Smart nano-in-microparticles to tackle bacterial infections in skin tissue engineering

Chronic wounds (resulting from underlying disease, metabolic disorders, infections, trauma, and even tumours) pose significant health problems. In this work, microparticles, based on polysaccharides (maltodextrin or dextran) and amino acids, and doped with antibacterial nanoparticles (CuO or ZnO NPs) are designed. Smart nano-inmicroparticles with a hierarchical 3D structure are developed. The ultimate goal aims at an innovative platform to achieve skin repair and to manage skin colonization by avoiding infection that could delay and even impair the healing process. The microparticles are prepared by spray-drying and cross-linked by heating, to obtain insoluble scaffolds able to facilitate cell proliferation in the wound bed. The nano-in-microparticles are characterized using a multidisciplinary approach: chemico–physical properties (SEM, SEM-EDX, size distribution, swelling and degradation properties, structural characterization - FTIR, XRPD, SAXS – mechanical properties, surface zeta potential) and preclinical properties (in vitro biocompatibility and whole-blood clotting properties, release studies and antimicrobial properties, and in vivo safety and efficacy on murine burn/excisional wound model) were assessed. The hierarchical 3D nano-in microparticles demonstrate to promote skin tissue repair in a preclinical study, indicating that this platform deserves particular attention and further investigation will promote the prototypes translation to clinics.Horizon 2020 Research and Innovation Programme 814607National Science Foundation (NSF) DMR-0520547EC Horizon 2020 program under the SINE2020 projectESRF 65400

Bentonite- and Palygorskite-Based Gels for Topical Drug Delivery Applications

The project was funded by P18-RT-3786 project of Junta de Andalucia (Spain). This research was partially supported by UniCA-Progetti biennali di Ateneo Finanziati dalla Fondazione di Sardegna 2018 (CUP F741I19000950007)Bentonite or palygorskite-based hydrogels have recently been suggested as a strategy to increase bioavailability and control the retention and release of therapeutic candidates. In this work, clay-based hydrogels loaded with diclofenac acid nanocrystals have been successfully designed and developed. The aim was to improve diclofenac solubility, its dissolution rate and to enhance its local bioavailability after topical application. For this purpose, diclofenac acid nanocrystals were prepared by wet media milling technology and then loaded into inorganic hydrogels based on bentonite and/or palygorskite. Diclofenac acid nanocrystals were characterized by morphology, size, and zeta potential. Moreover, rheological behavior, morphology, solid state, release studies, and in vitro skin penetration/permeation of diclofenac acid nanocrystals-loaded hydrogels were performed. The hydrogels were characterized by a crystalline structure, and demonstrated that the inclusion of diclofenac in clay-based hydrogels resulted in an increased thermal stability. The presence of both palygorskite and bentonite reduced nanocrystal mobility, and consequently its release and penetration into the skin. On the other hand, bentonite- or palygorskite-based hydrogels revealed great potential as an alternative strategy to enhance topical bioavailability of DCF nanocrystals, enhancing their penetration to the deeper skin layers.Junta de Andalucia P18-RT-3786UniCA-Progetti biennali di Ateneo Finanziati dalla Fondazione di Sardegna 2018 CUP F741I1900095000

Wound Healing Activity of Nanoclay/Spring Water Hydrogels

This project was supported by an FPU grant (MECD), the Spanish research group CTS-946 and the program for international mobility of PhD students (University of Granada). Special thanks to the Department of Drug Sciences of the University of Pavia (Italy).Background: hydrogels prepared with natural inorganic excipients and spring waters are commonly used in medical hydrology. Design of these clay-based formulations continues to be a field scarcely addressed. Safety and wound healing properties of different fibrous nanoclay/spring water hydrogels were addressed. Methods: in vitro biocompatibility, by means of MTT assay, and wound healing properties were studied. Confocal Laser Scanning Microscopy was used to study the morphology of fibroblasts during the wound healing process. Results: all the ingredients demonstrated to be biocompatible towards fibroblasts. Particularly, the formulation of nanoclays as hydrogels improved biocompatibility with respect to powder samples at the same concentration. Spring waters and hydrogels were even able to promote in vitro fibroblasts motility and, therefore, accelerate wound healing with respect to the control. Conclusion: fibrous nanoclay/spring water hydrogels proved to be skin-biocompatible and to possess a high potential as wound healing formulations. Moreover, these results open new prospects for these ingredients to be used in new therapeutic or cosmetic formulations.German Research Foundation (DFG)Spanish research group CTS-946Program for international mobility of PhD students (University of Granada

Praziquantel–Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained.Ministerio de Ciencia e Innovacion government PCIN-2017-098 FIS2016-77692-C2-2-P CGL2016-80833-RJunta de Andalucia RNM1897 P18-RT-378

Clay-Based Hydrogels as Drug Delivery Vehicles of Curcumin Nanocrystals for Topical Application

The poor water solubility of a significant number of active pharmaceutical ingredients (API) remains one of the main challenges in the drug development process, causing low bioavailability and therapeutic failure of drug candidates. Curcumin is a well-known Biopharmaceutics Classification System (BCS) class IV drug, characterized by lipophilicity and low permeability, which hampers topical bioavailability. Given these premises, the aim of this work was the design and the development of curcumin nanocrystals and their incorporation into natural inorganic hydrogels for topical application. Curcumin nanocrystals were manufactured by the wet ball milling technique and then loaded in clay-based hydrogels. Bentonite and/or palygorskite were selected as the inorganic gelling agents. Curcumin nanocrystal-loaded hydrogels were manufactured by means of a homogenization process and characterized with respect to their chemico-physical properties, in vitro release, antioxidant activity and skin permeation. The results highlighted that the presence of bentonite provided an increase of curcumin skin penetration and simultaneously allowed its radical scavenging properties, due to the desirable rheological characteristics, which should guarantee the necessary contact time of the gel with the skin.UniCA-Progetti biennali di Ateneo Finanziati dalla Fondazione di Sardegna 2018 (CUP F741I19000950007)P18-RT-3786 project of Junta de Andalucia (Spain

Antioxidant Efficacy and “In Vivo” Safety of a Bentonite/Vitamin C Hybrid

The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/pharmaceutics15041171/s1, S1: LAA/smectites systems: critical revision; S2: Ophthalmic irritability; S3: Acute dermal toxicity.L-ascorbic acid (LAA), commonly known as vitamin C, is an excellent and recognized antioxidant molecule used in pharmaceutical and cosmetic formulations. Several strategies have been developed in order to preserve its chemical stability, connected with its antioxidant power, but there is little research regarding the employment of natural clays as LAA host. A safe bentonite (Bent)—which was verified by in vivo ophthalmic irritability and acute dermal toxicity assays—was used as carrier of LAA. The supramolecular complex between LAA and clay may constitute an excellent alternative, since the molecule integrity does not seem to be affected, at least from the point of view of its antioxidant capacity. The Bent/LAA hybrid was prepared and characterized through ultraviolet (UV) spectroscopy, X-ray diffraction (XRD), infrared (IR) spectroscopy, thermogravimetric analysis (TG/DTG) and zeta potential measurements. Photostability and antioxidant capacity tests were also performed. The LAA incorporation into Bent clay was demonstrated, as well as the drug stability due to the Bent photoprotective effect onto the LAA molecule. Moreover, the antioxidant capacity of the drug in the Bent/LAA composite was confirmed.France Embassy in CubaErasmus+ scholarshipTWAS 00-360 RG/CHE/LA, 07-016 RG/CHE/LAPN211LH008-027, PN223LH010-01

Hybrid Lipid/Clay Carrier Systems Containing Annatto Oil for Topical Formulations

Financial support for this research was provided by the Coordination of Improvement of Higher-Level Personnel-Brazil (CAPES)-02817/09. RMB and FNR acknowledge fellowships from National Council for Scientific and Technological Development CNPq (Brazil). This research also was financially supported by Junta de Andalucia, under the project reference PT18 RT 3786.Nanocomposites formed by clay and lipid carriers (NLCs) show a high potential for providing controlled release and specific delivery of bioactive molecules and have recently gained attention in the pharmaceutical sector due to their ability to transport hydrophilic and hydrophobic drugs. Recent studies have recognized the biological activity of the oil of Bixa orellana L. (AO) with regards to its healing, antioxidant, antibacterial, and anti-leishmanial properties. Therefore, the purpose of this study is the preparation and characterization of hybrid systems based on lipid nanocarriers and laponite for the delivery of AO. NLCs were prepared by the fusion-emulsification method, using cetyl palmitate (CP) or myristyl myristate (MM), AO, and Poloxamer 188. The morphology, hydrodynamic diameters, zeta potential (ZP), polydispersity index (PDI), thermal analysis, X-ray diffraction analysis (XRD), viscosity behavior, and cytotoxicity testing of the hybrid systems were performed. The thermal study and X-ray diffraction analyses (XRD) revealed polymorphic structural changes compatible with the amorphization of the material. Rheological assays highlighted a typical pseudoplastic behavior in all systems (MM and CP with LAP). The hybrid systems’ morphology, size diameters, and PDIs were similar, preset spherical and monodisperse structures ( 200 nm; <0.3), without significant change up to sixty days. The ZP values differed from each other, becoming higher with increasing AO concentration. XEDS spectra and elemental X-ray maps show peaks of lipids (organic components, C and O) and inorganic components O, Mg, and Si. All samples showed cell viability above 60%. The results indicated a stable, biocompatible hybrid system that can be an alternative for topical application.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) 02817/09Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)Junta de Andalucia PT18 RT 378

Investigation into Brazilian Palygorskite for Its Potential Use as Pharmaceutical Excipient: Perspectives and Applications

Palygorskite is an aluminum and magnesium silicate characterized by its fibrous morphology, providing it with great versatility in industrial applications, including pharmaceuticals. Although most of the reserves are in the United States, in recent years occurrences of commercially exploited deposits in Brazil have been recorded, mainly in the country’s northeast region. This has motivated this study, which analyzes raw Brazilian palygorskite compared to a commercial sample (Pharmasorb® colloidal) to demonstrate its pharmaceutical potential. The chemical and mineral composition of the samples were evaluated for surface properties, granulometry, morphology, crystallography, thermal analysis, and spectroscopy. Raw palygorskite presented 67% purity, against 74% for Pharmasorb® colloidal. The percentage purity relates to the presence of contaminants, mainly carbonates and quartz (harmless under conventional conditions of pharmaceutical use). Furthermore, it was possible to confirm the chemical composition of these phyllosilicates, formed primarily of silicon, aluminum, and magnesium oxides. The crystallographic and spectroscopic profiles were consistent in both samples, showing characteristic peaks for palygorskite (2θ = 8.3°) and bands attributed to fibrous phyllosilicates below 1200 cm−1, respectively. The thermal analysis allowed the identification of the main events of palygorskite, with slight differences between the evaluated samples: loss of water adsorbed onto the surface (~85 °C), removal of water contained in the channels (~200 °C), coordinated water loss (~475 °C), and, finally, the dehydroxylation (>620 °C). The physicochemical characteristics of raw palygorskite align with pharmacopeial specifications, exhibiting a high specific surface area (122 m2/g), moderately negative charge (−13.1 mV), and compliance with the required limits for heavy metals and arsenic. These favorable technical attributes indicate promising prospects for its use as a pharmaceutical ingredient in the production of medicines and cosmetics.CAPES, grant number 88887.131333/2016-0

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake