Angiopep-2-Functionalized Lipid Cubosomes for Blood-Brain Barrier Crossing and Glioblastoma Treatment.

Glioblastoma multiforme (GBM) is an aggressive brain cancer with high malignancy and resistance to conventional treatments, resulting in a bleak prognosis. Nanoparticles offer a way to cross the blood-brain barrier (BBB) and deliver precise therapies to tumor sites with reduced side effects. In this study, we developed angiopep-2 (Ang2)-functionalized lipid cubosomes loaded with cisplatin (CDDP) and temozolomide (TMZ) for crossing the BBB and providing targeted glioblastoma therapy. Developed lipid cubosomes showed a particle size of around 300 nm and possessed an internal ordered inverse primitive cubic phase, a high conjugation efficiency of Ang2 to the particle surface, and an encapsulation efficiency of more than 70% of CDDP and TMZ. In vitro models, including BBB hCMEC/D3 cell tight monolayer, 3D BBB cell spheroid, and microfluidic BBB/GBM-on-a-chip models with cocultured BBB and glioblastoma cells, were employed to study the efficiency of the developed cubosomes to cross the BBB and showed that Ang2-functionalized cubosomes can penetrate the BBB more effectively. Furthermore, Ang2-functionalized cubosomes showed significantly higher uptake by U87 glioblastoma cells, with a 3-fold increase observed in the BBB/GBM-on-a-chip model as compared to that of the bare cubosomes. Additionally, the in vivo biodistribution showed that Ang2 modification could significantly enhance the brain accumulation of cubosomes in comparison to that of non-functionalized particles. Moreover, CDDP-loaded Ang2-functionalized cubosomes presented an enhanced toxic effect on U87 spheroids. These findings suggest that the developed Ang2-cubosomes are prospective for improved BBB crossing and enhanced delivery of therapeutics to glioblastoma and are worth pursuing further as a potential application of nanomedicine for GBM treatment.

Fatty acid/monoglyceride type and amount modulate fat-soluble vitamin absorption from mixed assemblies in mice.

We investigated the effects of fatty acid/ monoglyceride type and amount on the absorption of fat-soluble vitamins. Micelles or vesicles made with either caprylic acid (CA) + monocaprylin (MC) or oleic acid (OA) + monoolein (MO) at low or high concentrations were infused in bile duct-ligated mice. Retinol + retinyl ester and γ-tocopherol intestinal mucosa contents were higher in mice infused with CA + MC than with OA + MO (up to + 350 % for vitamin A and up to + 62 %, for vitamin E; p < 0.05). Cholecalciferol intestinal mucosa content was the highest in mice infused with micelles with CA + MC at 5 mg/mL (up to + 105 %, p < 0.05). Retinyl ester plasma response was higher with mixed assemblies formed at low concentration of FA + MG compared to high concentration (up to + 1212 %, p < 0.05), while no difference in cholecalciferol and γ-tocopherol plasma responses were measured. No correlation between size or zeta potential and vitamin absorption was found. The impact of FA and MG on fat-soluble vitamin absorption thus differs from one vitamin to another and should be considered to formulate adequate vitamin oral or enteral supplements.

Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro.

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.

Antimicrobial and antibiofilm effects of shikonin with tea tree oil nanoemulsion against Candida albicans and Staphylococcus aureus.

The current work aims to develop a shikonin and tea tree oil loaded nanoemulsion system stabilized by a mixture of GRAS grade surfactants (Tween 20 and monoolein) and a cosurfactant (Transcutol P). This system was designed to address the poor aqueous solubility and photostability issues of shikonin. The authenticity of shikonin employed in this study was confirmed using nuclear magnetic resonance (NMR) spectroscopy. The optimized nanoemulsion exhibited highly favorable characteristics in terms of zeta potential (-23.8 mV), polydispersity index (0.216) and particle size (22.97 nm). These findings were corroborated by transmission electron microscopy (TEM) micrographs which confirmed the spherical and uniform nature of the nanoemulsion globules. Moreover, attenuated total reflectance (ATR) and X-ray diffraction analysis (XRD) analysis affirmed improved chemical stability and amorphization, respectively. Photodegradation studies were performed by exposing pure shikonin and the developed nanoemulsion to ultraviolet light for 1 h using a UV lamp, followed by high performance liquid chromatography (HPLC) analysis. The results confirmed that the developed nanoemulsion system imparts photoprotection to pure shikonin in the encapsulated system. Furthermore, the research investigated the effect of the nanoemulsion on biofilms formed by Candida albicans and methicillin resistant Staphylococcus aureus (MRSA). Scanning electron microscopy, florescence microscopy and phase contrast microscopy unveiled a remarkable reduction in biofilm area, accompanied by disruptions in the cell wall and abnormalities on the cell surface of the tested microorganisms. In conclusion, the nanoencapsulation of shikonin with tea tree oil as the lipid phase showcased significantly enhanced antimicrobial and antibiofilm potential compared to pure shikonin against resistant strains of Candida albicans and Staphylococcus aureus.

A short review on the applicability and use of cubosomes as nanocarriers.

Abstract: Cubosomes are nanostructured lipid-based particles that have gained significant attention in the field of drug delivery and nanomedicine. These unique structures consist of a three-dimensional cubic lattice formed by the self-assembly of lipid molecules. The lipids used to construct cubosomes are typically nonionic surfactants, such as monoolein, which possess both hydrophilic and hydrophobic regions, allowing them to form stable, water-dispersible nanoparticles. One of the key advantages of cubosomes is their ability to encapsulate and deliver hydrophobic as well as hydrophilic drugs. The hydrophobic regions of the lipid bilayers provide an ideal environment for incorporating lipophilic drugs, while the hydrophilic regions can encapsulate water-soluble drugs. This versatility makes cubosomes suitable for delivering a wide range of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids. The unique structure of cubosomes also offers stability and controlled release benefits. The lipid bilayers provide a protective barrier, shielding the encapsulated drugs from degradation and improving their stability. Moreover, the cubic lattice arrangement enables the modulation of drug release kinetics by varying the lipid composition and surface modifications. This allows for the development of sustained or triggered drug release systems, enhancing therapeutic efficacy and reducing side effects. Furthermore, cubosomes can be easily modified with targeting ligands or surface modifications to achieve site-specific drug delivery, enhancing therapeutic selectivity and reducing off-target effects. In conclusion, cubosomes offer a versatile and promising platform for the delivery of therapeutic agents. In this manuscript, we will highlight some of these applications.

Lipid-Based Nanosystems for the Topical Application of Ferulic Acid: A Comparative Study.

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.

Cubosome Lipid Nanocarriers As a Drug Delivery Vehicle for Intracellular Mycobacterium tuberculosis Infections.

Mycobacterium tuberculosis (MTB) causes the infectious disease tuberculosis (TB), responsible for more deaths than any other single infectious disease in history. Intracellular MTB are slow growing and difficult to target with traditional antitubercular drugs, leading to the emergence of multidrug resistance in TB infection, which is a major global public health issue. Recent advances in innovative lipid nanotechnologies for drug delivery have demonstrated promising outcomes for chronic infectious diseases but have not yet been tested as potential delivery systems for intracellular infections such as TB. The current study evaluates the potential of monoolein (MO)-based cationic cubosomes for the encapsulation and delivery of the first line antitubercular drug rifampicin (RIF) against an MTB-H37Ra in vitro culture model. In particular, we show that the use of cationic cubosomes as delivery vehicles reduced the minimum inhibitory concentration (MIC) of RIF by 2-fold against actively replicating MTB-H37Ra (compared to that of the free drug) and also shortened the lifecycle duration of axenic MTB-H37Ra from 5 to 3 days. The cubosome-mediated delivery was also found to be effective against intracellular MTB-H37Ra within THP-1 human macrophages, with a 2.8 log reduction in viability of the bacilli after 6 days incubation at the MIC. The killing time was also reduced from 8 to 6 days without distressing the host macrophages. Mechanistic studies on the uptake of RIF-loaded cationic cubosomes using total internal reflection fluorescence microscopy (TIRFM) demonstrated the capacity of these lipid particles to effectively target intracellular bacteria. Overall, these results demonstrate that cationic cubosomes are a potent delivery system for the antitubercular drug RIF for therapeutic management of TB.

A novel droplet-based approach to study phase transformations in lyotropic liquid crystalline systems.

HYPOTHESIS: Lyotropic liquid crystals (LLC) and their phase transformations in response to stimuli have gathered much interest for controlled and 'on-demand' drug applications. Bulk methods of preparation impose limitations on studying the transformations, especially induced by compositional changes, such as enzymatic changes to lipid structure. Here we hypothesise that controlled microfluidic production and coalescence of dissimilar aqueous and lipid droplets emulsified in a third mutually immiscible liquid will provide a new approach to the spatio-temporal study of structure formation in lyotropic liquid crystalline materials. EXPERIMENTS: Separate lipid and aqueous droplets, dispersed in a fluorocarbon oil were generated using a microfluidic format. The chip, prepared as a hybrid polydimethylsiloxane (PDMS) and glass microfluidic device, was constructed to enable in-situ acquisition of time-resolved synchrotron small angle X-ray scattering (SAXS) and crossed polarised light microscopy of the coalesced droplets to determine the structures present during aging. FINDINGS: Janus-like droplets formed upon coalesce, with distinct lipid and aqueous portions with a gradient between the two sides of the merged droplet. SAXS and polarised light microscopy revealed a progression of mesophases as the lipid portion was hydrated by the aqueous portion via the diffusion limited interface which separated the portions. Thus demonstrating, on a droplet scale, a new approach for studying the phase transformation kinetics and identification of non-equilibrium phase in droplet-based lyotropic liquid systems.

Monoolein-based nanodispersions for cutaneous co-delivery of methylene blue and metformin: Thermal and structural characterization and effects on the cutaneous barrier, skin penetration and cytotoxicity.

This study evaluated the potential of monoolein (MO)-based nanodispersions to promote the cutaneous co-delivery of metformin (MET) and methylene blue (MB) for the treatment of non-melanoma skin cancer. MO-based nanodispersions were obtained using Kolliphor® P407 (KP) and/or sodium cholate (CH), and characterized concerning the structure, thermal stability, ability to disrupt the skin barrier, cutaneous permeation and retention of MB and MET. Additionally, the cytotoxic effect of MO nanodispersions-mediated combination therapy using MET and MB in A431 cells was evaluated. The nanodispersions exhibited nanometric size (<200 nm) and thermal and physical stability. Small angle X-ray scattering studies revealed multiple structures depending on composition. They were able to interact with stratum corneum lipid structure, increasing its fluidity. The effect of MO-nanodispersions on topical/transdermal delivery of MB and MET was composition-dependent. Nanodispersions with low MO content (5 %) and stabilized with KP and CH (0.05-0.10 %) were the most promising, enhancing the cutaneous delivery of MB and MET by 1.9 to 2.2-fold and 1.4 to 1.7-fold, respectively, compared to control. Cytotoxic studies revealed that the most promising MO nanodispersion-mediated combination therapy using MET and MB (1:1) reduced the IC50 by 24-fold, compared to MB solution, and a further reduction (1.5-fold) was observed by MB photoactivation.

Formation of particulate lipid lyotropic liquid crystalline nanocarriers using a microfluidic platform.

HYPOTHESIS: Non-lamellar lyotropic liquid crystal nanoparticles (LLCNPs) are gaining significant interest in the fields of drug delivery and nanomedicine. Traditional, top-down formulation strategies for LLCNPs are typically low-throughput, can lack controllability and reproducibility in the particle size distribution, and may be unsuitable for loading more fragile therapeutics. The development of a controllable, reproducible, scalable, and high-throughput strategy is urgently needed. EXPERIMENTS: Monoolein (MO)-based LLCNPs with various stabilizers (F127, F108, and Tween 80) and phytantriol (PT)-F127 cubosomes were produced at various flow conditions via a bottom-up method using a microfluidic platform. FINDINGS: This simple enabling strategy was used to formulate LLCNPs with lower polydispersity compared to the traditional top-down homogenization method. Significantly, particle size could be quantitatively controlled by varying the overall flow-rate; a scaling law was identified between nanoparticle mean size and the total flow rate (Q) of meansize∼Q-0.15 for MO cubosomes and meansize∼Q-0.19 for PT cubosomes (at a fixed flow rate ratio). Effective size control was achieved for a range of cubosome formulations involving different lipids and stabilizers. The formulation of stable, drug-loaded cubosomes with high encapsulation efficiency using this method was exemplified using calcein as a model drug. This work will further promote the utilisation of LLCNPs in nanomedicine and facilitate their clinical translation.

Ice crystallization under cryogenic cooling in lipid membrane nanoconfined geometry: Time-resolved structural dynamics.

Time-resolved structural investigations of crystallization of water in lipid/protein/salt mesophases at cryogenic temperatures are significant for comprehension of ice nanocrystal nucleation kinetics in lipid membranous systems and can lead to a better understanding of how to experimentally retard the ice formation that obstructs the protein crystal structure determination. Here, we present a time-resolved synchrotron microfocus X-ray diffraction (TR-XRD) study based on ∼40,000 frames that revealed the dynamics of water-to-ice crystallization in a lipid/protein/salt mesophase subjected to cryostream cooling at 100 K. The monoolein/hemoglobin/salt/water system was chosen as a model composition related to protein-loaded lipid cubic phases (LCP) broadly used for the crystallization of proteins. Under confinement in the nanoscale geometry, metastable short-living cubic ice (Ic) rapidly crystallized well before the formation of hexagonal ice (Ih). The detected early nanocrystalline states of water-to-ice transformation in multicomponent systems are relevant to a broad spectrum of technologies and understanding of natural phenomena, including crystallization, physics of water nanoconfinement, and rational design of anti-freezing and cryopreservation systems.

Development and optimization of amphiphilic self-assembly into nanostructured liquid crystals for transdermal delivery of an antidiabetic SGLT2 inhibitor.

The anti-hyperglycemic sodium glucose co-transporter 2 inhibitor Canagliflozin (CFZ) represents a recent antihyperglycemic modality, yet it suffers from low oral bioavailability. The current work aims to formulate CFZ-loaded transdermal nanostructured liquid crystal gel matrix (NLCG) to improve its therapeutic efficiency. Pre-formulation study included the construction of pseudoternary phase diagrams to explore the effect of two conventional amphiphiles against amphiphilic tri-block copolymer in the formulation of NLCG. The influence of different co-solvents was also investigated with the use of monooleine as the oil. Physical characterization, morphological examination and skin permeation were performed for the optimized formulations. The formula of choice was further investigated for skin irritation and chemical stability. Pharmacodynamic evaluation of the successful formula was conducted on hyperglycemic as well as normoglycemic mice. In addition, oral glucose tolerance test was conducted. Results revealed the supremacy of Poloxamer for stabilizing and maximizing liquid crystal gel (LCG) area percentage that reached up to 12.6%. CFZ-NLCG2 isotropic formula showed the highest permeation parameters; maximum flux value of 7460 µg/cm2 h and Q24 of 5327 µg/cm2. Pharmacodynamic evaluation revealed the superiority of the antihyperglycemic activity of CFZ-NLCG2 in fasting mice and its equivalence in the oral glucose tolerance test (OGTT) compared to the oral one. The obtained results confirmed the success of CFZ-NLCG2 in the transdermal delivery of CFZ in therapeutically effective concentration compared to the oral route, bypassing first pass effect; in addition, eliminates the possible gastrointestinal side effects related to the inhibition of intestinal sodium glucose co-transporter (SGLT) and maximizes its selectivity to the desired inhibition of renal SGLT.

Effect of Glyceryl Monoolein Addition on the Foaming Properties and Stability of Whipped Oleogels.

Medium Chain Triglyceride (MCT) oil was successfully combined with Glyceryl Monostearate (GMS) and Glyceryl Monoolein (GMO) to form oleogels that were subsequently whipped to form stable oleofoams. The co-crystallization of GMS and GMO at a ratio of 20:1, 20:2.5, and 20:5 within MCT oil was studied through Differential Scanning Calorimetry (DSC), X-ray Diffraction analysis (XRD), rheological analysis, Fluorescence Recovery after Photobleaching (FRAP), Fourier Transform Infrared Spectroscopy (FTIR), and polarized microscopy. The addition of 5% GMO resulted in the production of more stable oleogels in terms of crystal structure and higher peak melting point, rendering this formulation suitable for pharmaceutical applications that are intended to be used internally and those that require stability at temperatures close to 40 °C. All formulations were whipped to form oleofoams that were evaluated for their storage stability for prolonged period at different temperatures. The results show that oleofoams containing 5% MGO retained their foam characteristics even after 3 months of storage under different temperature conditions.

Advances and applications of monoolein as a novel nanomaterial in mitigating chronic lung diseases.

Chronic lung diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, and the recently emerged COVID-19, are a huge threat to human health, and among the leading causes of global morbidity and mortality every year. Despite availability of various conventional therapeutics, many patients remain poorly controlled and have a poor quality of life. Furthermore, the treatment and diagnosis of these diseases are becoming increasingly challenging. In the recent years, the application of nanomedicine has become increasingly popular as a novel strategy for diagnosis, treatment, prevention, as well as follow-up of chronic lung diseases. This is attributed to the ability of nanoscale drug carriers to achieve targeted delivery of therapeutic moieties with specificity to diseased site within the lung, thereby enhancing therapeutic outcomes of conventional therapies whilst minimizing the risks of adverse reactions. For this instance, monoolein is a polar lipid nanomaterial best known for its versatility, thermodynamic stability, biocompatibility, and biodegradability. As such, it is commonly employed in liquid crystalline systems for various drug delivery applications. In this review, we present the applications of monoolein as a novel nanomaterial-based strategy for targeted drug delivery with the potential to revolutionize therapeutic approaches in chronic lung diseases.

Application of Fluconazole-Loaded pH-Sensitive Lipid Nanoparticles for Enhanced Antifungal Therapy.

Cryptococcus neoformans is a yeast-like fungus that can cause the life-threatening disease cryptococcal meningitis. Numerous reports have shown increased resistance of this fungus against antifungal treatments, such as fluconazole (Fluc), contributing to an 80% global mortality rate. This work presents a novel approach to improve the delivery of the antifungal agent Fluc and increase the drug's targetability and availability at the infection site. Exploiting the acidic environment surrounding a C. neoformans infected site, we have developed pH-sensitive lipid nanoparticles (LNP) encapsulating Fluc to inhibit the growth of resistant C. neoformans. The LNP-Fluc delivery system consists of a neutral lipid monoolein (MO) and a novel synthetic ionizable lipid 2-morpholinoethyl oleate (O2ME). At neutral pH, because of the presence of O2ME, the nanoparticles are neutral and exhibit a liquid crystalline hexagonal nanostructure (hexosomes). At an acidic pH, they are positively charged with a cubic nanostructure (cubosomes), which facilitates the interaction with the negatively charged fungal cell wall. This interaction results in the MIC50 and MIC90 values of the LNP-Fluc being significantly lower than that of the free-Fluc control. Confocal laser scanning microscopy and scanning electron microscopy further support the MIC values, showing fungal cells exposed to LNP-Fluc at acidic pH were heavily distorted, demonstrating efflux of cytoplasmic molecules. In contrast, fungal cells exposed to Fluc alone showed cell walls mostly intact. This current study represents a significant advancement in delivering targeted antifungal therapy to combat fungal antimicrobial resistance.

Observations of phase changes in monoolein during high viscous injection.

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations.

Influence of seasonality on the physicochemical properties of Moringa oleifera Lam. Seed oil and their oleochemical potential.

The effect of abiotic factors, such as weather and climate can alter the properties of vegetable oils. In this work, the effects of the refining process and pre-drying of Moringa oleifera Lam. seeds collected in the dry and rainy seasons (seasonality) were evaluated on the characteristics of the extracted oils. The refined and crude dry season oils had lower acidity and moisture content than the dry and raw rainy season oils. Oleic acid (C18:1) showed the highest concentration in the different Moringa oils studied. The results suggest that dry season oils are more suitable for application as feedstocks in the cosmetic, food, medicinal and pharmaceutical industries. Furthermore, refining proved to be efficient in removing free fatty acids and in lightening the oil.

Lipid vesicular gels for topical administration of antioxidants.

The application of a formulation on the skin represents an effective way to deliver bio-active molecules for therapeutical purposes. Moreover, the outermost skin layer, the stratum corneum, can be overcome by employing chemical permeation enhancers and edge activators as components. Several lipids can be considered as permeation enhancers, such as the ubiquitous monoolein, one of the most used building blocks for the preparation of lipid liquid crystalline nanoparticles which are applied as drug carriers for nanomedicine applications. Recent papers highlighted how bile salts can affect the phase behavior of monoolein to obtain drug carriers suitable for topical administration, given their role as edge activators into the formulation. Herein, the encapsulation of natural antioxidants (caffeic acid and ferulic acid) into lipid vesicular gels (LVGs) made by monoolein and sodium taurocholate (TC) in water was studied to produce formulations suitable for topical application. TC induces a bicontinuous cubic to multilamellar phase transition for monoolein in water at the given concentrations, and by increasing its content into the formulations, unilamellar LVGs are formed. The encapsulation of the two antioxidants did not affect significantly the structure of the gels. The oscillating rheological studies showed that ferulic acid has a structuring effect on the lipid matrix, in comparison with the empty dispersion and the one containing caffeic acid. These gels were then tested in vitro on new-born pig skin to evaluate their efficacy as drug carriers for topical administration, showing that caffeic acid is mostly retained in the gel whereas ferulic acid is released at a higher degree. The data herein reported provide some further information on the effect of bile salts on the lipid self-assembly to evaluate useful compositions for topical administration of natural antioxidants.

Antioxidant-containing monoolein aqueous dispersions: a preliminary study.

The present study describes a preliminary study on the use of monoolein aqueous dispersions (MADs) as delivery systems for antioxidant molecules, namely, ascorbyl palmitate (AP) and alpha-tocopherol (AT). MAD, produced by emulsifying monoolein (4.5% w/w) in water and poloxamer 407 (0.5% w/w) as emulsifier, was characterized in terms of size, morphology, and antioxidant activity by mean of PCS, cryo-TEM, and (2,2-diphenyl-1-picrylhydrazyl) assay. MAD-AP or MAD-AT gave rise to a bimodal size distribution with mean size around 200 nm. All the preparations stored at 25 °C showed quite stable size at least up to 90 days. Cryo-TEM images confirmed MAD size distribution and indicated different MAD morphologies as a function of the loaded antioxidant molecule. Indeed, in the case of MAD-AP, vesicles and cubosomes with the typical inner cubic structure were observed, while vesicles and hexosomes were shown for MAD-AT. The encapsulation efficiency of both antioxidants reached more than 90% with respect to the total amount of drug used for MAD preparation. Moreover, AP and AT antioxidant activity was retained after encapsulation, and in vitro Franz cell experiments showed that the MAD enabled to better control the drug release. These preliminary results suggest that MAD formulations could be further investigated as a potential delivery system for antioxidant supplementation in dietary or cosmetic fields.

Stability, flow alignment and a phase transition of the lipidic cubic phase during continuous flow injection.

Continuous flow injection is a key technology for serial crystallography measurements of protein crystals suspended in the lipidic cubic phase (LCP). To date, there has been little discussion in the literature regarding the impact of the injection process itself on the structure of the lipidic phase. This is despite the fact that the phase of the injection matrix is critical for the flow properties of the stream and potentially for sample stability. Here we report small-angle X-ray scattering measurements of a monoolein:water mixture during continuous delivery using a high viscosity injector. We observe both an alignment and modification of the LCP as a direct result of the injection process. The orientation of the cubic lattice with respect to the beam was estimated based on the anisotropy of the diffraction pattern and does not correspond to a single low order zone axis. The solvent fraction was also observed to impact the stability of the cubic phase during injection. In addition, depending on the distance traveled by the lipid after exiting the needle, the phase is observed to transition from a pure diamond phase (Pn3m) to a mixture containing both gyriod (Ia3d) and lamellar (Lα) phases. Finite element modelling of the observed phase behaviour during injection indicates that the pressure exerted on the lipid stream during extrusion accounts for the variations in the phase composition of the monoolein:water mixture.