Self-Assembly of Soluplus in Aqueous Solutions: Characterization and Prospectives on Perfume Encapsulation.

Soluplus is an amphiphilic graft copolymer intensively studied as a micellar solubilizer for drugs. An extensive characterization of the nanostructure of its colloidal aggregates is still lacking. Here, we provide insights into the polymer's self-assembly in water, and we assess its use as an encapsulating agent for fragrances. The self-assembly properties of Soluplus aqueous solutions were studied over a wide concentration range (1-70% w/w) by means of small-angle neutron scattering (SANS), differential scanning calorimetry, NMR, and rheometry. SANS analyses revealed the presence of polymeric micelles with a fuzzy surface interacting via a 2-Yukawa potential, up to 15% w/w polymer. Increasing the polymer concentration up to 55% w/w led to tightly packed micelles described according to the Teubner-Strey model. The ability of Soluplus to encapsulate seven perfume molecules, 2-phenyl ethanol, l-carvone, linalool, florhydral, ß-citronellol, α-pinene, and R-limonene, was then examined. We showed that the fragrance's octanol/water partition coefficient (log Kow), widely used to characterize the solubilization capacity, is not sufficient to characterize such systems and the presence of specific functional groups or molecular conformation needs to be considered. In fact, the combination of SANS, NMR, confocal laser scanning microscopy, and confocal Raman microscopy showed that the perfumes, interacting with different regions of the polymer aggregates, are able to tune the systems' structures resulting in micelles, matrix-type capsules, core-shell capsules, or oil-in-water emulsions.

Encapsulation of volatile compounds in liquid media: Fragrances, flavors, and essential oils in commercial formulations.

The first marketed example of the application of microcapsules dates back to 1957. Since then, microencapsulation techniques and knowledge have progressed in a plethora of technological fields, and efforts have been directed toward the design of progressively more efficient carriers. The protection of payloads from the exposure to unfavorable environments indeed grants enhanced efficacy, safety, and stability of encapsulated species while allowing for a fine tuning of their release profile and longer lasting beneficial effects. Perfumes or, more generally, active-loaded microcapsules are nowadays present in a very large number of consumer products. Commercial products currently make use of rigid, stable polymer-based microcapsules with excellent release properties. However, this type of microcapsules does not meet certain sustainability requirements such as biocompatibility and biodegradability: the leaking via wastewater contributes to the alarming phenomenon of microplastic pollution with about 4% of total microplastic in the environment. Therefore, there is a need to address new issues which have been emerging in relation to the poor environmental profile of such materials. The progresses in some of the main application fields of microencapsulation, such as household care, toiletries, cosmetics, food, and pesticides are reviewed herein. The main technologies employed in microcapsules production and the mechanisms underlying the release of actives are also discussed. Both the advantages and disadvantages of every technique have been considered to allow a careful choice of the most suitable technique for a specific target application and prepare the ground for novel ideas and approaches for encapsulation strategies that we expect to be proposed within the next years.

Rational Design of Sustainable Liquid Microcapsules for Spontaneous Fragrance Encapsulation.

The high volatility, water-immiscibility, and light/oxygen-sensitivity of most aroma compounds represent a challenge to their incorporation in liquid consumer products. Current encapsulation methods entail the use of petroleum-based materials, initiators, and crosslinkers as well as mixing, heating, and purification steps. Hence, more efficient and eco-friendly approaches to encapsulation must be sought. Herein, we propose a simple method by making use of a pre-formed amphiphilic polymer and employing the Hansen Solubility Parameters approach to determine which fragrances could be encapsulated by spontaneous coacervation in water. The coacervates do not precipitate as solids but they remain suspended as colloidally stable liquid microcapsules, as demonstrated by fluorescence correlation spectroscopy. The effective encapsulation of fragrance is proven through confocal Raman spectroscopy, while the structure of the capsules is investigated by means of cryo FIB/SEM, confocal laser scanning microscopy, and small-angle X-ray scattering.

Tuning the Encapsulation of Simple Fragrances with an Amphiphilic Graft Copolymer.

The encapsulation of poorly water-soluble compounds such as perfumes, flavors, and bioactive molecules is a key step in the formulation of a large variety of consumer products in the fields of household care and personal care. We study the encapsulation ability of an amphiphilic poly(ethylene glycol)-graft-poly(vinyl acetate) (PEG-g-PVAc) graft copolymer, extending the focus to the entire phase diagram of polymer/perfume/water systems with three common natural fragrances. The three perfume molecules (2-phenyl ethanol, L-carvone, and α-pinene) possess different water affinities, as expressed by their octanol/water partition coefficients. The investigation of the polymorphism of PEG-g-PVAc in these systems is carried out by means of dynamic light scattering, small-angle X-ray scattering, NMR spectroscopy, and confocal laser scanning microscopy. The results presented here demonstrate that the choice of fragrance can dramatically affect the supramolecular structures formed by the polymer in aqueous solution, with important consequences on formulations of industrial interest such as the demixing of complex perfume blends when one or more of the components have no chemical affinity for any of the polymer blocks.

Multifunctional cubic liquid crystalline nanoparticles for chemo- and photodynamic synergistic cancer therapy.

With the aim of engineering multifunctional nanoparticles useful for cancer therapy, a diketopyrrolopyrrole-porphyrin based photosensitizer was here conjugated to a block copolymer (Pluronic F108), and used to stabilize in water lipidic cubic liquid crystalline nanoparticles (cubosomes), also loaded with the antineoplastic agent docetaxel. The physicochemical characterization by SAXS, DLS, and cryo-TEM demonstrated that the formulation consisted of cubosomes, about 150 nm in size, possessing a bicontinuous cubic structure (space group Pn3m). The cellular imaging experiments proved that these nanoparticles localized in lysosomes and mitochondria, while cytotoxicity tests evidenced a slight but significant synergistic effect which, after irradiation, increased the toxicity induced by docetaxel alone, allowing further reduction of cell viability.

Associative properties of poly(ethylene glycol)-poly(vinyl acetate) comb-like graft copolymers in water.

The self-assembly of amphiphilic graft copolymers is generally reported for polymer melts or polymers deposited onto surfaces, while a small number of cases deal with binary mixtures with water. We report on the associative properties of poly(ethylene glycol)-graft-poly(vinyl acetate) (PEG-g-PVAc) comb-like copolymers in water, demonstrating the existence of a percolative behaviour when increasing the PEG-g-PVAc content. Rheology, light- and small-angle X-ray scattering experiments, together with dissipative particle dynamics simulations, reveal a progressive transition from spherical polymer single-chain nanoparticles (SCNPs) towards hierarchically complex structures as the weight fraction of the polymer in water increases. The ability of PEG-g-PVAc to attain different nano- and microstructures is of great importance in numerous applications such as in the fields of cosmetics, detergency and drug delivery.

A small heterobifunctional ligand provides stable and water dispersible core-shell CdSe/ZnS quantum dots (QDs).

We describe a simple method to prepare water dispersible core-shell CdSe/ZnS quantum dots (QDs) 1 by capping QDs with a new thiol-containing heterobifunctional dicarboxylic ligand 4 (DHLA-EDADA). This ligand, obtained on a gram scale through a few synthetic steps, provides a compact layer on the QDs, whose hydrodynamic size in H2O is 15 nm ± 3 nm. The colloidal stability is dramatically enhanced with respect to the well-known (±) α-lipoic acid (DHLA). The ligand affinity towards QDs and the water dispersibility of nanocrystals 1 are addressed by the dithiol groups of DHLA, which chelate the zinc of the shell, and by the dicarboxylic groups of the ethylenediamine-N,N-diacetic acid (EDADA) residue, respectively. The effects of pH, buffer solutions, and biological medium on the stability of QDs 1 were assessed by monitoring the photoluminescence (PL) and hydrodynamic size over time. Highly fluorescent QD dispersions, stable over extended periods of time and over broad pH ranges and buffer types, were obtained. Furthermore, we show that the DHLA-EDADA ligand 4 also endows QDs with functional groups suitable for further conjugation and for metal ion detection. As a case study to illustrate the potential of our approach, we report the preparation and characterization of a highly luminescent orange light emitting polymer-QD 1 composite film.

Nonaqueous Microemulsion in the Bmim Tf2N/Brij 30/ n-Nonane System: Structural Investigation and Application as Gold Nanoparticle Microreactor.

Microemulsions based on ionic liquids (ILs) are being increasingly studied in many different areas of physical chemistry because of the attractive properties of ILs. In particular, waterless microemulsions where the IL represents the polar phase can be of interest for those applications that demand the nanosegregation of polar substances, but in which the absence of water is a strict requirement. In this work, we prepared a reverse, nonaqueous microemulsion based on the low-viscosity room-temperature IL, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide , the surfactant Brij 30, and n-nonane. The systems were characterized by dynamic light scattering and small-angle X-ray scattering; the IL/oil microemulsion was further employed as a templating system for the synthesis of gold nanoparticles from hydrogen tetrachloroaurate(III), HAuCl4, by UV-photoreduction technique.

Inclusion of oligonucleotide antimicrobials in biocompatible cationic liposomes: A structural study.

HYPOTHESIS: Transcription factor decoys (TFD) are short oligonucleotides designed to block essential genetic pathways in bacteria and defeat resistant infections. TFD protection in biological fluids and their delivery to the site of infection require formulation in appropriate delivery systems. In this work, we build on a classical phosphatidylcholine/phosphatidylethanolamine (POPC/DOPE) scaffold to design TFD-loaded cationic liposomes by combining the DNA-complexing abilities of a bolaamphiphile, (1,1'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), with the biocompatible cationic lipid ethyl-phosphatidylcholine (DPePC). The goal is to perform a structural study to determine the impact of the bolaamphiphile and TFD incorporation on the liposome structure, the capacity for TFD encapsulation, and the colloidal stability in saline media and cell culture environments. EXPERIMENTS: The systems are characterized by means of dynamic light scattering, small-angle X-ray scattering, and ζ-potential measurements, to provide a clear picture of the liposome structure. Circular dichroism (CD) spectroscopy is used to assess the compaction of the oligonucleotide in a psi form, while steady-state fluorescence and fluorescence correlation spectroscopies give insight into the entrapment rate and distribution of the TFD in the liposomes. FINDINGS: We found that the combination of the two cationic species, 12-bis-THA and DPePC, allows encapsulation of 90% of the TFD. Results of CD experiments revealed that the TFD is condensed, therefore likely protected from the lytic action of serum nucleases. Finally, the systems showed colloidal stability in aqueous dispersion with ionic strength comparable to biologically relevant media.

Cationic liposomal vectors incorporating a bolaamphiphile for oligonucleotide antimicrobials.

Antibacterial resistance has become a serious crisis for world health over the last few decades, so that new therapeutic approaches are strongly needed to face the threat of resistant infections. Transcription factor decoys (TFD) are a promising new class of antimicrobial oligonucleotides with proven in vivo activity when combined with a bolaamphiphilic cationic molecule, 12-bis-THA. These two molecular species form stable nanoplexes which, however, present very scarce colloidal stability in physiological media, which poses the challenge of drug formulation and delivery. In this work, we reformulated the 12-bis-THA/TFD nanoplexes in a liposomal carrier, which retains the ability to protect the oligonucleotide therapeutic from degradation and deliver it across the bacterial cell wall. We performed a physical-chemical study to investigate how the incorporation of 12-bis-THA and TFD affects the structure of POPC- and POPC/DOPE liposomes. Analysis was performed using dynamic light scattering (DLS), ζ-potential measurements, small-angle x-ray scattering (SAXS), and steady-state fluorescence spectroscopy to better understand the structure of the liposomal formulations containing the 12-bis-THA/TFD complexes. Oligonucleotide delivery to model Escherichia coli bacteria was assessed by means of confocal scanning laser microscopy (CLSM), evidencing the requirement of a fusogenic helper lipid for transfection. Preliminary biological assessments suggested the necessity of further development by modulation of 12-bis-THA concentration in order to optimize its therapeutic index, i.e. the ratio of antibacterial activity to the observed cytotoxicity. In summary, POPC/DOPE/12-bis-THA liposomes appear as promising formulations for TFD delivery.

Synthesis and binding monitoring of a new nanomolar PAMAM-based matrix metalloproteinases inhibitor (MMPIs).

Dendrimers are efficient drug delivery systems particularly useful in ocular diseases. In particular, low generation PAMAM dendrimers are non-toxic and non-immunogenic and they provide an enhancement of the residence time of drugs in the eyes. In this context, the synthesis of the PAMAM-based matrix metalloproteinases inhibitor 5, is reported. In particular, we demonstrated that 5 strongly binds (18.0nM±2.5nM) MMP-9, the most relevant MMP responsible of ocular surface damages in induced dry eyes syndrome (DES).

Interaction between a cationic bolaamphiphile and DNA: The route towards nanovectors for oligonucleotide antimicrobials.

Bacterial resistance to antimicrobials is a global threat that requires development of innovative therapeutics that circumvent its onset. The use of Transcription Factor Decoys (TFDs), DNA fragments that act by blocking essential transcription factors in microbes, represents a very promising approach. TFDs require appropriate carriers to protect them from degradation in biological fluids and transfect them through the bacterial cell wall into the cytoplasm, their site of action. Here we report on a bolaform cationic surfactant, [12-bis-THA]Cl2, with proven transfection activity in vivo. By studying the physical-chemical properties of its aqueous solutions with light scattering, cryo-TEM, ζ-potential, absorption and fluorescence spectroscopies, we prove that the bolaamphiphiles associate into transient vesicles which convert into one-dimensional elongated structures over time. These surfactant assemblies complex TFDs with extremely high efficiency, if compared to common cationic amphiphiles. At Z+/-=11, the nanoplexes are stable and have a size of 120nm, and they form independently of the original morphology of the [12-bis-THA]Cl2 aggregate. DNA is compacted in the nanoplexes, as shown through CD spectroscopy and fluorescence, but is readily released in its native form if sodium taurocholate is added.

Concentrated assemblies of magnetic nanoparticles in ionic liquids.

Maghemite (γ-Fe2O3) nanoparticles (NPs) can be successfully dispersed in a protic ionic liquid, ethylammonium nitrate (EAN), by transfer from aqueous dispersions into EAN. As the aqueous systems are well controlled, several parameters can be tuned. Their crucial role towards the interparticle potential and the structure of the dispersions is evidenced: (i) the size of the NPs tunes the interparticle attraction monitoring dispersions to be either monophasic or gas-liquid-like phase separated; (ii) the nature of the initial counterion in water (here sodium, lithium or ethylammonium) and the amount of added water (<20 vol%) modulate the interparticle repulsion. Very concentrated dispersions with a volume fraction of around 25% are obtained thanks to the gas-liquid-like phase separations. Such conclusions are derived from a fine structural and dynamical study of the dispersions on a large range of spatial scales by coupling several techniques: chemical analyses, optical microscopy, dynamic light scattering, magneto-optic birefringence and small angle scattering.

Aerosol-OT in water forms fully-branched cylindrical direct micelles in the presence of the ionic liquid 1-butyl-3-methylimidazolium bromide.

A recent investigation on the sodium bis(2-ethylhexyl)sulfosuccinate/water/1-butyl-3-methylimidazolium tetrafluoborate (NaAOT/W/bmimBF(4)) system showed that the anionic two-tailed surfactant NaAOT, that is known to form reverse micelles or planar interfaces (typically lamellar liquid crystals), can originate discrete spherical micelles of normal curvature because of strong interactions with the ionic liquid. The goal of the present paper was to detect macro- and microscopic modifications within such a system upon substitution of the ionic liquid's counter-ion tetrafluoroborate with bromide. Firstly, the phase diagram of the NaAOT/water/bmimBr system was determined. Then, the monophasic regions were investigated by means of NMR self-diffusion and SAXRD experiments. The results obtained proved this system to be surprisingly different from that containing bmimBF(4). This study focused mainly on the characterization of the micellar region, which turned out to be constituted of a bicontinuous nanostructure. This finding can be accounted for suggesting a decreasing of the NaAOT effective surfactant packing parameter, as in the case of NaAOT/water/bmimBF(4) system, although the effect in the presence of Br(-) is less pronounced. Data modeling showed the same degree of interfacial adsorption for the bmim(+) cation in both systems, regardless of the particular counterion used-either BF(4)(-) or Br(-). Thus, the remarkable differences between the two systems appear to be mainly due to a specific counterion effect. This result highlights once again the ions specificity, which is found ubiquitously in chemistry and biology.

Aerosol-OT forms oil-in-water spherical micelles in the presence of the ionic liquid bmimBF4.

The phase diagram sodium bis(2-ethylhexyl) sulfosuccinate (NaAOT)/water/1-butyl-3-methylimidazolium tetrafluoborate (bmimBF(4)), a polar room temperature ionic liquid, is explored through optical microscopy in polarized light, SAXRD and NMR PGSTE techniques. The analysis of SAXRD and self-diffusion data reveals that the bmim(+) cation is strongly adsorbed at the interface. Data are accounted for by Hill's model for cooperative binding. The overall process is described as a comicellization of AOT(-) and bmim(+) involving roughly two cations for AOT(-) ion. The bmim(+) is severely involved in the structural arrangement of the interface. Indeed, a huge modification of the interfacial geometry resulting in the occurrence of micelles having positive curvature is inferred from the analysis of the self-diffusion coefficients. The analysis of the water diffusion data in the L(1) phase (according to the effective cell model) allows one to exclude the presence of oblate and/or discoid micelles. Finally, the study of the oil diffusion in samples doped with p-xylene permits one to assess furthermore not only the formation of AOT aggregates of the oil-in-water type but also the occurrence of dynamic percolation phenomena.