Protection of bovine mammary epithelial cells by a nanoemulsion of the medicinal herb Achyrocline satureioides (Lam.) DC and its capacity of permeation through mammary epithelium.

The low levels of toxicity and cytoprotective effect attributed to Achyrocline satureioides (Lam.) DC, a medicinal plant native to South America, are of interest for bovine mastitis therapy. This research paper reports the hypothesis that a nanoemulsion of macela extract (Achyrocline satureioides) exerts protective effects on bovine mammary alveolar cells -T (MAC-T) and increases the permeation of flavonoid compounds through mammary epithelium. Extract-loaded nanoemulsions (2.5 mg/ml) (NE-ML) (n = 4) were prepared using high-pressure homogenization with varying concentrations of flaxseed oil and Tween 80. Permeation and retention of free and nanoencapsulated quercetin, 3-O-methylquercetin and luteolin were performed on mammary glandular epithelium using Franz diffusion cells. The cell viability was evaluated on mammary epithelial cells (MAC-T lineage) using the MTT method (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) after exposure to loaded and blank nanoemulsions (NE-ML and NE-BL). Necrotic or apoptotic cell death was evaluated by flow cytometry after exposure to nanoemulsions (NE-ML and NE-BL). Subsequently, the cell death was assessed by previously treating MAC-T cells with NE-ML for 23 h, followed by exposure to H2O2 (2 mM) for 1 h. Higher permeation of quercetin and 3-O-methylquercetin in NE-ML was found compared to that of free extract with a final permeated amount of 50.7 ± 3.2 and 111.2 ± 0.6 µg/cm2 compared to 35.0 ± 0.6 and 48.9 ± 1.2, respectively. For NE-BL, the IC50 was at least 1.3% (v/v), while for the NE-ML, it was at least 2.6% (v/v). After exposure to NE-ML (5 and 1.2%, v/v), the percentage of apoptotic cells was reduced (±30%). For the H2O2 assay, the percentage of cells in necrosis was reduced by 40% after exposure to NE-ML1% (v/v) + H2O2 2 mM. The protective effects and increased permeation of macela nanoemulsion make this a promising new candidate for bovine mastitis therapy.

The nanotechnological approach for nasal delivery of peptide drugs: a comprehensive review.

This review gathers recent studies, patents, and clinical trials involving the nasal administration of peptide drugs to supply a panorama of developing nanomedicine advances in this field. Peptide drugs have been featured in the pharmaceutical market, due to their high efficacy, biological activity, and low immunogenicity. Pharmaceutical industries need technology to circumvent issues relating to peptide stability and bioavailability. The oral route offers very harsh and unfavourable conditions for peptide administration, while the parenteral route is inconvenient and risky for patients. Nasal administration is an attractive alternative, mainly when associated with nanotechnological approaches. Nanomedicines may improve the nasal administration of peptide drugs by providing protection for the macromolecules from enzymes while also increasing their time of retention and permeability in the nasal mucosa. Nanomedicines for nasal administration containing peptide drugs have been acclaimed for both prevention, and treatment, of infections, including the pandemic COVID-19, cancers, metabolic and neurodegenerative diseases.

Assessing the In Vitro Drug Release from Lipid-Core Nanocapsules: a New Strategy Combining Dialysis Sac and a Continuous-Flow System.

The in vitro assessment of drug release from polymeric nanocapsules suspensions is one of the most studied parameters in the development of drug-loaded nanoparticles. Nevertheless, official methods for the evaluation of drug release from submicrometric carriers are not available. In this work, a new approach to assess the in vitro drug release profile from drug-loaded lipid-core nanocapsules (LNC) was proposed. A continuous-flow system (open system) was designed to evaluate the in vitro drug release profiles from different LNC formulations containing prednisolone or clobetasol propionate (LNC-CP) as drug model (LNC-PD) using a homemade apparatus. The release medium was constantly renewed throughout the experiment. A dialysis bag containing 5 mL of formulation (0.5 mg mL(-1)) was maintained inside the apparatus, under magnetic stirring and controlled temperature (37°C). In parallel, studies based on the conventional dialysis sac technique (closed system) were performed. It was possible to discriminate the in vitro drug release profile of different formulations using the open system. The proposed strategy improved the sink condition, by constantly renewing the release medium, thus maintaining the drug concentration farther from the saturated concentration in the release medium. Moreover, problems due to sampling errors can be easily overcome using this semi-automated system, since the collection is done automatically without interference from the analyst. The system proposed in this paper brings important methodological and analytical advantages, becoming a promising prototype semi-automated apparatus for performing in vitro drug release studies from drug-loaded lipid-core nanocapsules and other related nanoparticle drug delivery systems.

Intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions improves cognitive impairments in a mouse model of Alzheimer's disease.

Nasal delivery has emerged as a non-invasive route to administer drugs for brain delivery. In particular, polyelectrolyte complexes-based nanocarriers have been demonstrated to be advantageous for nasal delivery of peptide drugs and vaccines. Pramlintide (Pram) is a peptide that emerges as a novel neuroprotective strategy to modify the pathogenesis of Alzheimer's disease (AD). In this study, we examined the effects of the intranasal administration of dextran-pramlintide polyelectrolyte complex-coated nanoemulsions (PEC-NEDexS/Pram) in an experimental model of AD induced by intracerebroventricular (i.c.v.) infusion of amyloid-beta (Aß1-42) peptide in mice. PEC-NEDexS/Pram displayed droplet size lower than 200 nm and a negatively charged surface. The locomotor activity of the animals was not affected by the i.c.v. Aß1-42 injection or Pram treatment. On the other hand, the intranasal administration of PEC-NEDexS/Pram at a dose of 100 µg/day for 14 consecutive days restored the impairment induced by Aß1-42 injection in the discriminative learning and the short-term spatial reference memory of mice. However, Pram treatment did not alter the Aß1-42-induced anhedonic behavior, oxidative stress parameters, or the pre-synaptic SNAP-25 and post-synaptic PSD-95 levels in the hippocampus and prefrontal cortex. These findings indicate cognitive-enhancing properties of intranasal Pram administration in an animal model of AD.