Modern medicine has made significant progress by incorporating natural bioactive compounds, not only as active ingredients but also as functional excipients. This study aimed to develop naturally derived nanostructured lipid carriers (NLCs) containing (3-caryophyllene as a therapeutic adjuvant for the treatment of skin cancer. To identify the optimal combination among passion fruit oil, beeswax, soy lecithin, and (3-caryophyllene, a component screening was performed. The formulations' stability was monitored by particle size analysis and macroscopic evaluation over 30 days. Transmission electron microscopy of the optimized systems revealed the typical spherical morphology of NLCs. They exhibited drug entrapment efficiency higher than 92%. The lipid matrix, surrounded by the surfactant layer, effectively protected (3-caryophyllene from volatilization. The release profile appeared to follow anomalous transport behavior. Photoacoustic spectroscopy indicated that (3-caryophyllene could permeate into the dermis. Two selected systems (F3 and F21) enhanced the cytotoxic selectivity of (3-caryophyllene against representative melanoma cells (B16-F10), with selectivity indices of 2.07 and 2.2, respectively. Overall, the developed systems demonstrated physicochemical and therapeutic characteristics that support their potential as adjuvants for the topical treatment of skin cancer. Future in vivo studies are warranted to confirm this potential.

Skin cancer represents a global health challenge with rising incidence rates, requiring the development of comprehensive therapeutic strategies. Although conventional therapies, both local (surgery, radiotherapy) and systemic (chemotherapy, immunotherapy, molecular therapy), remain the cornerstone of managing various types of skin cancer, nanotechnology approaches now represent the cutting edge of skin cancer treatment, offering targeted drug delivery and reduced systemic toxicity. However, some limits on clinical transfer are still present. This review examines current treatment modalities ranging from conventional approaches to emerging nanotechnological innovations, such as lipid-based nanosystems (vesicles, solid lipid nanoparticles), as well as polymeric nanocarriers (nanospheres, nanocapsules, dendrimers, polymeric micelles) and new programmable nanocarriers (framework nucleic acids and microneedles) in the treatment of the most aggressive skin cancers, such as basal cell, squamous cell carcinomas and melanoma. These delivery nanosystems demonstrate superior biocompatibility, controlled drug release, enhanced therapeutic efficacy compared to conventional formulations and treatments, enabling size-dependent skin penetration and effectively reaching dermal layers, avoiding off-target effects. Therefore, the integration of traditional therapeutic approaches with nano-technological systems represent a promising strategy to enhance patient outcomes by providing personalized, targeted treatment strategies in the management of skin cancer.

It is known that the overproduction of reactive oxygen species (ROS), which regulate numerous physiological processes, can generate oxidative stress, responsible for the onset of several pathologies [...].

This study presents the development of supramolecular nanosystems for the topical administration of rutin (RU), focusing on β-cyclodextrin (Cy) complexes and their inclusion in liposomes (CyL) in a 4:1 molar ratio. The supramolecular nanosystems were obtained by the “thin film hydration” method, and characterized in terms of size, morphology, encapsulation efficiency, antioxidant activity and skin safety, by DLS, transmission electron microscopy, UV spectrometry, DPPH radical liberation assay and patch test, respectively. Rutin release kinetics was determined by Franz cell experiments. The resulting CyL loaded with RU formed stable, homogeneous vesicular dispersions, maintaining color, size, and polydispersity over 30 days, with rutin content consistently above 90

In the original publication [...].

Oxidative stress is one of the key elements in lung-related complications such as cystic fibrosis, acute lung injury, pulmonary hypertension, bronchopulmonary dysplasia, chronic airway diseases, lung cancer, COVID-19, and many others. Antioxidant and anti-inflammatory therapy can be considered as supportive alternatives in their management. However, most naturally derived antioxidants face issues with poor aqueous solubility and stability, which hinder their clinical utility. Remarkably, local pulmonary delivery circumvents the severe limitations of oral delivery, including hepatic first-pass metabolism and organ toxicity, and enables a higher drug payload in the lungs. Here, in this review, we present cyclodextrin as a potential drug carrier for pulmonary administration, exploring the possibilities of its surface modification, complexation with other drug transporters, and loading of cannabidiols, siRNA, and antibodies as future trends. However, the lack of a robust physiological model for assessing the efficacy of lung-oriented drug targeting is a significant concern in its path to clinical and commercial success.

Liposomes are lipid bilayer vesicles that are highly biocompatible, able to interact with the cell membrane, and able to release their cargo easily. The improvement of the physicochemical properties of liposomes, such as surface charge, lipid composition, and functionalization, makes these vesicles eligible delivery nanosystems for the gene therapy of many pathological conditions. In the present study, pre-formulation analysis was conducted to develop liposomes that facilitate the delivery of nucleic acids to neuronal cells, with the aim of future delivery of a CRISPR/Cas9 system designed to silence genes responsible for autosomal dominant neurodegenerative disorders. To this aim, different nucleic acid cargo models, including λ phage DNA, plasmid DNA, and mRNA encoding GFP, were considered. Liposomes with varying lipid compositions were produced using the ethanol injection method and analyzed for their dimensional stability and ability to interact with DNA. The selected formulations were tested in vitro using a neuroblastoma cell line (SH-SY5Y) to evaluate their potential toxicity and the ability to transfect cells with a DNA encoding the green fluorescent protein (pCMV-GFP). Among all formulations, the one containing phosphatidylcholine, phosphatidylethanolamine, pegylated 1,2-distearoyl-sn-glycero-3-phosphethanolamine, cholesterol, and dioctadecyl-dimethyl ammonium chloride (in the molar ratio 1:2:4:2:2) demonstrated the highest efficiency in mRNA delivery. Although this study was designed with the goal of ultimately enabling the delivery of a CRISPR/Cas9 system for treating autosomal dominant neurodegenerative disorders such as polyglutamine spinocerebellar ataxias (SCAs), CRISPR/Cas9 components were not delivered in the present work, and their application remains the objective of future investigations.

The flavonoid rutin is an active ingredient with multiple health benefits featuring antioxidant, anti-inflammatory, cardiovascular, neuroprotective, anti-diabetic and anti-tumor activity, unfortunately characterized by physico-chemical instability and poor solubility in aqueous environment. The present study investigates the use of nanosystems for the delivery of rutin through oral administration for a possible dietary supplementation. In this view, rutin-containing cyclodextrins and rutin-in-cyclodextrin-in-liposomes (R-CL) have been studied. R-CL, obtained by the “thin film hydration” method, were initially homogeneous in size, but increased in the average diameter over time. R-CL showed greater encapsulation efficiency and stability of rutin over time compared to cyclodextrin complexes. R-CL were stable in term of rutin content and physically within 30 days of storage in a cool environment, showing no phase separation phenomena. The dialysis study through a Wistar rat small intestine fragment, demonstrated an increasing release of rutin from R-CL, reaching the plateau around the sixth hour. The use of a gastrointestinal fluid simulator within the selected biological fragment, led to a more linear and gradual release profile over time, still obtaining a complete release of the drug around the sixth hour. The in vitro experiments on HepG2 cells evidenced no cytotoxic effect for both R-CL and cyclodextrin-complex and a strong and significant increase in glucose uptake levels promoted by R-CL with respect to untreated cells, as well as to the other formulations. The data suggest that the formulation strategy based on the vesicular cyclodextrin system improves the biological effect of rutin on cells. However, further studies will be necessary to confirm the activity of rutin as food supplementation.

Naturally available antioxidants offer remarkable medicinal applications in wound healing. However, the encapsulation of these phytoactive moieties into suitable nano-scale drug delivery systems has always been challenging due to their inherent characteristics, such as low molecular weight, poor aqueous solubility, and inadequate skin permeability. Here, we provide a systematic review focusing on the major obstacles hindering the development of various lipid and polymer-based drug transporters to carry these cargos to the targeted site. Additionally, this review covers the possibility of combining the effects of a polymer and a lipid within one system, which could increase the skin permeability threshold. Moreover, the lack of suitable physical characterization techniques and the challenges associated with scaling up the progression of these nano-carriers limit their utility in biomedical applications. In this context, consistent progressive approaches for addressing these shortcomings are introduced, and their prospects are discussed in detail.

The use of in vitro markers able to reproduce the in vivo permeability and diffusivity of orally administered drugs, could represent an innovative starting point for the formulation of delivery systems, in particular for low soluble and low permeable drugs belonging to BCS class II and IV. Considering the great interest in the green pharmaceutical approaches and the increasing use of natural molecules as novel therapeutic drugs, in this study, rutin, hesperidin and curcumin have been selected as lipophilic model drugs to investigate their possible enhancement of their permeability and bioavailability after oral administration. As the low solubility of the three drugs hinders their application, β-cyclodextrins (CD), amphiphilic natural moieties able to form stable inclusion complexes, have been considered to promote their solubilization. Notably, hydroxypropyl-β-CD (HPBCD) and methyl-β-CD (MBCD), have been selected and the formation of the inclusion complexes with a stoichiometric ratio of 1:1 has been detected through phase-solubility studies and rationalized via docking calculations, revealing a strong complexation and an increased hydrophilicity of the systems. The diffusion experiments performed through the novel UV-Vis localized spectroscopy method confirmed a the extremely high stability of the CD-drugs complexes, especially in the cease of curcumin, which makes this as the predominant chemical specie to diffuse and permeates. The PermeaPad® plate, an in vitro cell-free assay, allowed to investigate the permeability behavior of the drugs, demonstrated that the type of β-cyclodextrins can influence the permeability through the biomimetic membrane, reflecting the effect of the unstirred water layer (UWL). Moreover, in the case of curcumin, the spectroscopic-mathematical approach suggested the formation of nano-supramolecular systems, detected by DLS, supporting the precision of the fitting model.

Paper-based packaging is experiencing a resurgence due to its inherent biodegradability and recyclability. To meet the barrier properties required for certain applications, a coating is necessary. This coating must enhance functionality without compromising the environmental sustainability of the substrate. With this goal in mind, we prepared waterborne dispersions of biodegradable poly(lactic acid) (PLA) using a PEG-PLA-PEG triblock copolymer as the main surfactant. We achieved formulations with good stability over a 6-month period and high solids content (similar to 40 wt%). The waterborne dispersions underwent analysis by dynamic light scattering (DLS), size exclusion chromatography (SEC), gravimetric tests, and rotational rheology with and without xanthan gum (0.2-0.8 wt%) as a thickener. Subsequently, the thickened dispersions were coated at 60 degrees C onto a paper substrate. SEM analyses revealed the formation of a polymer layer on the paper surface with thickness and morphology dependent on the processing conditions. Partial interpenetration between the coating and the paper fibers was observed, resulting in excellent adhesion between the layers. The coated paper exhibited good barriers to liquid and water vapor, with Cobb60 < 5 g/m(2) and water vapor transmission rate (WVTR) < 100 g/(m(2)center dot day) for coating weights <= 15 g/m(2), comparable to the performance of solvent-based PLA paper coatings. The surface energy of the coating was approximately 50 dyne/cm, higher than that of neat PLA, making it suitable for printing with common inks. Furthermore, the coated paper can be fully pulped in water, indicating that it can still be recycled in the paper stream, albeit with potentially increased processing time due to the coating weight.

The regulation of numerous physiological processes is strictly dependent on the production of reactive oxygen species (ROS) [...]

The present study investigates the possible use of manganese (Mn)-based liposomal formulations for diagnostic applications in imaging techniques such as magnetic resonance imaging (MRI), with the aim of overcoming the toxicity limitations associated with the use of free Mn2+. Specifically, anionic liposomes carrying two model Mn(II)-based compounds, MnCl2 (MC) and Mn(HMTA) (MH), were prepared and characterised in terms of morphology, size, loading capacity, and in vitro activity. Homogeneous dispersions characterised mainly by unilamellar vesicles were obtained; furthermore, no differences in size and morphology were detected between unloaded and Mn-loaded vesicles. The encapsulation efficiency of MC and MH was evaluated on extruded liposomes by means of ICP-OES analysis. The obtained results showed that both MC and MH are almost completely retained by the lipid portion of liposomes (LPs), with encapsulation efficiencies of 99.7% for MC and 98.8% for MH. The magnetic imaging properties of the produced liposomal formulations were investigated for application in a potential preclinical scenario by collecting magnetic resonance images of a phantom designed to compare the paramagnetic contrast properties of free MC and MH compounds and the corresponding manganese-containing liposome dispersions. It was found that both LP-MC and LP-MH at low concentrations (0.5 mM) show better contrast (contrast-to-noise ratios of 194 and 209, respectively) than solutions containing free Mn at the same concentrations (117 and 134, respectively) and are safe to use on human cells at the selected dose. Taken together, the results of this comparative analysis suggest that these liposome-containing Mn compounds might be suitable for diagnostic purposes.

In the original publication [...].

INTRODUCTION:Wounds, resulting from traumas, surgery, burns or diabetes, are important medical problems due to the complexity of wound healing process regarding healing times and healthcare costs. Nanosystems have emerged as promising candidates in this field thank to their properties and versatile applications in drugs delivery. AREAS COVERED:Lipid-based nanosystems (LBN) are described for wound treatment, highlighting their different behaviors when interacting with the cutaneous tissue. The role of nanosystems in delivering mostly natural compounds on skin as well as the technological and engineering strategies to increase their efficiency in wound healing effect are reviewed. Finally, in vitro, ex-vivo and in vivo studies are reported. EXPERT OPINION:LBN have shown promise in addressing the challenges of wound healing as they can improve the stability of drugs used in wound therapy, leading to higher efficacy and fewer adverse effects as compared to traditional formulations. LBNs being involved in the inflammatory and proliferation stages of the wound healing process, enable the modification of wound healing through multiple ways. In addition, the use of new technologies, including 3D bioprinting and photobiomodulation, may lead to potential breakthroughs in wound healing. This would provide clinicians with more potent forms of therapy for wound healing.

The use of lipid-based nanosystems for topical administration represents an innovative "green" approach, being composed of materials, defined as GRAS (generally recognized as safe), characterized by low toxicity, biocompatibility, and biodegradability [...].

In this study, we examined and compared two different lipid-based nanosystems (LBNs), namely Transferosomes (TFs) and Monoolein Aqueous Dispersions (MADs), as delivery systems for the topical application of Ferulic Acid (FA), an antioxidant molecule derived from natural sources. Our results, as demonstrated through Franz-cell experiments, indicate that the LBNs produced with poloxamer 188 in their composition create a multilamellar system. This system effectively controls the release of the drug. Nonetheless, we found that the type of non-ionic surfactant can impact the drug release rate. Regarding FA diffusion from the MAD, this showed a lower diffusion rate compared with the TF. In terms of an in vivo application, patch tests revealed that all LBN formulations tested were safe when applied under occlusive conditions for 48 h. Additionally, human skin biopsies were used to determine whether FA-containing formulations could influence skin tissue morphology or provide protection against O3 exposure. Analyses suggest that treatment with TFs composed of poloxamer 188 and MAD formulations might protect against structural skin damage (as observed in hematoxylin/eosin staining) and the development of an oxidative environment (as indicated by 4-hyroxinonenal (4HNE) expression levels) induced by O3 exposure. In contrast, formulations without the active ingredient did not offer protection against the detrimental effects of O3 exposure.Inizio modulo.

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application.

The nanoparticles designed for application in cancer treatment should have biocompatibility, colloidal stability and triggered release at tumor sites. Magnetic nanoparticles arise as an interesting option to be used as drug nanocarriers, considering the possibility of driving nanoparticles to the correct delivery site and exploring different triggers to achieve such accomplishment. In this study, nickel ferrite nanoparticles are explored as a magnetic core for drug delivery systems, using doxorubicin and omeprazole as model drugs. The developed nickel ferrite presents a strong superparamagnetic behavior and high purity, as demonstrated by magnetometry and TGA results. The carbon-coating procedure and functionalization allowed the nanoparticle to achieve the desired characteristics for biomedical applications (i.e. stability in water, biocompatibility, and size). According to TEM results, the final carbon-coated magnetic nanoparticles have an average size of 25.09 +/- 0.58 nm and multi-core shell architecture, which is suitable for biomedical applications as drug nanocarriers. In addition, DLS demonstrated that functionalized nanoparticles are monodisperse, with a hydrodynamic diameter of 167 +/- 59 nm, which fits the recommended range (100-200 nm) to benefit from enhanced permeability and retention effect. Drug loading tests with doxorubicin and omeprazole revealed the versatility of the designed nanoparticles, able to load 97% of doxorubicin and 51% of omeprazole. The pH-triggered release was also confirmed for both pharmacological compounds, showing a higher cumulative drug under acidic conditions (simulating a tumor microenvironment). Finally, the kinetic analysis applied to the study of the release mechanism of both medicines showed that non-linear models fit with higher accuracy the experimental data.

Nanomaterials possess outstanding attributes due to nanoscale effects and increased surface area, which influence interactions with biomolecules, cells, and the biological system. They have been envisaged to play an important role in biosensors, bioimaging, and gene and drug delivery applications. Properties, including size, morphology, composition, zeta potential, and structure, control their specific interactions on the cellular level. Calcium phosphates (CPs), the primary component of natural hard tissue, are bequeathed with commendable properties, including biocompatibility, bioactivity, tunable biodegradability, that depends on the Ca/P molar ratio and nontoxicity. In addition, the dissolution rate of CPs can be contained by adjusting its crystallinity, thereby potentially promoting the development of efficient and controlled delivery systems. This chapter focuses on the biological properties of CP nanoparticles, including their limited toxicity. It also describes the various mechanisms in drug loading, targetability, and the uses of CPs as drug and gene delivery agents. The chapter also includes a brief overview of CPs as theranostic agents.