophenone-3 from NC penetrated into the skin, most probably due to the deformable nature of these nanoparticles.

Wormlike micellar aggregates of saponins from Ilex paraguariensis A. St. Hil. (mate): a characterisation by cryo-TEM, rheology, light scattering and small-angle neutron scattering.

This work reports the physico-chemical characterisation of the micellar structures formed by a saponin fraction obtained from an important South American species, Ilex paraguariensis (mate). The mate saponin-enriched fraction (MSF) mainly comprises triterpenic glycosides and was obtained from mate green fruits through solid-phase extraction. The physico-chemical studies focused on the determination of the critical micellar concentration (CMC), the size and shape of the micelles, using conventional transmission electronic microscopy (TEM), as well as Cryo-TEM, light scattering and small-angle neutron scattering. The rheological behaviour of the solutions up to 4 wt% was also determined using a controlled-strain rheometer. Finally, the MSF ability to solubilise poorly water-soluble drugs was assayed using carbamazepine and flurbiprofen as basic and weak acidic drug models. Small spherical micelles of around 20 Å radius were observed in the presence of elongated structures with lengths of more than 500 nm, possessing a well-defined CMC of 0.41 g/L. MSF solutions ranging from 0.25 to 4% (w/v) demonstrated a viscoelastic behaviour independent of the concentration. MSF could improve the solubility of carbamazepine in the range of 0.13 to 1.5% (w/v).

Effect of monomeric and polymeric co-solutes on cetyltrimethylammonium bromide wormlike micelles: rheology, Cryo-TEM and small-angle neutron scattering.

The effect of hydrophobic and hydrophilic co-solutes on the rheological properties of wormlike micelles of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal) or sodium bromide (NaBr) was investigated. Monomeric (ethanol, 2-propanol, benzene and benzylic alcohol) and polymeric species (poly(ethylene oxide), poly(vinyl alcohol) and poly(propylene oxide), respectively PEO, PVA and PPO) of varying molecular weight were studied in order to assess the effect of co-solute 'length' on the interactions with the wormlike micelles. Rheological properties were characterised by the plateau modulus G(0) and the relaxation time τ(R) obtained from fits to the Maxwell model, and by the zero-shear viscosity η(0). The rheological properties were unaltered by the addition of all hydrophilic solutes (up to 20 mM). With hydrophobic co-solutes instead, both η(0) and τ(R) decreased considerably, while G(0) was unaffected. The effects were particularly remarkable with PPO for concentrations as low as 5 mM (ca. 0.3 g L(-1)), and τ(R) was seen to follow an exponential decrease with polymer M(w). The effect of the aromatic solutes (benzene and benzyl alcohol) on the rheology was highly dependent on the counterions used to induce micellar growth (Sal(-) or Br(-)), revealing a different type of interaction. Surprisingly, small-angle neutron scattering and Cryo-TEM measurements showed that the drastic changes observed in the rheology were not correlated to any visible structural change. Therefore the strong decrease in viscosity and relaxation time are to be attributed to other mechanisms than micellar break-up or rod-to-sphere transition.