Maria Grazia Sarpietro

Andiroba oil (AO) is an oil extracted from the seeds of Carapa guianensis , a tree native to the Amazon region, which has shown interesting biological properties, including anti‐inflammatory and antioxidant activities. AO was selected as a functional component of nanostructured lipid carriers (NLCs). Due to its biological properties, AO may represent a promising functional lipid for the development of drug delivery systems intended for the administration of therapeutic agents used in neurodegenerative diseases. In this study, AO was investigated as a novel lipid component of NLC. NLCs were prepared by the phase inversion temperature (PIT) method followed by ultrasonication. The formulations were characterized in terms of particle size (PS), polydispersity index (PDI), and zeta potential (ZP). Physicochemical properties were evaluated by differential scanning calorimetry (DSC); morphology was assessed by field‐emission scanning electron microscopy (FE‐SEM). Safety was investigated using the Hen’s egg test on the chorioallantoic membrane (HET‐CAM). Physicochemical analyses confirmed desirable parameters which remained stable throughout the 60‐day storage period. The thermotropic behaviour changed in a concentration‐dependent manner, and the formulations showed good interaction with biomembrane models. The HET‐CAM assay confirmed the safety of the formulations. In conclusion, NLC AO were successfully designed, prepared, and characterized. The incorporation of AO as a functional lipid may provide additional value beyond its role as a formulation component, supporting the future development of nanocarriers for the delivery of therapeutic agents to the brain.

Diroximel fumarate (DRF) is an orally administered prodrug used in multiple sclerosis (MS) treatment. Although it exhibits better gastrointestinal (GI) tolerability than its analogues, many patients still discontinue therapy due to frequent GI adverse events. To overcome these limitations, alternative drug delivery systems that bypass the GI tract are needed. Direct nose-to-brain delivery represents a promising approach to circumvent the blood–brain barrier and target the central nervous system; however, limited nasal mucosal absorption and the small volume of the nasal cavity pose significant challenges. Solid lipid nanoparticles (SLNs) can potentially overcome these obstacles by enhancing drug bioavailability and protecting against enzymatic degradation. This research aimed to develop an innovative intranasal nanoformulation of DRF to improve brain targeting and patient compliance. DRF-loaded SLNs were prepared using a solvent-diffusion technique with stearic acid as the lipid phase and Poloxamer 188 as the surfactant. The obtained nanoparticles displayed favorable technological characteristics, with a mean diameter of 210 nm, a polydispersity index of 0.17, and a zeta potential of −36 mV, suggesting good long-term stability. Interactions between SLNs and biomembrane models (MLV) were also studied to elucidate their cellular uptake mechanism. Future work will focus on evaluating the in vivo efficacy of this novel nanoformulation.

In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils (isopropyl myristate, decyl oleate, caprylic/capric triglyceride) to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release, skin permeation, and in vitro sun protection factor) were assessed. The optimized BMTZ-loaded NLC contained 3.0% w/w of isopropyl myristate and showed mean size = 190.6 ± 9.8 nm, polydispersity index = 0.153 ± 0.013, ζ-potential = −10.6 ± 1.7 mV, and loading capacity = 8% w/w. The incorporation of increasing concentrations (5, 10, 20% w/w) of optimized BMTZ loaded into emulsions provided a slight increase in spreadability, lower viscosity, and no change in pH, occlusion factor, and BMTZ release compared to emulsions containing free BMTZ. No BMTZ skin permeation was observed from all formulations. About a 20% increase in sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC compared with formulations incorporating the same amount of free BMTZ. Therefore, incorporating BMTZ-loaded NLC into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the nervous system that leads to neurological dysfunctions and severe disabilities. It is worth noting that conventional pharmacotherapy is poorly selective and causes toxicity problems and several systemic side effects. Thus, there is a need to develop new approaches to this medical challenge. The use of nanocarriers for drug delivery represents a good strategy to overcome several issues such as high therapeutic drug doses with side effects, such as diarrhea, nausea, and abdominal pain, and drug degradation processes; in addition, nanocarriers can provide controlled and targeted drug release. This review describes the application of liposomes for the delivery of pharmaceutical actives to target MS. Firstly, MS is explained. Then, liposomes are described along with their preparation, characterization, and stability. The literature about the use of liposomes for the treatment of MS is then analyzed.

The efficacy and safety of organic UV-filters could benefit from their incorporation into lipid nanoparticles because of the ability of such carriers to reflect solar radiations, thus acting synergically as physical sunscreens. In this work, bemotrizinol (BMTZ), a broad-spectrum UV-filter, was loaded into nanostructured lipid carriers (NLC) whose lipid matrix contained different oils to assess the effects of the lipid core composition on the properties of the resulting NLC. Subsequently, the effects of incorporating different concentrations of optimized BMTZ-loaded NLC on the technological properties of O/W emulsions (pH, viscosity, spreadability, occlusion factor, in vitro BMTZ release and skin permeation, in vitro sun protection factor) were assessed. Optimized BMTZ-loaded NLC showed mean size=190.6±9.8 nm, PDI=0.153±0.013, ζ-potential=-10.6±1.7 mV, loading capacity=8% w/w. The incorporation of increasing concentrations of optimized BMTZ-loaded into emulsions provided slight increase of spreadability, lower viscosity and no change of pH, occlusion factor and BMTZ release compared to the control. No BMTZ skin permeation was observed from all formulations. About 20% increase of sun protection factor values was obtained for vehicles containing BMTZ-loaded NLC. Therefore, BMTZ-loaded NLC incorporation into emulsions could be a promising strategy to develop safer and more effective sunscreen formulations.

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the identification of novel molecules capable of modulating VEGF effects presents promising prospects for developing therapies aimed at stabilizing, reversing, or even arresting disease progression. Lignans often suffer from low aqueous solubility and, for their use, encapsulation in a delivery system is needed. In this research, a bioinspired benzoxantene has been encapsulated in solid lipid nanoparticles that have been characterized for their pharmacotechnical properties and their thermotropic behavior. The effects of these encapsulated nanoparticles on angiogenic parameters and inflammation in VEGF-induced angiogenesis were evaluated using human brain microvascular endothelial cells (HBMECs) as a human blood–brain barrier model.

Tomato by-products represent a good source of phytochemical compounds with health properties, such as the steroidal glycoalkaloid α-tomatine (α-TM) and its aglycone tomatidine (TD). Both molecules have numerous beneficial properties, such as potential anticancer activity. Unfortunately, their therapeutic application is limited due to stability and bioavailability issues. Therefore, a valid strategy seems to be their encapsulation into Solid Lipid Nanoparticles (SLN). The nanoformulations containing α-TM (α-TM-SLN) and TD (TD-SLN) were prepared by solvent-diffusion technique and subsequently characterized in terms of technological parameters (particle size, polydispersity index, zeta potential, microscopy, and calorimetric studies). To assess the effect of α-TM and TD on the percentage of cellular viability in Olfactory Ensheathing Cells (OECs), a peculiar glial cell type of the olfactory system used as normal cells, and in SH-SY5Y, a neuroblastoma cancer cell line, an MTT test was performed. In addition, the effects of empty, α-TM-SLN, and TD-SLN were tested. Our results show that the treatment of OECs with blank-SLN, free α-TM (0.25 µg/mL), and TD (0.50 µg/mL) did not induce any significant change in the percentage of cell viability when compared with the control. In contrast, in SH-SY5Y-treated cells, a significant decrease in the percentage of cell viability when compared with the control was found. In particular, the effect appeared more evident when SH-SY5Y cells were exposed to α-TM-SLN and TD-SLN. No significant effect in blank-SLN-treated SH-SY5T cells was observed. Therefore, SLN is a promising approach for the delivery of α-TM and TD.

Sinapic acid, 3,5-dimethoxyl-4-hydroxycinnamic acid, belonging to the class of hydroxycinnamic acids, shows antioxidant, anti-inflammatory, anticancer, hepatoprotective, cardioprotective, renoprotective, neuroprotective, antidiabetic, anxiolytic, and antibacterial activity. The aim of this work was to incorporate sinapic acid into solid lipid nanoparticles in order to improve its bioavailability. SLNs were prepared using the hot high-speed homogenization method. The pharmaco-technological properties and thermotropic profile of SLNs encapsulated with sinapic acid, as well as their interaction with biomembrane models, were evaluated. SLNs showed promising physicochemical properties and encapsulation efficiency, as well as a desirable release profile; moreover, they facilitated the interaction of sinapic acid with a biomembrane model made of multilamellar vesicles. In conclusion, this formulation can be used in further studies to assess its suitability to improve sinapic acid activity.

Although mangiferin (MGN) is a natural antioxidant that could be a good candidate for the treatment of ocular diseases, its use in ophthalmology is strongly compromised due to its high lipophilicity. Its encapsulation in nanostructured lipid carriers (NLC) seems to be an interesting strategy for improving its ocular bioavailability. As reported in our previous work, MGN–NLC showed high ocular compatibility and fulfilled the nanotechnological requirements needed for ocular delivery. The aim of the present work was to investigate, in vitro and ex vivo, the capability of MGN–NLC to act as a potential drug delivery system for MGN ocular administration. The data obtained in vitro on arising retinal pigment epithelium cells (ARPE-19) did not show cytotoxic effects for blank NLC and MGN–NLC; likewise, MGN–NLC showed the maintenance of the antioxidant role of MGN by mitigating ROS (Reactive Oxygen Species) formation and GSH (glutathione) depletion induced by H₂O₂. In addition, the capacity of MGN-released to permeate through and accumulate into the ocular tissues was confirmed ex vivo using bovine corneas. Finally, the NLC suspension has been formulated as a freeze-dried powder using mannitol at a concentration of 3% (w/v) in order to optimize its storage for long periods of time. All this evidence suggests a potential application of MGN–NLC in the treatment of oxidative stress-related ocular diseases.