Efficacy of stem cell secretome loaded in hyaluronate sponge for topical treatment of psoriasis.

Psoriasis vulgaris is an inflammatory disease characterized by distinctive skin lesions and dysregulated angiogenesis. Recent research uses stem cell secretion products (CM); a set of bioactive factors with therapeutic properties that regulate several cellular processes, including tissue repair and angiogenesis. The aim of this work was to evaluate the effect of CM of Wharton's gelatin MSC (hWJCM) in a treatment based on the bioactivation of a hyaluronic acid matrix (HA hWJCM) in a psoriasiform-like dermatitis (PD) mouse model. A preclinical study was conducted on PD mice. The effect of hWJCM, Clobetasol (Clob) gold standard, HA Ctrl, and HA hWJCM was tested topically evaluating severity of PD, mice weight as well as skin, liver, and spleen appearance. Treatment with either hWJCM, HA Ctrl or HA hWJCM, resulted in significant improvement of the PD phenotype. Moreover, treatment with HA hWJCM reduced the Psoriasis Area Severity Index (PASI), aberrant angiogenesis, and discomfort associated with the disease, leading to total recovery of body weight. We suggest that the topical application of HA hWJCM can be an effective noninvasive therapeutic solution for psoriasis, in addition to other skin diseases, laying the groundwork for future studies in human patients.

Encapsulation of Cochleates Derived from Salmonella Infantis with Biopolymers to Develop a Potential Oral Poultry Vaccine.

The aim of this study was to develop and characterize Salmonellaenterica serovar Infantis (S. Infantis) cochleates protected by encapsulation technology as a potential vaccine and to determine its safety in pullets. Cochleates were encapsulated by two technologies, spray drying and ionotropic gelation at different concentrations (0-15% v/v), and were characterized by physicochemical properties, protein content and Fourier Transform Infrared Spectroscopy (FTIR). The cochleates were white liquid suspensions with tubular shapes and a protein content of 1.0-2.1 mg/mL. After encapsulation by spray drying, microparticles ranged in size from 10.4-16.9 µm, were spherical in shape, and the protein content was 0.7-1.8 mg/g. After encapsulation by ionotropic gelation, beads ranged in size from 1620-1950 µm and were spherical in shape with a protein content of 1.0-2.5 mg/g. FTIR analysis indicated that both encapsulation processes were efficient. The cochleates encapsulated by ionotropic gelation were then tested for safety in pullets. No ill effect on the health of animals was observed upon physical or postmortem examination. In conclusion, this study was the first step in developing a potential oral S. Infantis vaccine safe for poultry using a novel cochleate encapsulation technology. Future studies are needed to determine the effectiveness of the vaccine.

House fly (Musca domestica) larvae meal as an ingredient with high nutritional value: Microencapsulation and improvement of organoleptic characteristics.

Insects have potential to become food ingredients, but it is necessary to improve the sensory properties of insects to help them to be better accepted by the population. The purpose of this study was to produce and characterize house fly larval meal (FLM) converted to a micro-encapsulated powder to improve appearance and other organoleptic characteristics. FLM showed high protein (54%) and lipid (22%) content, with a microbiological activity compatible for food purposes. Moreover, the high content of essentials amino acids (lysine, cysteine and leucine) and unsaturated fatty acids (oleic, linoleic and palmitoleic) make FLM a valuable nutritional source. Spray drying was selected to encapsulate FLM (0.5-2% w/v) using maltodextrin (20% w/v) and alginate (0.5% w/v). Encapsulation improved the appearance of FLM, creating a white-beige, monodispersed micro-powder (9 µm in size). Micro-powder with 2% FLM is considered a good source of protein (5.1%). Microencapsulation also dramatically reduced the volatile emissions of FLM. In conclusion, novel FLM micro-powders were developed using a simple and scalable encapsulation technique. The micro-powder with 2% FLM is a good source of protein, has a pleasant appearance similar to vegetable meals and has improved odor compared to typical insect meals. Thus, insect-based food ingredients in micro-powders could become more accepted by the general population.

The key role of the drug self-aggregation ability to obtain optimal nanocarriers based on aromatic-aromatic drug-polymer interactions.

The efficient association and controlled release of hydrophilic and aromatic low molecular-weight drugs (HALMD) still remains a challenge due to their relatively weak interactions with excipients and strong affinity to water. Considering that a wide variety of drugs to treat chronic diseases are HALMD, their inclusion in polymeric nanoparticles (NPs) constitutes an attractive possibility by providing to these drugs with controllable physiochemical properties, preventing crisis episodes, decreasing dose-dependent side effects and promoting therapeutic adhesiveness. However, the strong interaction of HALMD with the aqueous medium jeopardizes their encapsulation and controlled release. In this work, the role of the self-assembly tendency of HALMD on their association with the aromatic excipient poly(sodium 4-styrensulfonate) (PSS) to form NPs is studied. For this aim, the widely used drugs amitriptyline (AMT), promethazine (PMZ), and chlorpheniramine (CPM) are selected due to their well described critical aggregation concentration (cac) (36 mM for AMT, 36 mM for PMZ, and 69.5 mM for CPM). These drugs undergo aromatic-aromatic interactions with the polymer, which stabilize their mutual binding, as seen by NMR. The simple mixing of solutions of opposite charged molecules (drug + PSS) allowed obtaining NPs. Importantly, comparing the three drugs, the formation of NPs occurred at significantly lower absolute concentration and significantly lower drug/polymer ratio as the cac takes lower values, indicating a stronger binding to the polymer, as also deduced from the respective drug/polymer dissociation constant values. In addition, the number of formed NPs is similar for all formulations, even though a much lower concentration of the drug and polymer is present in systems comprising lower cac. The obtained NPs are spheroidal and present size between 100 and 160 nm, low polydispersity (≤0.3) and negative zeta potential (from -30 to -60 mV). The association efficiency reaches values ≥ 83% and drug loading could achieve values up to 68% (never evidenced before for systems comprising HALMD). In addition, drug release studies are also significantly influenced by cac, providing more prolonged release for AMT and PMZ (lower cac), whose delivery profiles adjust to the Korsmeyer-Peppas equation. As a novelty of this work, a synergic contribution of drug self-association tendency and aromatic-aromatic interaction between the drug and polymers is highlighted, a fact that could be crucial for the rational design and development of efficient drug delivery systems.

Light-induced release of the cardioprotective peptide angiotensin-(1-9) from thermosensitive liposomes with gold nanoclusters.

Angiotensin-(1-9), a component of the non-canonical renin-angiotensin system, has a short half-life in blood. This peptide has shown to prevent and/or attenuate hypertension and cardiovascular remodeling. A controlled release of angiotensin-(1-9) is needed for its delivery to the heart. Our aim was to develop a drug delivery system for angiotensin-(1-9). Thermosensitive liposomes (LipoTherm) were prepared with gold nanoclusters (LipoTherm-AuNC) to increase the stability and reach a temporal and spatial control of angiotensin-(1-9) release. Encapsulation efficiencies of nearly 50% were achieved in LipoTherm, reaching a total angiotensin-(1-9) loading of around 180 µM. This angiotensin-(1-9)-loaded LipoTherm sized around 100 nm and exhibited a phase transition temperature of 43 °C. AuNC were grown on LipoTherm and the new hybrid nanosystem showed energy absorption in the near-infrared (NIR) wavelength range. By NIR laser irradiation, a controlled release of angiotensin-(1-9) was achieved from the LipoTherm-AuNC nanosystem. These nanosystems did not show any cytotoxic effect on cultured cardiomyocytes. Biological activity of angiotensin-(1-9) released from the LipoTherm-AuNC-based nanosystem was confirmed using an ex vivo Langendorff heart model.

Ionic Nanocomplexes of Hyaluronic Acid and Polyarginine to Form Solid Materials: A Green Methodology to Obtain Sponges with Biomedical Potential.

We report on the design, development, characterization, and a preliminary cellular evaluation of a novel solid material. This material is composed of low-molecular-weight hyaluronic acid (LMWHA) and polyarginine (PArg), which generate aqueous ionic nanocomplexes (INC) that are then freeze-dried to create the final product. Different ratios of LMWHA/PArg were selected to elaborate INC, the size and zeta potential of which ranged from 100 to 200 nm and +25 to -43 mV, respectively. Turbidimetry and nanoparticle concentration analyses demonstrated the high capacity of the INC to interact with increasing concentrations of LMWHA, improving the yield of production of the nanostructures. Interestingly, once the selected formulations of INC were freeze-dried, only those comprising a larger excess of LMWHA could form reproducible sponge formulations, as seen with the naked eye. This optical behavior was consistent with the scanning transmission electron microscopy (STEM) images, which showed a tendency of the particles to agglomerate when an excess of LMWHA was present. Mechanical characterization evidenced low stiffness in the materials, attributed to the low density and high porosity. A preliminary cellular evaluation in a fibroblast cell line (RMF-EG) evidenced the concentration range where swollen formulations did not affect cell proliferation (93-464 µM) at 24, 48, or 72 h. Considering that the reproducible sponge formulations were elaborated following inexpensive and non-contaminant methods and comprised bioactive components, we postulate them with potential for biomedical purposes. Additionally, this systematic study provides important information to design reproducible porous solid materials using ionic nanocomplexes.

A New Methodology to Create Polymeric Nanocarriers Containing Hydrophilic Low Molecular-Weight Drugs: A Green Strategy Providing a Very High Drug Loading.

To date, a large number of active molecules are hydrophilic and aromatic low molecular-weight drugs (HALMD). Unfortunately, the low capacity of these molecules to interact with excipients and the fast release when a formulation containing them is exposed to biological media jeopardize the elaboration of drug delivery systems by using noncovalent interactions. In this work, a new, green, and highly efficient methodology to noncovalently attach HALMD to hydrophilic aromatic polymers to create nanocarriers is presented. The proposed method is simple and consists in mixing an aqueous solution containing HALMD (model drugs: imipramine, amitriptyline, or cyclobenzaprine) with another aqueous solution containing the aromatic polymer [model polymer: poly(sodium 4-styrenesulfonate) (PSS)]. NMR experiments demonstrate strong chemical shifting of HALMD aromatic rings when interacting with PSS, evidencing aromatic-aromatic interactions. Ion pair formation and aggregation produce the collapse of the system in the form of nanoparticles. The obtained nanocarriers are spheroidal, their size ranging between 120 and 170 nm, and possess low polydispersity (≤0.2) and negative zeta potential (from -60 to -80 mV); conversely, the absence of the aromatic group in the polymer does not allow the formation of nanostructures. Importantly, in addition to high drug association efficiencies (≥90%), the formed nanocarriers show drug loading values never evidenced for other systems comprising HALMD, reaching ≈50%. Diafiltration and stopped flow experiments evidenced kinetic drug entrapment governed by molecular rearrangements. Importantly, the nanocarriers are stable in suspension for at least 18 days and are also stable when exposed to different high ionic strength, pH, and temperature values. Finally, they are transformable to a reconstitutable dry powder without losing their original characteristics. Considering the large quantity of HALMD with importance in therapeutics and the simplicity of the presented strategy, we envisage these results as the basis to elaborate a number of drug delivery systems with applications in different pathologies.

Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin.

Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit® RLPO (ERL) NPs showed smaller particle diameters (245 ± 2 nm) and better redispersibility after freeze-drying than either poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.