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Ovarian cancer is one of the deadliest epithelial malignancies in women, owing to the multidrug resistance that restricts the success of conventional chemotherapy, carboplatin and paclitaxel. High grade serous ovarian carcinoma can be classified into two subtypes, the chemosensitive High OXPHOS and the Low OXPHOS tumour, less sensitive to chemotherapy. This difference of treatment efficacy could be explained by the redox status of these tumours, High OXPHOS exhibiting a chronic oxidative stress and an accumulation of reactive oxygen species. Ferrocifens, bio-organometallic compounds, are believed to be ROS producers with a good cytotoxicity on ovarian cancer cell lines. The aim of this study was to evaluate the in vivo efficacy of ferrocifen stealth lipid nanocapsules on High and Low OXPHOS ovarian Patient-Derived Xenograft models, alone or in combination to standard chemotherapy. Accordingly, two ferrocifens, P53 and P722, were encapsulated in stealth LNCs. The treatment by stealth P722-LNCs in combination with standard chemotherapy induced, with a concentration eight time lower than in stealth P53-LNCs, similar tumour reduction on a Low OXPHOS model, allowing us to conclude that P722 could be a leading ferrocifen to treat ovarian cancer. This combination of treatments may represent a promising synergistic approach to treat resistant ovarian adenocarcinoma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: [Catherine Passirani reports financial support was provided by French National Research Agency. Pierre Idlas, Elise Lepeltier, Catherine Passirani reports equipment, drugs, or supplies was provided by SME Feroscan. Pierre Idlas, Catherine Passirani, Elise Lepeltier reports administrative support was provided by COST Action STRATAGEM, CA17104]., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Glioblastoma is the most common and lethal malignant brain tumor. Despite simvastatin (SVT) showing potential anticancer properties, its antitumoral effect against glioblastoma appears limited when the conventional oral administration route is selected. As a consequence, nose-to-brain delivery has been proposed as an alternative route to deliver SVT into the brain. This study aimed to prepare chitosan-coated simvastatin-loaded lipid-core nanocapsules (LNC SVT-chit ) suitable for nose-to-brain delivery and capable of fostering antitumor effects against glioblastoma both in vitro and in vivo. Results showed that the nanocapsules present adequate particle size (mean diameter below 200 nm), narrow particle size distribution (PDI < 0.2), positive zeta potential and high encapsulation efficiency (nearly 100%). In vitro cytotoxicity of LNC SVT-chit was comparable to non-encapsulated SVT in C6 rat glioma cells, whereas LNC SVT-chit were more cytotoxic than non-encapsulated SVT after 72 h of incubation against U-138 MG human glioblastoma cell line. In studies carried out in rats, LNC SVT-chit significantly enhanced the amount of drug in rat brain tissue after intranasal administration (2.4-fold) when compared with free SVT. Moreover, LNC SVT-chit promoted a significant decrease in tumor growth and malignancy in glioma-bearing rats in comparison to control and free SVT groups. Additionally, LNC SVT-chit did not cause any toxicity in treated rats. Considered overall, the results demonstrated that the nose-to-brain administration of LNC SVT-chit represents a novel potential strategy for glioblastoma treatment., (Copyright © 2022. Published by Elsevier B.V.)

(R)-CE3F4, a specific inhibitor of EPAC1 (exchange protein directly activated by cAMP type 1), has been demonstrated in vitro and in vivo to reduce hypertrophic signaling contributing to heart failure or to control arrhythmia and has shown promise as a drug candidate. However, (R)-CE3F4 exhibits poor solubility in aqueous media and has shown sensitivity to enzyme hydrolysis in plasma. To overcome these issues, the drug was entrapped in liposomes and lipid nanocapsules. Both systems considerably increased the drug apparent solubility in aqueous media. Among these nanocarriers, lipid nanocapsules offered significant protection in vitro against enzymatic degradation by increasing the (R)-CE3F4 apparent half-life from around 40 min to 6 h. Pharmacokinetics and biodistribution of (R)-CE3F4 radiolabeled or not were studied in healthy C57BL/6 mice. The non-encapsulated 3 H-CE3F4 showed a very rapid distribution outside the blood compartment. Similar results were observed when using nanocarriers together with a fast dissociation of 3 H-CE3F4 from nanocapsules simultaneously labeled with 14 C. Thus, essential preclinical information on CE3F4 fate has been obtained, as well as the impact of its formulation using lipid-based nanocarriers., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ambrisentan (AMB) is an orphan drug approved for oral administration that has been developed for the treatment of pulmonary arterial hypertension (PAH), a chronic and progressive pathophysiological state that might result in death if left untreated. Lipid-core nanocapsules (LNCs) are versatile nanoformulations capable of loading lipophilic drugs for topical, vaginal, oral, intravenous, pulmonary, and nasal administration. Our hypothesis was to load AMB into these nanocapsules (LNC amb ) and test their effect on slowing or reducing the progression of monocrotaline-induced PAH in a rat model, upon oral administration. LNC amb displayed a unimodal distribution of diameters (around 200 nm), negative zeta potential (-11.5 mV), high encapsulation efficiency (78%), spherical shape, and sustained drug release (50-60% in 24 h). The in vivo pharmacodynamic effect of the LNC amb group was evaluated by observing the echocardiography, hemodynamic, morphometric, and histological data, which showed a significant decrease in PAH in this group, as compared to the control group (AMB solution ). LNC amb showed the benefit of reversing systolic dysfunction and preventing vascular remodeling with greater efficacy than that observed in the control group. The originality and contribution of our work reveal the promising value of this nanoformulation as a novel therapeutic strategy for PAH treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

[Display omitted] Alzheimer's disease (AD) is a neurodegenerative disorder and the most relevant form of dementia affecting people worldwide. AD was reported to be associated with increased oxidative stress ending up with neuronal damage. 18β-Glycyrrhetinic acid (GA), triterpenoid aglycone of glycyrrhizin, was reported for its powerful antioxidant activities. However, its high molecular weight and lipophilicity are two major obstacles that limit its use and cause very low brain bioavailability. The aim of the present study was to formulate the GA in lipid nanocapsules (LNCs) for enhanced nose-to-brain delivery, as well as to elucidate its potential neuroprotective effect in AD. The optimized GA-loaded LNCs exhibited nanometric size range, good stability over 6 months, sustained drug release over 24 h and high steady state flux and permeability coefficient across nasal mucosa over 8 h. In-vivo studies were conducted on five groups; control, scopolamine (SCOP)-treated, SCOP + GA-LNCs, SCOP + oral GA suspension, and SCOP + intranasal GA suspension groups. Intranasal administration of GA-LNCs, at a reduced dose of 1 mg/kg, improved scopolamine-induced memory impairment in rats evidenced by behavioral testing, histological examination, and oxidative stress markers; catalase and superoxide dismutase. Collectively, GA-loaded LNCs (with 50 times lower dose) may provide a promising remedy for AD patients worldwide. [ABSTRACT FROM AUTHOR]

[Display omitted] Benznidazole, a poorly soluble in water drug, is the first-line medication for the treatment of Chagas disease, but long treatment periods at high dosages cause several adverse effects with insufficient activity in the chronic phase. According to these facts, there is a serious need for novel benznidazole formulations for improving the chemotherapy of Chagas disease. Thus, this work aimed to incorporate benznidazole into lipid nanocapsules for improving its solubility, dissolution rate in different media, and permeability. Lipid nanocapsules were prepared by the phase inversion technique and were fully characterized. Three formulations were obtained with a diameter of 30, 50, and 100 nm and monomodal size distribution with a low polydispersity index and almost neutral zeta potential. Drug encapsulation efficiency was between 83 and 92 % and the drug loading was between 0.66 and 1.04 %. Loaded formulations were stable under storage for one year at 4 °C. Lipid nanocapsules were found to protect benznidazole in simulated gastric fluid and provide a sustained release platform for the drug in a simulated intestinal fluid containing pancreatic enzymes. The small size and the almost neutral surface charge of these lipid nanocarriers improved their penetration through mucus and such formulations showed a reduced chemical interaction with gastric mucin glycoproteins. LNCs. The incorporation of benznidazole in lipid nanocapsules improved the drug permeability across intestinal epithelium by 10-fold compared with the non-encapsulated drug while the exposure of the cell monolayers to these nanoformulations did not affect the integrity of the epithelium. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lipid nanocapsules (LNCs) were tailored for indomethacin, diclofenac or caffeine dermal and/or transdermal delivery. • LNCs are able to encapsulate indomethacin and diclofenac with greater than 98 % efficiency. Caffeine is not encapsulated inside the lipid core. • FTIR confirmed the incorporation (or lack thereof) of the respective drug in lipid nanoparticles. • Ex vivo topical application of all studied drugs in LNCs is more effective than application of other conventional formulations. The transdermal application of actives offers numerous advantages over other conventional routes. Namely, a stable level of drugs in the bloodstream and reduced side effects are the argument for topical administration. Unfortunately, the exceptional skin barrier and unsuitable physico-chemical properties of drugs are the limiting factors for the transdermal passage. It is possible to overcome this by incorporating the drug into nano-carriers to enhance its permeation through the skin barrier. For this purpose, we prepared lipid nanocapsules (LNCs) to modulate skin passage of three pharmaceutically important drugs – indomethacin (IND), diclofenac sodium (DF) and caffeine (CF). We present a stable system prepared by the phase inversion temperature method with particle size under 100 nm and PDI < 0.1 with great encapsulation efficiency for indomethacin and diclofenac. By FTIR it was possible to confirm (for IND and DF) or disprove (in case of CF) the incorporation of a drug into the LNCs. By ex vivo permeation experiments on porcine skin, we confirmed the superior effect of the LNCs on the APIs skin passage. The drug permeated through the skin with higher intensity when delivered from LNCs compared to other standard formulations. We show that lipid nanocapsules play an important role in enhanced topical application of actives. [ABSTRACT FROM AUTHOR]