Hollow Particles Obtained by Prilling and Supercritical Drying as a Potential Conformable Dressing for Chronic Wounds.

The production of aerogels for different applications has been widely known, but the use of polysaccharide-based aerogels for pharmaceutical applications, specifically as drug carriers for wound healing, is being recently explored. The main focus of this work is the production and characterization of drug-loaded aerogel capsules through prilling in tandem with supercritical extraction. In particular, drug-loaded particles were produced by a recently developed inverse gelation method through prilling in a coaxial configuration. Particles were loaded with ketoprofen lysinate, which was used as a model drug. The core-shell particles manufactured by prilling were subjected to a supercritical drying process with CO2 that led to capsules formed by a wide hollow cavity and a tunable thin aerogel layer (40 µm) made of alginate, which presented good textural properties in terms of porosity (89.9% and 95.3%) and a surface area up to 417.0 m2/g. Such properties allowed the hollow aerogel particles to absorb a high amount of wound fluid moving very quickly (less than 30 s) into a conformable hydrogel in the wound cavity, prolonging drug release (till 72 h) due to the in situ formed hydrogel that acted as a barrier to drug diffusion.

Flogomicina: A Natural Antioxidant Mixture as an Alternative Strategy to Reduce Biofilm Formation.

The National Institute of Health has reported that approximately 80% of chronic infections are associated with biofilms, which are indicated as one of the main reasons for bacteria's resistance to antimicrobial agents. Several studies have revealed the role of N-acetylcysteine (NAC), in reducing biofilm formation induced by different microorganisms. A novel mixture made up of NAC and different natural ingredients (bromelain, ascorbic acid, Ribes nigrum, resveratrol, and pelargonium) has been developed in order to obtain a pool of antioxidants as an alternative strategy for biofilm reduction. The study has demonstrated that the mixture is able to significantly enhance NAC activity against different Gram-positive and Gram-negative bacteria. It has shown an increase in NAC permeation in vitro through an artificial fluid, moving from 2.5 to 8 µg/cm2 after 30 min and from 4.4 to 21.6 µg/cm2 after 180 min, and exhibiting a strongly fibrinolytic activity compared to the single components of the mixture. Moreover, this novel mixture has exhibited an antibiofilm activity against S aureus and the ability to reduce S. aureus growth by more than 20% in a time-killing assay, while on E. coli, and P. mirabilis, the growth was reduced by more than 80% compared to NAC. The flogomicina mixture has also been proven capable of reducing bacterial adhesion to abiotic surfaces of E.coli, by more than 11% concerning only the NAC. In combination with amoxicillin, it has been shown to significantly increase the drug's effectiveness after 14 days, offering a safe and natural way to reduce the daily dosage of antibiotics in prolonged therapies and consequently, reduce antibiotic resistance.

Alginate-pectin microparticles loaded with nanoemulsions as nanocomposites for wound healing.

This work combines natural polymers with nanoemulsions (NEs) to formulate nanocomposites as an innovative wound dressing. Spray-drying has been used to produce alginate-pectin in situ gelling powders as carriers for NEs loaded with curcumin (CCM), a model antimicrobial drug. The influence of NEs encapsulation in polymer-based microparticles was studied in terms of particle size distribution, morphology, and stability after spray-drying. NEs loading did not affect the size of microparticles which was around 3.5 µm, while the shape and surface morphology analyzed using scanning electron microscope (SEM) changed from irregular to spherical. Nanocomposites as dried powders were able to form a gel in less than 5 min when in contact with simulated wound fluid (SWF), while the value of moisture transmission of the in situ formed hydrogels allowed to promote good wound transpiration. Moreover, rheologic analyses showed that in situ formed gels loaded with NEs appeared more elastic than blank formulations. The in situ formed gel allowed the prolonged release of CCM-loaded NEs in the wound bed, reaching 100% in 24 h. Finally, powders cytocompatibility was confirmed by incubation with keratinocyte cells (HaCaT), proving that such nanocomposites can be considered a potential candidate for wound dressings.

In Situ Hydrogel Formulation for Advanced Wound Dressing: Influence of Co-Solvents and Functional Excipient on Tailored Alginate-Pectin-Chitosan Blend Gelation Kinetics, Adhesiveness, and Performance.

Chronic skin wounds affect more than 40 million patients worldwide, representing a huge problem for healthcare systems. This study elucidates the optimization of an in situ gelling polymer blend powder for biomedical applications through the use of co-solvents and functional excipients, underlining the possibility of tailoring microparticulate powder properties to generate, in situ, hydrogels with advanced properties that are able to improve wound management and patient well-being. The blend was composed of alginate, pectin, and chitosan (APC). Various co-solvents (ethanol, isopropanol, and acetone), and salt excipients (sodium bicarbonate and ammonium carbonate) were used to modulate the gelation kinetics, rheology, adhesiveness, and water vapor transmission rate of the gels. The use of co-solvents significantly influenced particle size (mean diameter ranging from 2.91 to 5.05 µm), depending on the solvent removal rate. Hydrogels obtained using ethanol were able to absorb over 15 times their weight in simulated wound fluid within just 5 min, whereas when sodium bicarbonate was used, complete gelation was achieved in less than 30 s. Such improvement was related to the internal microporous network typical of the particle matrix obtained with the use of co-solvents, whereas sodium bicarbonate was able to promote the formation of allowed particles. Specific formulations demonstrated an optimal water vapor transmission rate, enhanced viscoelastic properties, gel stiffness, and adhesiveness (7.7 to 9.9 kPa), facilitating an atraumatic removal post-use with minimized risk of unintended removal. Microscopic analysis unveiled that porous inner structures were influencing fluid uptake, gel formation, and transpiration. In summary, this study provided valuable insights for optimizing tailored APC hydrogels as advanced wound dressings for chronic wounds, including vascular ulcers, pressure ulcers, and partial and full-thickness wounds, characterized by a high production of exudate.

Recapsoma®: A Novel Mixture Based on Bergamot, Ipomoea Batatas, Policosanol Extracts and Liposomal Berberine for the Treatment of Hypercholesterolemia.

Cardiovascular disease (CVD) is considered one of the major causes of mortality worldwide. Epidemiological studies have shown that regular consumption of phenols is inversely associated with cardiovascular disease, and the use of nutraceuticals and functional foods can provide protective, preventive, and possibly curative effects in CVD. A novel mixture of different natural substances named Recapsoma® (bergamot, liposomal berberine, Ipomoea batatas, oleuropein, polycosanols, and vitamin E) has been produced, and its anti-dyslipidaemic efficacy has been tested, specifically studying the in vitro effects on the mechanisms of action underlying cholesterol synthesis, triglycerides, and LDL-cholesterol oxidation. The work has demonstrated the ability of this herbal extract mixture to inhibit the action of PCSK, ACAT, PAP, and HMGR and to increase the LDL receptor (LDLR), underlying the synergistic effect of the mixture over the single components. Such results suggest that the Recapsoma® mixture could be used as a tool for controlling hypercholesterolemia, and an alternative to statins, especially for those patients with metabolic syndrome.

Supercritical Antisolvent Technique for the Production of Breathable Naringin Powder.

Flavonoids are polyphenolic compounds largely present in fruits and vegetables possessing antioxidant properties, anti-inflammatory and antibacterial activities. Their use in clinical practice is very poor due to their low bioavailability, susceptibility to oxidation and degradation. Moreover, their slight solubility in biological fluids and a consequent low dissolution rate leads to an irregular absorption from solid dosage forms, even though, anti-inflammatory formulations could be used as support for several disease treatment, i.e. the COVID-19 syndrome. To improve flavonoid bioavailability particle size of the powder can be reduced to make it breathable and to promote the absorption in the lung tissues. Supercritical fluid based antisolvent technique has been used to produce naringin particles, with size, shape and density as well as free flowing properties able to fit inhalation needs. The dried particles are produced with the removal of the solvent at lower temperatures compared to the most used traditional micronization processes, such as spray drying. The best breathable fraction for naringin particles is obtained for particles with a d50~7 µm manufactured at 35 °C-150 bar and at 60 °C-130 bar, corresponding to 32.6% and 36.7% respectively. The powder is produced using a high CO2 molar fraction (0.99) that assure a better removal of the solvent. NuLi-1 cell line of immortalised bronchial epithelial cells adopted to evaluate powder cytotoxicity indicated after 24 h absence of toxicity at concentration of 25 µM.

A Novel Three-Polysaccharide Blend In Situ Gelling Powder for Wound Healing Applications.

In this paper, alginate/pectin and alginate/pectin/chitosan blend particles, in the form of an in situ forming hydrogel, intended for wound repair applications, have been successfully developed. Particles have been used to encapsulate doxycycline in order to control the delivery of the drug, enhance its antimicrobial properties, and the ability to inhibit host matrix metalloproteinases. The presence of chitosan in the particles strongly influenced their size, morphology, and fluid uptake properties, as well as drug encapsulation efficiency and release, due to both chemical interactions between the polymers in the blend and interactions with the drug demonstrated by FTIR studies. In vitro antimicrobial studies highlighted an increase in antibacterial activity related to the chitosan amount in the powders. Moreover, in situ gelling powders are able to induce a higher release of IL-8 from the human keratinocytes that could stimulate the wound healing process in difficult-healing. Interestingly, doxycycline-loaded particles are able to increase drug activity against MMPs, with good activity against MMP-9 even at 0.5 µg/mL over 72 h. Such results suggest that such powders rich in chitosan could be a promising dressing for exudating wounds.

In situ gelling alginate-pectin blend particles loaded with Ac2-26: A new weapon to improve wound care armamentarium.

In this paper, alginate-pectin blend particles loaded with Annexin A1 derived peptide Ac2-26 as an in situ forming dressing was successfully developed for wound repair applications. High mannuronic (M) content alginate and amidated pectin blend have been used to encapsulate Ac2-26 in order to enhance stability of the peptide at room temperature and to control its release through the in situ formed gel. Ac2-26 recovery and FTIR studies suggests chemical interactions between peptide and polysaccharides blend able to improve the encapsulation efficiency of Ac2-26 into the polymer matrix and control its release, till 48 h. In vitro wound healing assay on HaCaT cells highlights the ability of Ac2-26 to significantly accelerate wound healing compared to unloaded particles, with complete closure of the wound model in 24 h. Therefore, all these results suggest that Ac2-26 loaded submicrometric in situ gelling powders could be a promising wound dressing to improve wound care armamentarium.