Atopic dermatitis (AD) is a multifactorial and widespread skin condition characterized by extreme dryness, intense itching, and compromised skin barrier function due to inflammation. The variability among patients requires constant treatment search for this skin problem, which affects children (20 %) and adults (10 %) worldwide. In this work, the use of hybrid hydrogels prepared from a blend of biocompatible marine kappa-carrageenan polysaccharide and synthetic polyvinyl alcohol polymer was thought to provide a delivery platform for betamethasone to address the features of AD. As a strategy for the local delivery of betamethasone to solve skin inflammation within its layers, this drug was also incorporated into lipid nanoparticles, which were further embedded in the hydrogel matrices to enhance its local effect and avoid side effects. The designed NLC formulations were physicochemically characterized (ca. 200 nm, polydispersity below 0.2, and surface charge of ca. -35 mV), presenting high betamethasone content (>2 mg per NLC formulation, corresponding to >= 75 % entrapment efficiency), and the hydrogels showed pseudoplastic rheological behavior. Cellular biocompatibility was verified in fibroblasts and keratinocytes in a concentration-dependent manner (tested up to 100 mg mL(-1) in hydrogel), with anti-inflammatory potential (downregulating IL-6, IL-8, and TNF-alpha secretion). Their effects on skin lipids and proteins were monitored through synchrotron-based Fourier-transform infrared microspectroscopy and full-thickness pig ear skin permeation. These hybrid formulations might represent a valuable nano-strategy and pave new treatment options for several manifestations and AD symptoms.

CONTEXT:Asparagus stipularis Forssk decoction (ASD) has shown potential metabolic and antioxidant benefits, yet its effects on pancreatic dysfunction associated with metabolic syndrome remain insufficiently explored. OBJECTIVE:The aim of this work was to assess the pancreatic protective properties of ASD in high-fructose diet (HFrD)-fed rats and to characterize ASD-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as a delivery system to enhance its therapeutic potential. METHODS:Rats were fed an HFrD and treated with ASD at two dose levels. Serum α-amylase and lipase activities were measured to assess digestive enzyme modulation. Pancreatic lipid peroxidation was quantified using thiobarbituric acid reactive substances (TBARS), while antioxidant enzyme activities, including superoxide dismutase, catalase, and glutathione peroxidase, were determined. Histopathological examination was performed to evaluate structural alterations in pancreatic tissues. ASD was encapsulated into PLGA NPs, and particle size, polydispersity index (PdI), zeta potential (ZP), and encapsulation efficiency (EE) were analyzed. RESULTS:ASD significantly reduced serum α-amylase activity to 2285.3 ± 256.6 U/L (low dose) and 1846.4 ± 82.8 U/L (high dose) compared to HFrD controls. Serum lipase activity decreased by 13% and 18% at the respective doses. TBARS levels were markedly reduced, and antioxidant enzyme activities were restored to near-control levels. Histological analysis revealed improved β-cell morphology and reduced acinar degeneration. ASD-loaded PLGA NPs exhibited a mean size of 248 ± 5 nm, PdI of 0.13 ± 0.01, ZP of -24.7 ± 1.3 mV, and an EE of 75.5 ± 3.2%. CONCLUSION:ASD demonstrates significant pancreatic protective effects, and nanoencapsulation enhances its therapeutic promise for metabolic disorders.

Resveratrol (RSV), a natural polyphenol from stilbenoids group, has gained significant interest for its numerous diverse therapeutic effects, including anti-ageing properties. Despite its potential, the bioavailability and solubility of RSV are suboptimal for topical skin administration. To overcome this, polymeric microneedles (MNs), composed of alginate alone or blended with k-carrageenan (k-CRG), were developed. In the present study, an optimized micromoulding technique was established to produce 400 mu m-long arrays. Rhodamine B (RB) was employed as a model compound for the fabrication, characterization, and selection of the most promising platform for localized dermal delivery. RB-loaded alginate-hydrogel forming MNs exhibited high skin retention (approximate to 75% of the applied dose; approximate to 0.06 mg) with minimal permeation over 24 h, whereas an RB solution resulted in higher permeation and lower apical retention. RSV-loaded MNs were subsequently fabricated and structurally characterized, demonstrating appropriate geometry and mechanical strength for skin penetration. Alginatehydrogel MNs displayed a compression force of 0.89 N, which increased to 2.37 N upon RSV loading, confirming their robustness for reliable skin insertion. RSV-loaded alginate-hydrogel forming MNs reduced apparent permeability from 3 x 10(-7) cm s(-1) (solution) to 6 x 10(-9) cm s(-1) and decreased 24 h permeation by approximately 4-fold, while retaining approximate to 2% of the initial RSV dose (approximate to 24 mu g) within the skin. Cytocompatibility assays confirmed that the formulation did not impair human keratinocyte viability at RSV concentrations up to 0.05% (w/v). Overall, these experimental data indicate that alginate-based MNs are a promising platform for the topical administration of RSV in anti-ageing applications.

Intracanal reinfections continue to pose a major challenge in endodontic treatment. Photodynamic therapy has emerged as a promising antimicrobial strategy. Regarding this, curcumin (CUR), a natural photosensitizer, shows potential in this context, but its application is hampered by poor solubility and rapid degradation. This study aimed to develop and characterize a CUR-loaded nanoparticle-enriched hydrogel to enhance its stability, sustain its release, and evaluate its antimicrobial efficacy upon photoactivation (PhAc). Curcumin-loaded nanoparticles were synthesized and incorporated into a hydrogel matrix, followed by characterization using scanning electron microscopy, Fourier-transform infrared spectroscopy, in vitro CUR release studies, and rheological analysis. Antibiofilm activity against Enterococcus faecalis was assessed under both photoactivated and non-photoactivated conditions. Cytocompatibility was analyzed through fibroblast viability assays and fluorescence staining. The CUR-containing hydrogel demonstrated a sustained release profile extending beyond 72 h. Rheological studies confirmed its shear-thinning behavior, ensuring injectability even after post-photoactivation. Antibiofilm assays revealed a significant reduction in E. faecalis biofilms, with PhAc formulations exhibiting markedly enhanced antibacterial efficacy compared to their non-PhAc counterparts. Cytocompatibility assays confirmed that all formulations, including those subjected to PDT, preserved fibroblast viability, indicating biocompatibility suitable for clinical use. In sum, the CUR-containing hydrogel exhibits properties that support its potential as an effective intracanal therapeutic, combining antimicrobial and photodynamic effects to help prevent reinfections in endodontic treatments.

Atopic dermatitis (AD) is a severe inflammatory skin disorder, affecting children and adults worldwide, and despite the several existing treatments, it is necessary to find new alternative topical therapies. Hydrogels may represent a good tool to treat AD due to their high water content, making them excellent candidates for drug delivery vehicles in skin research. This work aimed to develop and characterize hybrid hydrogels composed of gel-forming polymers (k-carrageenan and polyvinyl alcohol) for cutaneous delivery of betamethasone (up to 0.2 mg mL- 1) widely used to manage AD, with high skin retention. Bergamot oil and menthol essential oils were also incorporated into the hydrogels to study their effects on penetration and retention of the corticosteroid. Rheological properties revealed the pseudoplastic behavior of the hydrogels, a favorable characteristic for skin application. Cytocompatibility towards fibroblasts and keratinocytes was determined, revealing safe usage of the hydrogel blends up to 100 mg mL- 1, corresponding to 20 mu g mL- 1 in betamethasone, but was compromised by the presence of the essential oils in the higher hydrogel tested concentrations (50 and 100 mg mL- 1). The ex vivo pig ear skin permeation assay showed that hydrogels promote betamethasone retention up to 20 % of the added dose (c.a. 10 mu g) even after 24 h of permeation, independently of the use of essential oils' use in the composition, showing that they might be a good strategy to treat AD skin.

Background/Objectives: This study aims to evaluate the efficacy of curcumin (CUR), a natural polyphenol with potent antimicrobial and anti-inflammatory properties, when formulated as solid lipid nanoparticles (CUR-loaded SLN) against Enterococcus faecalis. Methods: Solid lipid nanoparticles (SLNs) were prepared as a carrier for CUR, which significantly improved its solubility. SLNs made with cetyl palmitate and Tween 80 were obtained via the hot ultrasonication method. The physicochemical properties of CUR-loaded SLNs were evaluated, including their size, stability, and release profile. Antimicrobial testing was conducted against both sessile and planktonic E. faecalis populations. Cytotoxicity was assessed on human gingival fibroblasts. Results: The CUR-loaded SLNs exhibited about 200 nm and a −25 mV surface potential, and the encapsulation of CUR did not affect the physicochemical properties of SLNs. CURs were released from SLNs in a controlled and sustained manner over 100 h. The nanoparticles remained stable for at least two months when stored at 4 °C or 25 °C, making them suitable for clinical use. Antioxidant activity was confirmed through DPPH and ABTS assays. Free CUR significantly reduced the planktonic E. faecalis CFU counts by approximately 65% after 24 h of exposure. However, this inhibitory effect diminished with longer exposure times (48 and 72 h). Antimicrobial activity studies of CUR-loaded SLNs showed dose- and time-dependent effects, in the 2.5–10 µg/mL range, against both sessile and planktonic E. faecalis populations, over 24 to 72 h. The CUR-loaded SLNs showed good cytocompatibility with human fibroblasts up to 2.5 μg/mL, suggesting low toxicity. Conclusions: CUR-loaded SLNs demonstrate significant antimicrobial activity against E. faecalis, along with good cytocompatibility, indicating their potential as an effective adjunct therapy in endodontic treatments.

Nanoparticle-embedded hydrogels are promising delivery systems for cutaneous applications. This study aimed to enhance skin delivery and bioavailability of quercetin, a biologically active flavonoid using nanostructured lipid carriers (NLCs) embedded within sodium alginate/ poly(vinyl alcohol) hydrogels. Pomegranate oil, selected for its anti-inflammatory, antioxidant, and anti-apoptotic properties, served as a natural liquid lipid for NLCs production. A Box-Behnken design optimized the NLC production, considering the lipid ratio, water content, and drug concentration as variables. The resulting NLCs (200 to 300 nm) achieved 55 % quercetin entrapment efficiency, outperforming solid lipid nanoparticles (43 %). The NLCs showed long-term colloidal stability (3 months) with a surface potential of -19 ± 3 mV, maintained through combined electrostatic and steric stabilization mechanisms. While quercetin's antioxidant activity slightly decreased when encapsulated. Cellular viability was demonstrated in fibroblasts and keratinocytes. Rheological analysis confirmed the hydrogels' robustness and stability, while Human keratinocytes studies indicated a photoprotective effect, making this delivery system a promising approach for preventing UVB-induced skin damage.

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Human skin ageing is closely related to the ageing of the whole organism, and it's a continuous multisided process that is influenced not only by genetic and physiological factors but also by the cumulative impact of environmental factors. Currently, there is a scientific community need for developing skin models representing ageing processes to (i) enhance understanding on the mechanisms of ageing, (ii) discover new drugs for the treatment of age-related diseases, and (iii) develop effective dermo-cosmetics. Bioengineers worldwide are trying to reproduce skin ageing in the laboratory aiming to better comprehend and mitigate the senescence process. This review provides details on the main ageing molecular mechanisms and procedures to obtain in vitro aged skin models.

Skin acts as a dynamic interface with the environment. Pathological alterations in the skin barrier are associated with skin diseases. These conditions are characterized by specific impairments in epidermal barrier functions.Despite its protective nature, the skin can be a relevant route of drug administration, both for topical and transdermal therapy, allowing for improved drug delivery and reducing the incidence of adverse reactions.This manuscript reviews transcutaneous drug delivery as a strategy for treating localized and systemic conditions, highlighting the importance of skin models in the evaluation of drug efficacy and barrier function. It explores advances in in vitro, ex vivo, in vivo, and in silico models for studying cellular uptake, wound healing, oxidative stress, anti-inflammatory and immune modulation activities. Disease-specific skin models are also discussed.

To address the challenges posed by biofilm presence and achieve a substantial reduction in bacterial load within root canals during endodontic treatment, various irrigants, including nanoparticle suspensions, have been recommended. Berberine (BBR), a natural alkaloid derived from various plants, has demonstrated potential applications in dentistry treatments due to its prominent antimicrobial, anti-inflammatory, and antioxidant properties. This study aimed to produce and characterize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with berberine and evaluate its antimicrobial activity against relevant endodontic pathogens, Enterococcus faecalis, and Candida albicans. Additionally, its cytocompatibility using gingival fibroblasts was assessed. The polymeric nanoparticle was prepared by the nanoprecipitation method. Physicochemical characterization revealed spheric nanoparticles around 140 nm with ca, −6 mV of surface charge, which was unaffected by the presence of BBR. The alkaloid was successfully incorporated at an encapsulation efficiency of 77% and the designed nanoparticles were stable upon 20 weeks of storage at 4 °C and 25 °C. Free BBR reduced planktonic growth at ≥125 μg/mL. Upon incorporation into PLGA nanoparticles, 20 μg/mL of [BBR]-loaded nanoparticles lead to a significant reduction, after 1 h of contact, of both planktonic bacteria and yeast. Sessile cells within biofilms were also considered. At 30 and 40 μg/mL, [BBR]-loaded PLGA nanoparticles reduced the viability of the sessile endodontic bacteria, upon 24 h of exposure. The cytotoxicity of BBR-loaded nanoparticles to oral fibroblasts was negligible. The novel berberine-loaded polymeric nanoparticles hold potential as a promising supplementary approach in the treatment of endodontic infections.

Biological barriers prevent nanotherapeutics successful accumulation at target cells, limiting diagnosis and treatment responses. Magnetic nanodiscs with a spin-vortex ground state have shown great promise for magnetomechanical cancer cells annihilation and for neuronal stimulation, requiring very low concentrations for an effective result. However, the biological barriers that these particles encounter upon intravenous administration remain a challenge. Herein, the synthesis of biocompatible multilayered Au/Fe/Au nanodiscs with a spin-vortex ground state and their inert surface modification is reported. Two different surface modifications with two distinct polyethylene glycol (PEG) molecules are performed, which successfully reduce macrophage uptake, while maintaining the nanodiscs' biocompatibility. By effectively preventing nanodisc uptake, innovative design features can be rationally incorporated to create a new generation of specific nanotherapeutics by modifying the PEG surface with specific targeting molecules. Biological barriers prevent nanotherapeutics successful accumulation at target cells, limiting diagnosis and treatment responses. The surface of magnetic nanodiscs in a spin-vortex ground state is modified with polyethylene glycol (PEG) molecules, which allow a reduction of the macrophage's uptake, while maintaining the nanodiscs' biocompatibility. By successfully preventing the nanodiscs uptake, innovative design features can be rationally incorporated to create a new generation of specific nanotherapeutics by modifying the PEG surface with specific targeting molecules.image (c) 2024 WILEY-VCH GmbH

Ruthenium-based complexes have been suggested as promising anticancer drugs exhibiting reduced general toxicity compared to platinum-based drugs. In particular, Ru(η6-arene)(PTA)Cl2 (PTA = 1,3,5-triaza-7-phosphaadamantane), or RAPTA, complexes have demonstrated efficacy against breast cancer by suppressing metastasis, tumorigenicity, and inhibiting the replication of the human tumor suppressor gene BRCA1. However, RAPTA compounds have limited cytotoxicity, and therefore comparatively high doses are required. This study explores the activity of a series of RAPTA-like ruthenium(II) arene compounds against MCF-7 and MDA-MB-231 breast cancer cell lines and [Ru(η6-toluene)(PPh3)2Cl]+ was identified as a promising candidate. Notably, [Ru(η6-toluene)(PPh3)2Cl]Cl was found to be remarkably stable and highly cytotoxic, and selective to breast cancer cells. The minor groove of DNA was identified as a relevant target.

There is a growing need for alternatives to target and treat bacterial infection. Thus, the present work aims to develop and optimize the production of PEGylated magnetoliposomes (MLPs@PEG), by encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) within fusogenic liposomes. A Box-Behnken design was applied to modulate size distribution variables, using lipid concentration, SPIONs amount and ultrasonication time as independent variables. As a result of the optimization, it was possible to obtain MLPs@PEG with a mean size of 182 nm, with polydispersity index (PDI) of 0.19, and SPIONs encapsulation efficiency (%EE) around 76%. Cytocompatibility assays showed that no toxicity was observed in fibroblasts, for iron concentrations up to 400 mu g/ml. Also, for safe lipid and iron concentrations, no hemolytic effect was detected. The fusogenicity of the nanosystems was first evaluated through lipid mixing assays, based on Forster resonance energy transfer (FRET), using liposomal membrane models, mimicking bacterial cytoplasmic membrane and eukaryotic plasma membrane. It was shown that the hybrid nanosystems preferentially interact with the bacterial membrane model. Confocal microscopy and fluorescence lifetime measurements, using giant unilamellar vesicles (GUVs), validated these results. Overall, the developed hybrid nanosystem may represent an efficient drug delivery system with improved targetability for bacterial membrane.

Berberine, an isoquinoline alkaloid extracted from plants of the Berberidaceae family, has been gaining interest due to anti-inflammatory and antioxidant activities, as well as neuro and cardiovascular protective effects in animal models. Recently, photodynamic therapy demonstrated successful application in many fields of medicine. This innovative, non-invasive treatment modality requires a photosensitizer, light, and oxygen. In particular, the photosensitizer can selectively accumulate in diseased tissues without damaging healthy cells. Berberine’s physicochemical properties allow its use as a photosensitising agent for photodynamic therapy, enabling reactive oxygen species production and thus potentiating treatment efficacy. However, berberine exhibits poor aqueous solubility, low oral bioavailability, poor cellular permeability, and poor gastrointestinal absorption that hamper its therapeutic and photodynamic efficacy. Nanotechnology has been used to minimize berberine’s limitations with the design of drug delivery systems. Different nanoparticulate delivery systems for berberine have been used, as lipid-, inorganic- and polymeric-based nanoparticles. These berberine nanocarriers improve its therapeutic properties and photodynamic potential. More specifically, they extend its half-life, increase solubility, and allow a high permeation and targeted delivery. This review describes different nano strategies designed for berberine delivery as well as berberine’s potential as a photosensitizer for photodynamic therapy. To benefit from berberine’s overall potential, nanotechnology has been applied for berberine-mediated photodynamic therapy.

Astaxanthin (ASTA) and zeaxanthin (ZEA) are xanthophyll carotenoids showing a wide spectrum of health-promoting properties. However, their utilization is limited, mostly due to poor water solubility, limited bioavailability, and a tendency to oxidate, as well as photo- and thermal instability. The aim of this work was to develop ASTA- and ZEA-loaded nano-structured lipid carriers (NLCs) that would protect them against degradation and improve their intestinal stability/permeability. Obtained NLCs were characterized by an effective diameter of 294 nm for ASTA-NLC and 280 nm for ZEA-NLC; polydispersity index (PDI) lower than 0.2; and zeta potential of –29.4 mV and –29.0 mV, respectively. Interestingly, despite similar physicochemical characteristics, our investigation revealed differences in the encapsulation efficiency of ASTA-NLC and ZEA-NLC (58.0 % vs. 75.5 %, respectively). Obtained NLCs were stable during a 21 day-storage period in the dark at room temperature or at 4 °C. Investigation of gastrointestinal stability showed no change in effective diameter and PDI under gastric conditions while both parameters significantly changed under intestinal conditions. Our results showed for the first time that both ASTA- and ZEA-NLCs intestinal absorption investigated in the in vitro model is significantly increased (in relation to pure compounds) and is affected by the presence of mucus. This study provides useful data about the advantages of using NLC as a delivery system for ASTA and ZEA that might facilitate their applications in the food and pharmaceutical industry.

Understanding how nanoparticles' properties influence their cellular interactions is a bottleneck for improving the design of carriers. Macrophage polarization governs their active role in solving infections or tissue repair. To unravel the effect of carbohydrate-targeting mannose receptors on the macrophage surface, drug-free fucoidan/chitosan nanoparticles were functionalized using mannose (M) and mannan (Mn). Polyelectrolyte complex nanoparticles were obtained upon chitosan self-assembly using fucoidan. The functionalized nanoparticles were characterized in terms of their physicochemical characteristics, chemical profile, and carbohydrate orientation. The nanoparticles varied in size from 200 to 400 nm, were monodisperse, and had a stable negative zeta potential with a low aggregation tendency. The nonfunctionalized and functionalized nanoparticles retained their properties for up to 12 weeks. Cell viability and internalization studies were performed for all the designed nanoparticles in the THP-1 monocytes and THP-1-differentiated macrophages. The expression of the mannose receptor was verified in both immune cells. The carbohydrate-functionalized nanoparticles led to their activation and the production of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α. Both M- and Mn-coated nanoparticles modulate macrophages toward an M1-polarized state. These findings demonstrate the tailoring of these nanoplatforms to interact and alter the macrophage phenotype in vitro and represent their therapeutic potential either alone or in combination with a loaded drug for future studies.

Lipid-based nanoplatforms appear to be one of the most promising groups of biomaterials for skin delivery. This is due to their favourable physicochemical, mechanical and safety properties. Gel-like matrices play an important role in medicine, pharmacy and cosmetology. The aim of the present study was to obtain a gel-like matrix based on freeze-dried nanostructured lipid carriers prepared with Softisan (R) 649 and Miglyol (R) 812 for the dermal delivery of genistein. The nanostructured lipid carriers were prepared and characterised by the hot ultrasound method. Genistein-loaded nanoparticles have a size around 235 nm, similar to empty nanoparticles (225 nm), and show storage stability up to 12 weeks at room temperature. Nanoencapsulation protected genistein from photodegradation and preserved its antioxidant activity. Biocompatibility assays showed that neither genisteinloaded nor empty lipid nanoparticles adversely affected HaCaT cell viability up to 100 mu g mL-1 of genistein, while the IC50 of free genistein was 68.7 mu g mL-1. The lipid nanoparticles were freeze-dried to obtain a gel-like matrix. The presence of genistein slightly reduces the swelling ability of the lipid-based gels, the gel-like matrix shows non-thixotropic behaviour and good resistance to deformation, which is not affected by the presence of genistein, indicating the stability of the nanoformulation. In vitro skin permeation assays show an increased skin deposition of genistein for the gel-like formulation compared to free isoflavone. The data obtained in the present study demonstrate the potential of the gel-like matrix to deliver genistein to the skin, suggesting a promising application as a supplement for sun protection and skin diseases associated with solar UV radiation.

Marine polysaccharides are recognized for their biological properties and their application in the drug delivery field, favoring hydrogel-forming capacities for cutaneous application towards several dermatological conditions. Essential oils have been widely used in skin, not only for their remarkable biological properties, but also for their capacity to enhance permeation through the skin layers and to confer a pleasant scent to the formulation. In this study, menthol, L-linalool, bergamot oil, and β-pinene were incorporated in alginate/fucoidan hydrogels to evaluate their skin permeation enhancement profile and assess their influence on the skin organization. The combinations of different essential oils with the marine-based fucoidan/alginate hydrogel matrix were characterized, resulting in formulations with pseudoplastic rheological properties favorable for a uniform application in the skin. The ex vivo Franz diffusion permeation assays revealed that calcein loaded in bergamot-alginate/fucoidan hydrogel permeated more than 15 mg out of the initial 75 mg than when in linalool-alginate/fucoidan, alginate/fucoidan or hydrogel without any incorporated oil. Skin calcein retention for menthol- and pinene-alginate/fucoidan hydrogels was 15% higher than in the other conditions. Infrared micro-spectroscopic analysis through synchrotron-based Fourier Transform Infrared Microspectroscopy evidenced a symmetric shift in CH3 groups towards higher wavenumber, indicating lipids’ fluidization and less lateral packing, characterized by a band at 1468 cm−1, with the bergamot-alginate/fucoidan, which contributes to enhancing skin permeation. The study highlights the effect of the composition in the design of formulations for topical or transdermal delivery systems.