The Optimization of Pressure-Assisted Microsyringe (PAM) 3D Printing Parameters for the Development of Sustainable Starch-Based Patches.

The aim of this work was to develop sustainable patches for wound application, using the biopolymer starch, created using a low-cost 3D printing PAM device. The composition of a starch gel was optimized for PAM extrusion: corn starch 10% w/w, ß-glucan water suspension (filler, 1% w/w), glycerol (plasticizer, 29% w/w), and water 60% w/w. The most suitable 3D printing parameters were optimized as well (nozzle size 0.8 mm, layer height 0.2 mm, infill 100%, volumetric flow rate 3.02 mm3/s, and print speed 15 mm/s). The suitable conditions for post-printing drying were set at 37 °C for 24 h. The obtained patch was homogenous but with low mechanical resistance. To solve this problem, the starch gel was extruded over an alginate support, which, after drying, becomes an integral part of the product, constituting the backing layer of the final formulation. This approach significantly improved the physicochemical and post-printing properties of the final bilayer patch, showing suitable mechanical properties such as elastic modulus (3.80 ± 0.82 MPa), strength (0.92 ± 0.08 MPa), and deformation at break (50 ± 1%). The obtained results suggest the possibility of low-cost production of patches for wound treatment by additive manufacturing technology.

Polymeric Patches Based on Chitosan/Green Clay Composites and Hazelnut Shell Extract as Bio-Sustainable Medication for Wounds.

Hazelnut shells, the main waste deriving from hazelnut processing, represent an interesting source of active molecules useful in pharmaceutics, although they have not yet been examined in depth. A hydrosoluble extract (hazelnut shell extract, HSE) was prepared by the maceration method using a hydroalcoholic solution and used as the active ingredient of patches (prepared by casting method) consisting of composites of highly deacetylated chitosan and green clay. In vitro studies showed that the formulation containing HSE is able to stimulate keratinocyte growth, which is useful for healing purposes, and to inhibit the growth of S. aureus (Log CFU/mL 0.95 vs. 8.85 of the control after 48 h); this bacterium is often responsible for wound infections and is difficult to treat by conventional antibiotics due to its antibiotic resistance. The produced patches showed suitable tensile properties that are necessary to withstand mechanical stress during both the removal from the packaging and application. The obtained results suggest that the developed patch could be a suitable product to treat wounds.

Formulation and characterization of sustainable bioadhesive films for wound treatment based on barley ß-glucan extract obtained using the high power ultrasonic technique.

ß-glucan is a well-known functional and bioactive food ingredient. Recently, some studies highlighted several interesting pharmacological activities, such as hypocholesterolemic, hypoglycemic, immunomodulatory, antitumor, antioxidant and anti-inflammatory. The aim of this study is to evaluate a novel application of ß-glucan, obtained from barley, for the development of formulations for skin use. Several water suspensions were obtained from barley flour of different particle sizes treated by high power ultrasonic (HPU) technique. Barley flour fraction in the range of 400-500 µm allowed to obtain a stable suspension, represented both by a water soluble and water insoluble fraction of ß-glucans, that showed excellent film forming ability. The plasticizer sorbitol as well as the bioadhesive biopolymer acacia gum were added to this suspension in order to obtain a gel suitable to prepare films by casting. The obtained films demonstrated suitable mechanical properties and ability to stimulate in vitro keratinocytes growth suggesting its possible application in dermatological field as for wound treatment. This study demonstrated the dual use of barley suspension: as excipient and as active ingredient.

Recent Approaches for Wound Treatment.

Wounds are a serious global health problem [...].

Effect of Different Drying Treatments and Sieving on Royal Gala Apple Pomace, a Thickening Agent with Antioxidant Properties.

Currently, there is an increasing interest in the search of natural derived materials as valuable substitutes for microplastics. One of the categories investigated, represented by thickening agents deriving from agri-food waste and apple pomace (AP), was considered of interest. In this study AP was submitted to three different treatments and drying conditions (oven drying at 55 °C for 12 h; homogenization and oven drying at 55 °C for 12 h; homogenization and freeze-drying), and then grinded and sieved obtaining three different dimensional fractions (>400 µm, 250-400 µm and <250 µm). The hydroalcoholic extracts of these fractions, obtained by ultrasound-assisted extraction, were analyzed to compare their total phenol content (TPC), antioxidant properties, and phenol profile. Correlation studies between the above-indicated parameters were also carried out. The highest values of TPC, antioxidant capacity, and phenol content (determined by liquid chromatography) were found for oven dried AP (250-400 µm) or homogenized and freeze-dried (>400 µm) samples. Both samples were most suitable to form stable hydrogels and the sample obtained after drying at 55 °C showed the best performances in terms of ability to form a stable hydrogel. Among the studied treatments and drying conditions, the oven dried AP was demonstrated to be an interesting stabilizing material with potential applications in many fields (such as food, cosmetics, and nutraceuticals) showing both antioxidant activity and thickening capacity.

Starch-based sustainable hydrogel loaded with Crocus sativus petals extract: A new product for wound care.

The aim of the present study was to valorize Crocus sativus petals, the main waste deriving from saffron stigma harvesting, as source of bioactive molecules to be used in health field. Three different dry extracts were prepared by eco-friendly methods (maceration and ultrasound bath assisted maceration) using saffron petals as raw material and ethanol 70 % either ethanol 96 % as extraction solvents. A preliminary evaluation of the antioxidant activity (measured by ABTS*+, DPPH* and FRAP) highlighted that the most suitable extraction solvent is represented by ethanol 70 %. By in vitro studies on keratinocytes emerged that the extract obtained by maceration (rich in gallic and chlorogenic acids) stimulates their growth in a safe concentration range (0.02-0.4 mg/mL) suggesting a potential application in skin diseases such as superficial wounds. Due to the low manageability, the extract was firstly supported on corn starch powder particles and then formulated as starch gel. The obtained formulation showed both suitable rheological properties and spreadability necessary for an easy and pain free application on damaged skin. Moreover, in vitro microbiological studies of starch gel demonstrated antimicrobial activity toward S. epidermidis and self-preserving capacity.

MgAl and ZnAl-Hydrotalcites as Materials for Cosmetic and Pharmaceutical Formulations: Study of Their Cytotoxicity on Different Cell Lines.

The knowledge about the effect of hydrotalcites (HTlcs), largely used in pharmaceutics, on non-malignant cell lines is limited. The effect of MgAl-HTlc-and ZnAl-HTlc- (NO3−/Cl−/CO32−) on the cell viability of HaCat, fibroblasts and HepG2 was studied by MTT assay. Cells were incubated either with HTlc suspensions in the culture media and with the supernatant obtained from the suspension being centrifuged. MgAl-HTlcs suspensions resulted in being cytotoxic. As SEM and TEM analyses showed the presence of sub-micrometric particles in all the MgAl-HTlc examined, it could be hypothesized that this fraction can be internalized into cells reducing the viability. MgAl-HTlc-NO3 is the most cytotoxic probably due to the additional effect of NO3− anions. ZnAl-HTlcs are cytotoxic, especially for HaCat and HepG2 cells (viability <60% at all the concentrations assayed). The effect is attributable both to the sub-micrometric fraction (identified by TEM) and to the high Zn2+ levels found in the culture medium by ICP-OES analysis, suggesting that ZnAl-HTlcs are less stable than MgAl-HTlc in the used media. The obtained results suggest that it is very important to perform ad hoc studies in order to evaluate HTlc safety before to be introduced in a formulation.

Crocus sativus L. Petal Extract Inhibits Inflammation and Osteoclastogenesis in RAW 264.7 Cell Model.

The dried stigmas of Crocus sativus L. (Iridaceae) are traditionally processed to produce saffron, a spice widely used as a food coloring and flavoring agent, which is important in the pharmaceutical and textile dye-producing industries. The labor-intensive by-hand harvesting and the use of only a small amount of each flower cause saffron to be the most expensive spice in the world. Crocus sp. petals are by-products of saffron production and represent an interesting raw material for the preparation of extracts intended for health protection in the perspective of a circular economy. In the present study, ethanolic extract from Crocus sativus L. petals (Crocus sativus L. petal extract, CsPE) was tested on macrophages by in vitro models of inflammation and osteoclastogenesis. The extract was found to be endowed with anti-inflammatory activity, significantly reducing the nitric oxide production and IL-6 release by RAW 264.7 murine cells. Moreover, CsPE demonstrated an anti-osteoclastogenic effect, as revealed by a complete inhibition of tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and a decreased expression of key osteoclast-related genes. This study, which focuses on the macrophage as the target cell of the bioactive extract from Crocus sativus L. petals, suggests that the petal by-product of saffron processing can usefully be part of a circular economy network aimed at producing an extract that potentially prevents bone disruption.

Wound Dressing: Combination of Acacia Gum/PVP/Cyclic Dextrin in Bioadhesive Patches Loaded with Grape Seed Extract.

The success of wound treatment is conditioned by the combination of both suitable active ingredients and formulation. Grape seed extract (GSE), a waste by-product obtained by grape processing, is a natural source rich in many phenolic compounds responsible for antioxidant, anti-inflammatory, and antimicrobial activities and for this reason useful to be used in a wound care product. Bioadhesive polymeric patches have been realized by combining acacia gum (AG) and polyvinylpyrrolidone (PVP). Prototypes were prepared by considering different AG/PVP ratios and the most suitable in terms of mechanical and bioadhesion properties resulted in the 9.5/1.0 ratio. This patch was loaded with GSE combined with cyclic dextrin (CD) to obtain the molecular dispersion of the active ingredient in the dried formulation. The loaded patch resulted mechanically resistant and able to release GSE by a sustained mechanism reaching concentrations able to stimulate keratinocytes' growth, to exert both antibacterial and antioxidant activities.

Antibacterial Activity of Crocus sativus L. Petals Extracts against Foodborne Pathogenic and Spoilage Microorganisms, with a Special Focus on Clostridia.

In recent years, there has been a growing interest in the use of novel antimicrobial agents able to inhibit or kill food-borne bacteria or to interrupt the onset of food spoilage. Crocus sativus L. petals, typically considered as waste obtained from saffron spice production, could be a source of natural bioactive compounds to be used as food preservatives. The purpose of this work was to investigate the antibacterial properties of two hydroalcoholicsaffron petal extracts obtained by maceration (SPEA) and by ultrasonic bath (SPEB) methods. The main polyphenols identified in both extracts were gallic and chlorogenic acids, representing almost 70% of the phenolic fraction monitored. The antibacterial activity was studied by the agar well-diffusion method, against food-borne pathogenic and spoilage bacteria. Both extracts showed activity mainly against Gram-positive bacteria, in particular those belonging to the Clostridiaceae family (C. perfringens, C. botulinum and C. difficile), with inhibition zone diameters ranging from 13 to 18 mm. The antibacterial properties against Clostridia were further analyzed, determining MIC and MBC and performing a time-kill test. SPEA showed lower MIC/MBC values (250 mg/mL) compared to SPEB (500 mg/mL), suggesting that it could be more active against the assayed strains, probably because of its higher content of gallic acid. SPEA and SPEB, tested at a concentration of 1 × MIC, showed bactericidal activity against C. perfringens, C. botulinum and C. difficile and these results suggest that saffron petals could represent a valuable natural alternative source to conventional preservatives. Further investigations are needed to evaluate possible applications in the food industry.

Hazelnut Shells as Source of Active Ingredients: Extracts Preparation and Characterization.

Hazelnut shells represent a waste material (about 42% of the total biomass) deriving from hazelnut harvest. These are mainly used as a heating source; however, they represent an interesting source of polyphenols useful in health field. The impact on phenolic profile and concentrations of hazelnut shell extracts obtained by three extraction methods (maceration, ultrasonic bath, and high-power ultrasonic), as well as temperature, extraction time, and preventive maceration, was studied. The prepared extracts were characterized in terms of chemical composition, antioxidant and antimicrobial activities. Eighteen different phenolic compounds were identified and quantified by chemical analysis and gallic acid was the most abundant in all the extracts analyzed. Other relevant compounds were chlorogenic acid, protocatechuic acid and catechin. Preventive maceration had a positive effect on the extraction of different types of compounds regardless of the method performed. Application of the high-power ultrasonic method had different effects, either positive or negative, depending on the type of compound and extraction time. All the prepared extracts showed antioxidant activity especially those prepared by maceration, and many of them were able to inhibit the growth of both B. subtilis and B. cereus.

Emulgel Loaded with Flaxseed Extracts as New Therapeutic Approach in Wound Treatment.

Dry (D.E.) and liquid (L.E.) extracts were prepared from flaxseeds and their application in health field was evaluated. The chemical analysis showed that D.E. is rich in the lignan secoisolariciresinol diglucoside and L.E. in unsaturated triglycerides containing linolenic acid. Mainly, D.E. showed reducing (15.73 µmol Fe2+/g) and radical scavenging capacities (5.25 mg TE/g) and ability to down-regulate the expression of the pro-inflammatory cytokines NO (IC50 = 0.136 ± 0.009 mg/mL) and IL-6 (IC50 = 0.308 ± 0.103 mg/mL), suggesting its use in wound treatment. D.E. and L.E. were active against S. pyogenes and D.E. also against S. aureus. The two extracts were combined in a novel O/W emulgel in which the water phase was viscosized using a low molecular weight and highly deacetylated chitosan (1% wt./v). The presence of this polymer in the emulgel decreased the MIC values of the extracts. In fact, MIC shifted from 0.59 mg/mL to 0.052 mg/mL for D.E. and from 0.22 mg/mL to 0.036 mg/mL for L.E., concentrations safe both for keratinocytes and macrophages. Moreover, the emulgel demonstrated to inhibit S. aureus, P. aeruginosa, S. pyogenes, E. coli, and K. pneumoniae growth (inhibition halos 24-36 mm), strains often responsible for diabetic foot ulcer infection.

Development of sodium carboxymethyl cellulose based polymeric microparticles for in situ hydrogel wound dressing formation.

18ß-glycyrrhetinic acid (Gly), a natural compound obtained from licorice, is known both for the anti-inflammatory and antioxidant activities and for this reason useful for wound treatment. Due to its poor solubility, Gly is not suitable for formulations used in conventional topical products such as gels, foams and creams. Polymeric bioadhesive microparticles (MP), loaded with Gly, were developed to be introduced in the wound bed and swell, once in contact with the exudate, to form a hydrogel in situ able to close the wound. The MP were prepared by spray drying method from the polymeric solution of polysaccharide sodium carboxymethyl cellulose (CMC) and copolymer Soluplus® (SL). Soluplus® introduction in MP composition, using a 3:1 ratio (CMC/SL wt./wt.), allowed to stabilize Gly in non-crystalline form, favoring the improvement of water solubility, and to obtain a spherical with rugged surface MP morphology. Ex vivo studies showed these MP maintain high swelling capability and are able to form in situ a hydrogel for wound repair. The controlled release of Gly from the hydrogel stimulates keratinocyte growth, potentially supporting the physiological healing processes.

Development and Characterization of Xanthan Gum and Alginate Based Bioadhesive Film for Pycnogenol Topical Use in Wound Treatment.

Pycnogenol (PYC) is a concentrate of phenolic compounds derived from French maritime pine; its biological activity as antioxidant, anti-inflammatory and antibacterial suggests its use in the treatment of open wounds. A bioadhesive film, loaded with PYC, was prepared by casting, starting with a combination of two biopolymer acqueous solutions: xanthan gum (1% wt/wt) and sodium alginate (1.5% wt/wt), in a 2.5/7.5 (wt/wt) ratio. In both solutions, glycerol (10% wt/wt) was added as plasticizing agent. The film resulted in an adhesive capable to absorb a simulated wound fluid (~ 65% wt/wt within 1 h), therefore suitable for exuding wounds. The mechanical characterization showed that the film is deformable (elastic modulus E = 3.070 ± 0.044 MPa), suggesting adaptability to any type of surface and resistance to mechanical solicitations. PYC is released within 24 h by a sustained mechanism, achieving a maximum concentration of ~ 0.2 mg/mL, that is safe for keratinocytes, as shown by cytotoxicity studies. A concentration of 0.015 mg/mL is reached in the first 5 min after application, at which point PYC stimulates keratinocyte growth. These preliminary results suggest the use of PYC in formulations designed for topical use.

Polymeric Bioadhesive Patch Based on Ketoprofen-Hydrotalcite Hybrid for Local Treatments.

Ketoprofen (KET) represents one of the most common drugs used in the topical treatment of pain and inflammations. However, its potential is rather limited due to the very low solubility and photochemical instability. The local administration of KET by conventional products, such as gels, emulgels, creams, and foams, does not guarantee an efficacious and safe treatment because of its low absorption (due to low solubility) and its sensitivity to UV rays. The photodegradation of KET makes many photoproducts responsible for different adverse effects. In the present work, KET was intercalated into the lamellar anionic clay ZnAl-hydrotalcite (ZnAl-HTlc), obtaining the hybrid ZnAl-KET with improved stability to UV rays and water solubility in comparison to the crystalline form (not intercalated KET). The hybrid was then formulated in autoadhesive patches for local pain treatment. The patches were prepared by casting method starting from a hydrogel based on the biocompatible and bioadhesive polymer NaCMC (Sodium carboxymethycellulose) and glycerol as a plasticizing agent. The introduction of ZnAl-KET in the patch composition demonstrated the improvement in the mechanical properties of the formulation. Moreover, a sustained and complete KET release was obtained within 8 h. This allowed reducing the frequency of anti-inflammatory administration, compared to the conventional formulations.

Preparation and characterization of polymeric microparticles loaded with Moringa oleifera leaf extract for exuding wound treatment.

The aim of this study was to develop an innovative formulation, particularly useful for the treatment of exuding wounds. An extract from Moringa oleifera leaves (MOE), prepared by an eco-friendly method, was used as active ingredient. Its preliminary characterization showed that MOE is rich in quercetin-O-glucoside and quercetin-O-malonyl glucoside, responsible for the antioxidant, radical scavenging and antibacterial activities (toward Staphylococcus aureus, S. epidermidis, S. faecalis and S. pyogenes). Moreover, MOE showed the ability to stimulate keratinocytes growth. Thus, bioadhesive biocompatible polymeric microparticles loaded with such extract were developed and prepared in order to treat exuding wounds. The microparticles, obtained by spray drying, using chitosan as polymer, showed good swelling ability. This is useful to obtain the transition from microparticles to a continuous gel covering the wound, after deposition on it. This has the double function to protect the damage area and to promote the healing. The in vitro release study showed that the formed gel is able to release immediately MOE, in the first minutes after application, and to promote a sustained release within 24 h reaching an efficacious concentration against the most sensitive bacterial strains. These findings suggest that the developed microparticles represent an interesting tool for exuding wounds treatment.

[Dermo-cosmetic control of cutaneous adverse effects in the oncological patient.] / Il controllo dermo-cosmetologico dei sintomi cutanei nel malato oncologico.

Cutaneous adverse effects are often associated to cancer therapies. Modifications of the aspect represent one of the factors responsible for quality of life decrese, particularly visible in women. It must be underlined also that in many female tumors the cutaneous adverse effects are often enhanced by the hormonal levels inducing skin damage and photoinduced reactions. In this scenario the cosmetic oncology plays a very important role. In fact, it is a branch of cosmetic, having high social and ethical value born to support oncological patients by physical appearance improvement. The skin and cutaneous annexes of the oncological patient are different in comparison to that of health people requiring particular attention. In first instance a high skin protection and hydration is necessary for such patients. For this reason, the cosmetic oncology supports the oncological patients in the improvement of their appearance by means of specific products and skin care procedures. Projects of cosmetic oncology, involving many territorial pharmacies, raised with the idea that the attenuation of the external signs therapy-induced can contribute to the improvement of the patient quality of life.

Bioadhesive Polymeric Films Based on Red Onion Skins Extract for Wound Treatment: An Innovative and Eco-Friendly Formulation.

The onion non-edible outside layers represent a widely available waste material deriving from its processing and consumption. As onion is a vegetable showing many beneficial properties for human health, a study aiming to evaluate the use of extract deriving from the non-edible outside layers was planned. An eco-friendly extraction method was optimized using a hydroalcoholic solution as solvent. The obtained extract was deeply characterized by in vitro methods and then formulated in autoadhesive, biocompatible and pain-free hydrogel polymeric films. The extract, very soluble in water, showed antioxidant, radical scavenging, antibacterial and anti-inflammatory activities, suggesting a potential dermal application for wounds treatment. In vitro studies showed a sustained release of the extract from the hydrogel polymeric film suitable to reach concentrations necessary for both antibacterial and anti-inflammatory activities. Test performed on human keratinocytes showed that the formulation is safe suggesting that the projected formulation could be a valuable tool for wound treatment.

Development and characterization of mucoadhesive-thermoresponsive gels for the treatment of oral mucosa diseases.

INTRODUCTION: The mucositis is an inflammatory, erosive and ulcerative process of the oral mucosa. It is usually caused by radiation, chemotherapy, infections, diabetes, smoking and it is characterized by severe pain and difficulty eating and can have a very serious impact on quality of life. A suitable treatment must ensure pain control and mechanical protection to promote mucosal healing. The purpose of this work was to study an in-situ gelling formulation to be sprayed onto the damaged oral mucosa by self-administration. The formulation must be able to quickly form a film when applied in the oral cavity. METHODS: many batches were prepared mixing a thermosensitive polymer (poloxamer PF127 or P123) with mucoadhesive polymers polyvinylpyrrolidone (PVP), sodium carboxymethyl cellulose (NaCMC), Carbopol 971P, chitosan (CS). By an experimental design three suitable formulations were identified and loaded with the model drug benzydamine hydrochloride. The hydrogel based on 25.50% PF127, 0.20% PVP and 0.35% CS maintained its original properties (gelling, rheological and mucoadhesive) after loading and showing a sustained drug release. CONCLUSIONS: the selected hydrogel showed to be suitable for the treatment of mucositis, able to reduce the number of daily administration and to protect the damaged mucosa from mechanical and chemical solicitations.