Lipid-core nanocapsules containing simvastatin improve the cognitive impairment induced by obesity and hypercholesterolemia in adult rats.

The development of cognitive impairment may be related to high levels of plasma cholesterol and obesity. Simvastatin (SV) and lovastatin (LV) are drugs that can potentially be used for the treatment of cognitive deficit. This study aimed to develop and characterize lipid-core nanocapsules (LNC) containing SV (SV-LNC) or LV (LV-LNC), evaluating the effects of SV-LNC in an animal model of cognitive deficit. The formulations SV-LNC and LV-LNC presented a particle average size around 200 nm, a low-polydispersity index, and negative zeta potential. Analysis of differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that there is no reaction among LNC components: LV was crystallized in the suspensions, and SV was molecularly dispersed. The encapsulation efficiency of the SV was high (98.9 ± 1.4%), while that of the LV was low (21.5 ± 1.5%).Based on these results, SV-LNC was used in the preclinical studies. Animals fed with a hyperlipidic diet (HD) developed obesity, hypercholesterolemia, and cognitive impairment, which was corroborated by the brain lesions indicated by histological analysis of some of the animals that received the high-fat diet. We observed that free simvastatin (CS3) was able to reduce the enzymatic activity of pyruvate kinase, an important enzyme for brain energy homeostasis, without affecting the memory of the animals that received a standard diet. However, it failed to improve the cognitive damage caused by a diet high in cholesterol and saturated fats. On the other hand, when simvastatin is "camouflaged" in the lipid-core nanocapsules (HNS3), this cognitive impairment improves. Thus, SV-LNC is a promising alternative therapy for the treatment of cognitive impairment.

Amazonia Products in Novel Lipid Nanoparticles for Fucoxanthin Encapsulation.

Lipid nanoparticles (LNs) are traditional systems able to effectively increase skin hydration. However, due to its reduced viscosity, LNs suspensions are less attractive for skin administration. To overcome this disadvantage, the LN were incorporated in the semi-solid formulation is easy manipulation. This study demonstrated that it is possible to obtain novel LN-loaded fucoxanthin (LN-FUCO) for topical administration containing a combination of bacuri butter and tucumã oil prepared by high shear homogenization for improved stability. The particle size was found to be 243.0 nm and the entrapment efficiency up to 98% of FUCO was incorporated and achieved the suitability of formula. The LN-FUCO hydrogel characteristics of slight acidity, drug content near 100%, and nanometric mean size assure to this formulation high compatibility to dermal application. Photostability assay by UVA, LN-FUCO, and LN-FUCO hydrogel improved photostability and conferred greater protection against FUCO degradation. The results obtained from in vitro skin permeation studies presented a significant difference between LN-FUCO hydrogel and FUCO (p < 0.05), with no detection of the drug in the receptor medium. Therefore, high shear homogenization is demonstrated to be a simple, available, and effective method to prepare high-quality LN-FUCO hydrogel for topical application.

Lipid-core nanocapsules are an alternative to the pulmonary delivery and to increase the stability of statins.

Aims: Lipid-core nanocapsules (LNCs) loaded with simvastatin (SV, SV-LNC) or lovastatin (LV, LV-LNC) were formulated for pulmonary administration. Methods: The LNC suspensions were characterized physicochemically, their stability was evaluated, and drug delivery by the pulmonary route was tested in vitro. Results: The loaded LNCs had a particle size close to 200 nm, a low polydispersity index, and a zeta potential around -20 mV. The encapsulation efficiency was high for SV (99.21 ± 0.7%) but low for LV (20.34 ± 1.2%). SV release from nanocapsules was slower than it was from SV in solution, with a monoexponential release profile, and the drug emitted and aerosol output rate was higher for SV-LNCs (1.58 µg/s) than for SV in suspension (0.54 µg/s). Conclusions: SV-LNCs had a median aerodynamic diameter of 3.51 µm and a highly respirable fraction (61.9%), indicating that nanoparticles are a suitable system for efficient delivery of simvastatin to the lung.

Microbial transformation of ambrisentan to its glycosides by Cunninghamella elegans.

The purpose of this paper is to describe the glycosylation of ambrisentan (AMB) by cultures of Cunninghamella elegans ATCC 9245. AMB is an endothelin receptor antagonist, which is used to treat pulmonary arterial hypertension. Filamentous fungi are morphologically complex and may exhibit different forms depending on the species and the nature of the culture medium. A biotransformation study was conducted to investigate the ability of C. elegans to metabolize AMB. Parameters were optimized by testing on different culture media and concentrations, pH, drug concentration, static and shaking conditions. Ambrisentan's metabolite, obtained after 240 h of incubation as a result of glycosylation pathway, was separated by HPLC and determined by high-resolution mass spectrometry. The method showed linearity over 300-1000 µg mL-1 (r = 0.998). Accuracy, precision, robustness and stability studies agree with international guidelines. Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and used little solvent.

In vitro evaluation of cutaneous penetration of acyclovir from semisolid commercial formulations and relation with its effective antiviral concentration

ABSTRACT The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV) into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic) and different (similar) excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC50 (inhibitory concentration required to reduce viral replication by 50%). According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products.

Simultaneous separation and sensitive detection of naringin and naringenin in nanoparticles by chromatographic method indicating stability and photodegradation kinetics.

A simple, sensitive, precise and linear method by liquid chromatography was established for simultaneous determination and quantification of naringin and naringenin in polymeric nanoparticles. The method results in excellent separation in <11 min and with a peak purity of both flavonoids. The analyses were performed using a C18 column (4.6 × 150 mm, 5 µm), at a 1 mL/min flow rate. The mobile phase consisted of a gradient of acetonitrile-water (pH 4.0; v/v) at a temperature of 25°C. The nanoparticles were prepared according to the method of interfacial deposition of a pre-formed polymer. The method were validated in compliance with guidelines, and was found to be linear in the 1-40 µg/mL concentration range for both naringin and naringenin (r > 0.99). Repeatability was determined at three concentration levels, obtaining an RSD (%) <0.9%, and the accuracy of the method was >98%. The photodegradation kinetics was determined for naringin; the coefficient that best represents degradation was of first order and naringenin presented a zero-order kinetics. To our knowledge, a rapid and sensitive method for naringin and naringenin in polymeric nanoparticles has not been published elsewhere and this method is applicable to simultaneous evaluation of flavonoids.