Safety assessment of starch-based personal care products: Nanocapsules and pickering emulsions.

The safety profile of the ingredients used in topical dosage forms and its evaluation is an issue of utmost importance. A suitable equilibrium between safety and efficacy is crucial before promoting a dermatological product. The aim of this work was to assess the safety and biological effects of starch-based vehicles (St-BV) used in such products. The hazard, exposure and dose-response assessment were used to characterize the risk of each ingredient. The EpiSkin™ assay and human repeat insult patch tests were performed to compare the theoretical safety assessment to in vitro and in vivo data. The efficacy of the St-BV was studied using biophysical measurements in human volunteers during 28 days, showing that all ingredients and their combinations were safe for the consumer. Tissue viability determined using the EpiSkin™ testing reached values between 84.0 ±â€¯5.0% and 98.0 ±â€¯8.6% after application of St-BV, which were considered as non-irritant to the skin. These observations were confirmed by the in vivo studies where the St-BV did not induce any sensitization on the volunteers, being safe for human use. Moreover, St-BV increased skin hydration and microcirculation, emerging as an attractive alternative to chemical raw materials.

Design of minocycline-containing starch nanocapsules for topical delivery.

Pharmaceutical research has been focussed on developing improved delivery systems while exploring new ways of using approved excipients. The present work investigated the potential of starch nanocapsules (StNC) as a topical delivery platform for hydrophilic antimicrobial drugs using minocycline hydrochloride (MH) as a model drug. Thus, a quality by design approach was used to assess the role of different factors that affect the main pharmaceutical properties of StNC prepared using an emulsification-solvent evaporation method. Full characterisation was performed in terms of particle size, encapsulation efficiency, morphology and physical stability at 5 ± 3 °C. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. The MH loading only promoted minor changes upon StNC properties. Formulations were stable without variations on physicochemical properties. All tested formulations presented a zeta-potential of +33.6 ± 6.7 mV, indicating a good physical stability and evidencing that StNC are suitable nanocarriers for topical use.

Emollients in dermatological creams: Early evaluation for tailoring formulation and therapeutic performance.

The targeted choice of the emollient of a cream determines its physicochemical properties and clinical effectiveness. This work researched the effects of emollient properties on the final characteristics and potential performance of oil-in-water dermatological creams. Seven emollients with different chemical characteristics and structures (alkane, triglyceride, ether, silicone, vegetable oils, and mineral oil) were tested in a model formulation. Early stability, pH, droplet size distribution, rheology, tackiness, adhesivity, spreadability, tribology, and release profile of a lipophilic substance model (in Franz cells, through a synthetic membrane, for six hours) were assessed. The creams had acid epicutaneous pH and a "shear-thinning" "solid-like" viscoelastic behavior. Among the seven emollients' properties, polarity, density, and viscosity were the most influential. Droplet parameters were the most impacted, pH and release were moderately affected, and the textural properties were lowly to moderately impacted. The emollient substitution in the model formulation affected the experimental parameters differently, allowing formulation optimization and tailoring its potential therapeutic performance regarding drug release, coadjutant effects, and dwell time on the skin. By looking at the creams' characteristics, it was possible to select the best-suited emollients for releasing a lipophilic drug, applying on painful skin, and formulation in wash-off products or leave-on protective barrier creams.

Use of pulp mill inorganic wastes as alternative liming materials.

A laboratory aerobic incubation study was performed during 18 weeks under controlled conditions to assess the effects of applying different doses of pulp mill inorganic wastes on the physical-chemical properties of an acid Dystric Cambissol. Three different inorganic wastes were tested - wood ash, dregs and grits, and an agriculture limestone was used as reference. Results showed that increasing the dose applied of the different inorganic wastes tested always led to significant raises of soil pH at different incubation times demonstrating that its use as alternative-liming materials could be a valid and less expensive option to the use of commercial agricultural limestone. Moreover, no immediate concerns seem to be expected related to soil exchangeable sodium (Na) content, at least for the doses needed to increase soil pH until the targeted value 6.5. Particularly for wood ash a pronounced increase on soil extractable potassium and phosphorous was observed, indicating that besides the liming effect this waste can contribute to improve soil fertility by supplying significant available amounts of these nutrients. Finally, metals do not seem to be a limiting factor for the application to land of these by-products.

Starch nanocapsules containing a novel neutrophil elastase inhibitor with improved pharmaceutical performance.

Psoriasis and atopic dermatitis patients show an excessive amount of elastase in peripheral blood neutrophils due to an imbalance between this proteolytic enzyme and its endogenous inhibitors, the search for new human neutrophil elastase (HNE) inhibitors are required. The HNE is an attractive therapeutic target and inhibitors with new molecular architectures have been extensively investigated. In this context a promising novel synthetic human neutrophil elastase inhibitor (ER143) was associated to a starch-based nanoparticulate system (StNC) with improved pharmaceutical performance, using a quality by design approach to support product development and optimization. The resulting formulation was characterized in terms of and in vitro release, permeation and retention studies in newborn pig skin, using Franz diffusion cells revealing the StNC have the ability to control the drug release rate and contribute to a high skin retention and/or permeation profiles. The anti-inflammatory activity accessed in vivo using the croton oil-induced ear inflammation model in mice showed that erythema and edema were attenuated in 98% following local application. These observations suggest the association of ER143 to the StNC promotes a deeper skin penetration and retention, also confirming StNC as a potential topical delivery system.

Study of biochemical and microbiological parameters during composting of pine and eucalyptus bark.

To study the possibility of some residues from pulp and paper industry being used as substrates to produce seedlings in containers, three composting experiments were carried out using eucalyptus bark, pine bark and a mixture (60:40, v:v) of pine bark+eucalyptus bark. Biochemical parameters studied were: acid and alkaline phosphatases, lipase (C10), protease, urease, beta-glucosidase and total cellulases. The microbiological populations of total aerobic bacteria, total fungi, actinomycetes, nitrifying bacteria, cellulolytic bacteria and fungi were also evaluated. At the end of the process physicochemical characterization of composts was also performed. Results showed in general that the highest microbiological populations as well as for enzymatic activities occurred during the thermophilic phase (>40 degrees C) of the process. On the other hand and according to the physicochemical characteristics of composts pine bark is the most appropriate material to be used in the formulation of substrates to produce plants in containers.

Evaluation of a compost obtained from forestry wastes and solid phase of pig slurry as a substrate for seedlings production.

A composted material obtained from forestry wastes and solid phase of pig slurry was evaluated as a substrate component for the production of tomato and lettuce seedlings. Four different substrates were tested: compost (100C), a mixture of 75% compost and 25% peat substrate (75C), a mixture of 50% compost and 50% peat substrate (50C), and peat-based substrate (control). Compost increased the pH of the substrate from 6.3 (control) to 6.9 (100C) but did not affect the electrical conductivity (0.26 and 0.27 mScm(-1), respectively, for control and 100C). Germination and growth of lettuce seedlings were not affected by the substrate type, contrasting with tomato seedlings where the highest growth occurred at 100C substrate. Increasing compost percentage on substrate increased nitrogen, calcium and magnesium availability and, consequently, the concentration of these elements in plant tissues increased. On the contrary, potassium and manganese concentration decreased. Results from the study suggest that the compost studied is a good alternative to peat-based substrates for the production of vegetable seedlings.

Design of novel starch-based Pickering emulsions as platforms for skin photoprotection.

Green coffee oil and modified starch were recently found to have an enhanced protection effect against UV radiation. Therefore, this work aimed to develop an innovative sunscreen formulation based on Pickering emulsions concept, i.e., surfactant-free emulsions stabilized by physical UV filters associated natural oils as a key strategy for prevention against UV-induced skin damage. The Pickering emulsions of different compositions were characterized in terms of pH, mechanical, physical and microbiological stability by a thorough pharmaceutical control. In addition, the sun protection factor (SPF) as well as the in vitro and in vivo biological properties of the final formulations, including Episkin®, HRIPT and sunscreen water resistance. Formulation studies demonstrated the addition of physical UV filters was beneficial, leading to the inclusion of ZnO and TiO2 to ensure a high SPF against UVA and UVB, respectively. Although starch particles presented no intrinsic photoprotection properties, they proved to be a SPF promoter by a synergistic effect. Green coffee oil was the selected natural oil due to the highest SPF, when compared to other natural oils tested. Besides the excellent sunscreen activity confirmed by in vitro and in vivo results, the final formulations proved to be also suitable for topical use according to the rheological assessment and stability throughout the study period (3months). In conclusion, the combination of three multifunctional solid particles and green coffee oil, contributed to achieve a stable and effective innovative sunscreen with a wide range of UV radiation protection.

A Quality by design (QbD) approach on starch-based nanocapsules: A promising platform for topical drug delivery.

Exploring novel applications for approved excipients with a history of safe use in therapeutics is a smart strategy to obtain improved pharmaceutical products. The present study aimed at developing a novel starch-based nanoparticulate carrier system (StNC) for topical delivery of lipophilic bioactive molecules. The role of the different factors that affect the particle size distribution and zeta potential of StNC prepared by the emulsification-solvent evaporation method was assessed using a quality by design approach. An optimal formulation was selected and fully characterized in terms of molecular interactions (DSC and FTIR), morphology (TEM and AFM), as well as in vitro and in vivo biological properties, including biological sensitivity/irritation studies performed in human volunteers. Results show the surfactant and lipid contents play a major role in StNC particle size distribution. In addition, all tested formulations presented a zeta potential of ca. +33.6±6.7 mV, indicating a good physical stability, while revealing an excellent compromise between stability, safety and cosmeticity, evidencing that StNC are suitable nanocarriers for topical use. Finally, the design planning methodology has clearly shown its usefulness for optimizing the formulation, being also crucial for the understanding of StNC formation process. The StNC proved to be a promising formulation strategy and a potential nanocarrier for topical lipophilic bioactive molecules.

Starch-based Pickering emulsions for topical drug delivery: A QbD approach.

Pickering emulsions are stabilized by solid particles instead of surfactants and have been widely investigated in pharmaceutical and cosmetic fields since they present less adverse effects than the classical emulsions. A quality by design (QbD) approach was applied to the production of w/o emulsions stabilized by starch. A screening design was conducted to identify the critical variables of the formula and the process affecting the critical quality properties of the emulsion (droplet size distribution). The optimization was made by establishing the Design Space, adjusting the concentration of starch and the quantity of the internal aqueous phase. The emulsion production process was, in turn, adjusted by varying the time and speed of stirring, to ensure quality and minimum variability. The stability was also investigated, demonstrating that an increase in starch concentration improves the stability of the emulsion. Rheological and mechanical studies indicated that the viscosity of the emulsions was enhanced by the addition of starch and, to a higher extent, by the presence of different lipids. The developed formulations was considered non-irritant, by an in vitro assay using human cells from skin (Df and HaCat) with the cell viability higher than 90% and, with self-preserving properties. Finally, the QbD approach successfully built quality in Pickering emulsions, allowing the development of hydrophilic drug-loaded emulsions stabilized by starch with desired organoleptic and structural characteristics. The results obtained suggest that these systems are a promising vehicle to be used in products for topical administration.

Thermodynamic characterisation of the mutated isoenzyme A of beta-N-acetylhexosaminidase in GM2-gangliosidosis B1 variant.

Here we report the determination of the activation energies of the plasma isoenzymes of beta-N-acetylhexosaminidase (Hex, EC 3.2.1.52), isolated by chromatography in DEAE-cellulose, using the neutral chromogenic substrate 3,3'dichlorophenylsulfonphthaleinyl-N-acetyl-beta-D-glucosaminide. The activation energy of mutated Hex A isoenzyme (Ea approximately 71.5 kJ/mol) from a patient with GM2-gangliosidosis B1 variant, homozygote for the G533-->A (Arg178His) mutation, was significantly higher than that of normal Hex A (Ea approximately 41.8 kJ/mol) and analogous to that of Hex B isoenzyme (Ea approximately 75.1 kJ/mol). The determination of this thermodynamic variable of Hex in different biological specimens could allow for a straightforward biochemical characterisation of the GM2-gangliosidosis B1 variant.

Structure and rheology of semisolid o/w creams containing cetyl alcohol/non-ionic surfactant mixed emulsifier and different polymers.

Oil-in-water (o/w) emulsions for cosmetic use, such as lotions and creams, are complex multiple-phase systems, which may contain a number of interacting surfactants, fatty amphiphiles, polymers and other excipients. This study investigates the influence of two synthetic cationic polymers, Polyquaternium-7 and Polyquaternium-11, and the natural anionic polymer, gum of acacia, on the rheology and microstructure of creams prepared with a non-ionic mixed emulsifier (cetyl stearyl alcohol-12EO/cetyl alcohol) using rheology (continuous shear, and viscoelastic creep and oscillation), microscopy and differential scanning calorimetry (DSC). A control cream containing no polymer was also investigated. The semisolid control cream was structured by a swollen lamellar gel network phase formed from the interaction of cetyl alcohol and the POE surfactant, in excess of that required to stabilize oil droplets, with continuous phase water. Endothermic transitions between 25 and 100 degrees C were identified as components of this phase. Incorporation of cationic polymer into the formulation caused significant loss of structure to produce a mobile semisolid containing larger oil droplets. The microscopical and thermal data implied that the cationic polymer caused the swollen lamellar gel network phase to transform into non-swollen crystals of cetyl alcohol. In contrast, incorporation of gum of acacia produced a thicker cream than the control, with smaller droplet sizes and little evidence of the gel network. Microscopical and thermal data implied that although there were also interactions between gum of acacia and both the surfactant and the swollen gel network phase, the semisolid properties were probably because of the ability of the gum of acacia to stabilize and thicken the emulsion in the absence of the swollen lamellar network.

Characterization of the isoenzyme profile of beta-N-acetylhexosaminidase in the urine of newborns.

The urinary isoenzymes of beta-N-acetylhexosaminidase (Hex) in newborn infants were characterised by chromatography, electrophoresis, thermodynamic analysis and through substrate specificity. No qualitative difference was found for the major Hex A and Hex B isoenzymes between full-term or premature newborns and adults, although in the latter group the relative proportion of Hex B is much lower (18.5 +/- 2.7% vs. 36.3 +/- 1.0%). An additional minor enzyme form was found in some premature newborns, which eluted from the DEAE-cellulose column at a higher concentration of NaCl than Hex A and, like this isoenzyme, is able to hydrolyse 4-methylumbellipheryl-2-acetamido-2-deoxy-beta-D-glucopyranoside-6 -sulphate, which would suggest that it has alpha subunits in its molecule. These results do not confirm the hypothesis of other authors about the existence of a unique fetal Hex isoenzyme in neonatal urine which eluted before the application of the NaCl gradient, similarly to the Hex B.