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In order to search for new approaches to treat glioma, intranasal administration has been proposed as an alternative route to deliver drugs into the brain. Among the drug ...alternatives, kaempferol (KPF) has been reported to induce glioma cell death. This study aimed to prepare nanoemulsions containing KPF with and without chitosan to investigate their potential for brain delivery following intranasal administration, and to evaluate their antitumor activity against glioma cells. KPF-loaded nanoemulsion (KPF-NE) and KPF-loaded mucoadhesive nanoemulsion (KPF-MNE) were prepared by high-pressure homogenization technique and were characterized for their globule size, zeta potential, drug content, pH, viscosity, mucoadhesive strength and morphology. KPF from KPF-MNE showed significantly higher permeation across the mucosa in ex vivo diffusion studies. Histopathological examination suggests both nanoemulsions to be safe for the nasal mucosa and able to preserve KPF antioxidant capability. KPF-MNE enhanced significantly the amount of drug into rat’s brain following intranasal administration (5- and 4.5-fold higher than free drug and KPF-NE, respectively). In addition, KPF-MNE reduced C6 glioma cell viability through induction of apoptosis to a greater extent than either free KPF or KPF-NE. The mucoadhesive nanoemulsion developed for intranasal administration may be a promising system for delivery to the brain, and KPF-MNE is a candidate for further antiglioma trials.
The poor water solubility of flavonoids represents the greatest challenge to increasing the oral bioavailability of these compounds. Nevertheless, several potential positive effects of flavonoids ...have been demonstrated by many studies and therefore much attention has been given to developing ways to improve solubility, such as solid dispersions (SD). However, there is no review evaluating the general impact of the use of SD on flavonoids. Thus, this review aims to present a detailed analysis of the current literature which used the SD approach to ameliorate the solubility, dissolution, and oral bioavailability parameters of flavonoids for use in future research. Most studies adopted the solvent evaporation method and polyvinylpyrrolidone was the most common carrier used. In general, the studies concluded that SD developed by different methods using different carriers are an excellent alternative to improve solubility, dissolution and significantly increase the oral bioavailability of subclasses of flavonoids.
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•Chitosan-coated RA nanoemulsion was successfully optimized using Box-Behnken design.•Mucoadhesive potential from chitosan-coated RA nanoemulsion was demonstrated.•Adequate ...physicochemical characteristics and prolonged RA release was also observed.•Long-lasting permeation and higher RA retention in porcine nasal mucosa was achieved.•Safety profile from chitosan-coated RA nanoemulsion was investigated in fibroblasts.
Mucoadhesive chitosan-coated nanoemulsions for rosmarinic acid (RA) nasal delivery were optimized. The optimum ratio between the formulation components that led to minimum droplet size and PDI, and maximal ζ-potential and RA content was obtained using Box-Behnken design (BBD). Optimized conditions were 8.5% oil phase (w/v), 3:10 lecithin to oil phase ratio (w/w), and 0.1% chitosan final concentration (w/v). Physicochemical characterization, mucoadhesion measurement, in vitro release and permeation/retention were performed. Optimized chitosan-coated RA nanoemulsions presented adequate physicochemical characteristics, high mucoadhesive potential, prolonged drug release, and long-lasting permeation time with a higher RA penetration/retention through porcine nasal mucosa. Cell viability and death by necrosis in fibroblasts cells were also evaluated to investigate the formulations safety. Formulations did not induce cytotoxicity following 24 h (3.125–50 μM) or 48 h (3.125–25 μM) of treatments. Overall results demonstrated that optimized chitosan-coated nanoemulsion showed to be a suitable carrier for RA nasal delivery aiming neuroprotective therapies.
The largest organ of the body provides the main challenge for the transdermal delivery of lipophilic or high molecular weight drugs. To cross the main barrier of the skin, the stratum corneum, many ...techniques have been developed and improved. In the last 20 years, the association of microneedles with nanostructured systems has gained prominence for its versatility and for enabling targeted drug delivery. Currently, the combination of these mechanisms is pointed to as an emerging technology; however, some gaps need to be answered to transcend the development of these devices from the laboratory scale to the pharmaceutical market. It is known that the lack of regulatory guidelines for quality control is a hindrance to market conquest. In this context, this study undertakes a scoping review of original papers concerning methods applied to evaluate both the quality and drug/protein delivery of dissolving and hydrogel-forming microneedles developed in association with nanostructured systems.
Neurodegenerative disorders (ND) are characterized by slow and progressive neuronal dysfunction induced by the degeneration of neuronal cells in the central nervous system (CNS). Recently, the ...neuroprotective effects of natural compounds with anti-inflammatory and antioxidant activities has been clearly demonstrated. This appears to be an attractive therapeutic approach for ND, particularly regarding the use of polyphenols. In this review, we present an overview of the neuroprotective potential of rosmarinic acid (RA) and discuss the use of nanotechnology as a novel approach to treating ND. RA presents a variety of biological important activities, i.e. the modulation of pro-inflammatory cytokine expression, prevention of neurodegeneration and damage reduction. However, its poor bioavailability represents a limitation in terms of pharmacodynamics. In this sense, nanotechnology-based carriers could allow for the administration of higher but still safe amounts of RA, aiming for CNS delivery. Nasal administration could be a pleasant route for delivery to the CNS, as this represents a direct route to the CNS. With these advantages, RA-loaded nanotechnology-based therapy through the nasal route could be promising approach for the treatment of ND.
•RA exhibits anti-inflammatory and antioxidant activities.•RA exhibits neuroprotective potential for treating ND.•RA present poor oral bioavailability and permeability in CNS.•Nanotechnology-based therapy emerges as a promising strategy for RA.•RA nasal delivery could also be a pleasant route for CNS delivery.
Rosmarinic acid (RA) is a natural polyphenolic compound with a well-documented neuroprotective effect mainly associated with its anti-inflammatory and antioxidant activities. Recently, our research ...group developed and optimized chitosan-coated RA nanoemulsions (RA CNE) intended to be used for nasal delivery as a new potential neuroprotective therapy. In this sense, the present study aimed to evaluate the protective and/or therapeutic potential of RA CNE in inflammation/oxidative stress induced by LPS (1 μg mL
−1
) in rat astrocyte primary cultures. In summary, pre-treatment with RA CNE before exposure to LPS (protective protocol) reduced significantly the LPS-induced alterations in astrocyte cell viability, proliferation, and cell death by necrosis, which was not observed in therapeutic protocol. RA CNE protective protocol also enhanced anti-oxidative status by ~ 50% by decreasing oxygen reactive species production and nitric oxide levels and preventing total thiol content decrease. Finally, our results demonstrate the protective effect of RA CNE in migratory activation and GFAP expression of reactive astrocytes. Overall, our findings indicate for the first time the RA CNE glioprotective potential, associated with an increase in cell viability and proliferation, a preventive effect on cellular death by necrosis, migratory ability and hypertrophic reactive astrocytes, and the reparation of astrocyte redox state.
Graphical Abstract
Objectives
Natural sources with antioxidant activity, such as rosmarinic acid (RA), have been considered as an interesting approach for the development of new anti‐ageing skin products. In this ...context, this study aimed to develop hydrogels containing RA‐loaded nanoemulsions and evaluate the effect of the addition of Tween® 80 (a nonionic cosurfactant) in formulations intended to be used for topical application.
Methods
Physico‐chemical characterization, in‐vitro release and skin retention/permeation from hydrogels of RA‐loaded nanoemulsions (containing or not Tween® 80) were evaluated. The RA‐loaded nanoemulsion safety profiles were also investigated in keratinocytes (HaCaT cells).
Key findings
It was observed that all formulations presented adequate physico‐chemical characterization for topical application. Furthermore, the results also demonstrated that the presence of Tween® 80 decreased the droplet size and polydispersity index of nanoemulsions and hydrogels. An extended RA release was noted for the hydrogels. However, when comparing the hydrogels, a positive effect of the presence of Tween® 80 on RA retention/permeation in total skin was seen. The RA‐loaded nanoemulsion safety profiles demonstrated a good tolerability (3.125–100 μm) in HaCaT cells.
Conclusions
The overall results demonstrated that the formulations developed in this study can be considered as a suitable carrier for RA in a topical application targeting new anti‐ageing skin care products.
The use of nanocellulose in pharmaceutics is a trend that has emerged in recent years. Its inherently good mechanical properties, compared to different materials, such as its high tensile strength, ...high elastic modulus and high porosity, as well as its renewability and biodegradability are driving nanocellulose's industrial use and innovations. In this sense, this study aims to conduct a search of patents from 2011 to 2023, involving applications of nanocellulose in pharmaceuticals. A patent search was carried out, employing three different patent databases: Patentscope from World Intellectual Property Organization (WIPO); Espacenet; and LENS.ORG. Patents were separated into two main groups, (i) nanocellulose (NC) comprising all its variations and (ii) bacterial nanocellulose (BNC), and classified into five major areas, according to their application. A total of 215 documents was retrieved, of which 179 were referred to the NC group and 36 to the BNC group. The NC group depicted 49.7%, 15.6%, 16.2%, 8.9% and 9.5% of patents as belonging to design and manufacturing, cell culture systems, drug delivery, wound healing and tissue engineering clusters, respectively. The BNC group classified 44.5% of patents as design and manufacturing and 30.6% as drug delivery, as well as 5.6% and 19.4% of patents as wound healing and tissue engineering, respectively. In conclusion, this work compiled and classified patents addressing exclusively the use of nanocellulose in pharmaceuticals, providing information on its current status and trending advancements, considering environmental responsibility and sustainability in materials and products development for a greener upcoming future.
The essential oil extracted from the leaves of Piper aduncum, an aromatic plant from the Amazon region, is rich in dillapiole and presents anti-inflammatory activity. In this study, nanoemulsions ...(NE) and nanostructured lipid carriers (NLC), which are biocompatible nanostructured systems of a lipid nature, were prepared by high-pressure homogenization for the yet unexplored skin delivery of dillapiole. The addition of hydroxyethylcellulose produced hydrogel-thickened NE or NLC in view to improving the viscosity and skin adherence of the nanoformulations. Formulations were characterized with respect to dillapiole content, droplet size, polydispersity index, zeta potential, morphology, rheological behavior, bioadhesion, skin permeation profile, and in vitro irritancy (HET-CAM). The formulations developed presented spherical, homogeneous nanometric particle size (around 130 nm), narrow polydispersity index (<0.3), and negative zeta potential (around −40 mV). Dillapiole content was slightly lower in NLC compared to NE since the production process involves heating. The hydrogels containing nanocarriers showed pseudoplastic behavior with bioadhesive characteristics. The developed formulations exhibited a controlled release profile, dillapiole delivery up to the dermis, the layer of interest for anti-inflammatory potential, and low irritant potential in the chorioallantoic membrane (HET-CAM). Both hydrogels-thickened NE and NLC seemed to be promising formulations for skin delivery of Piper aduncum essential oil.
Aniba canelilla (Kunth) Mez is an aromatic tree from Amazon region whose essential oil presents 1-nitro-2-phenylethane (NP) and methyleugenol (ME) as major compounds. Several properties are ...attributed to Aniba canelilla essential oil (ACEO), such as antifungal. Onychomycoses are fungal nail infections that require novel therapeutic alternatives, especially topical ones. However, to ensure the success of topical therapy, the active compound should be able to penetrate/permeate the nail plate, which is challenging due to the highly keratinized composition of this structure. Thus, the aims of this article were to develop, validate and apply a high-performance liquid chromatography method (HPLC-UV) to quantify NP and ME in porcine hoof extract (PHE) and receptor fluid (RF) during in vitro permeation/retention studies in nail model, for which porcine hoof membranes were used. For method development, two Designs of Experiment (DoE) were adopted: 2
Full Factorial and Box-Behnken. Retention times of 5.65 and 7.49 min were achieved for NP and ME, respectively. The method was full validated for NP and ME quantification in receptor fluid, in accordance with the recommended parameters by ICH Q2(R1) Guideline. In addition, the method was full validated for NP and ME quantification in porcine hoof extract, considering the parameters and criteria of ICH M10 Guideline. In vitro permeation/retention studies were carried out in nail model, and promising results were obtained. NP reached the receptor fluid in the order of 441.1 ± 92.1 µg/cm
at 72 h. The amount of NP and ME retained into porcine hoof membrane was 1272.6 ± 225.7 µg/cm
and 84.7 ± 20.4 µg/cm
, respectively, at 72 h. Our findings open perspective to develop topical formulations containing ACEO as active compound aiming the management of onychomycosis.
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