Introduction: Nutraceuticals, up today, do not have a specific definition distinct from those of other food-derived categories, e.g. food supplements, herbal products, pre and probiotics, functiona...

From pharmaceuticals to nutraceuticals: bridging disease prevention and management.

Traditionally, Andrographis paniculata has been used as an herbal remedy for lung infection treatments. Its leaves contain a diterpenoid labdane called andrographolide responsible for a wide range of biological activities such as antioxidant, anti-inflammatory, and anti-cancer properties. This manuscript is a brief review of the antioxidant mechanisms and the regulation of the Nrf2 (nuclear factor (erythroid-derived 2)-like 2) signaling pathway by andrographolide.

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Andrographolide, a Natural Antioxidant: An Update.

In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.

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Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases.

Two novel nanomicellar formulations were developed to improve the poor aqueous solubility and the oral absorption of silymarin. Polymeric nanomicelles made of Soluplus and mixed nanomicelles combining Soluplus with d-α-tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS) were prepared using the thin film method. Physicochemical parameters were investigated, in particular the average diameter, the homogeneity (expressed as polydispersity index), the zeta potential, the morphology, the encapsulation efficiency, the drug loading, the critical micellar concentration and the cloud point. The sizes of ~60 nm, the narrow size distribution (polydispersity index ≤0.1) and the encapsulation efficiency >92% indicated the high affinity between silymarin and the core of the nanomicelles. Solubility studies demonstrated that the solubility of silymarin increased by ~6-fold when loaded into nanomicelles. Furthermore, the physical and chemical parameters of SLM-loaded formulations stored at room temperature and in refrigerated conditions (4 °C) were monitored over three months. In vitro stability and release studies in media miming the physiological conditions were also performed. In addition, both formulations did not alter the antioxidant properties of silymarin as evidenced by the 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) assay. The potential of the nanomicelles to increase the intestinal absorption of silymarin was firstly investigated by the parallel artificial membrane permeability assay. Subsequently, transport studies employing Caco-2 cell line demonstrated that mixed nanomicelles statistically enhanced the permeability of silymarin compared to polymeric nanomicelles and unformulated extract. Finally, the uptake studies indicated that both nanomicellar formulations entered into Caco-2 cells via energy-dependent mechanisms.

https://www.mdpi.com/1420-3049/24/9/1688/pdf

Formulation of Nanomicelles to Improve the Solubility and the Oral Absorption of Silymarin.

Pickering emulsions stabilized by colloidal surfactants: Role of solid particles

Natural products are fascinating molecules in drug discovery for their exciting structure variability and also for their interaction with various targets. Drugs multi-targeting effect represents a more realistic approach to develop successful medications for many diseases. However, besides a large number of successful in vitro and in vivo studies, most of the clinical trials fail. This is generally related to the scarce water solubility, low lipophilicity and inappropriate molecular size of natural compounds, which undergo structural instability in biological milieu, rapid clearance and high metabolic rate. Additionally, some molecules are destroyed in gastric juice or suffer to a massive pre-systemic metabolism in the liver, when administered orally, limiting their clinical use. A reduced bioavailability can also be linked to drug distribution/accumulation in non-targeted tissues and organs that increase the side effects lowering the therapeutic efficacy and patient compliance. Nanomedicine represents a favourable tool to increase bioavailability and activities of natural products. Generally, nanovectors provide a large surface area and can overcome anatomic barriers. Each nanovector has its own advantages, disadvantages, and characteristics. In this review, different nanocarriers made of compounds which are Generally Recognized As Safe (GRAS) for the delivery of natural products, marketed as food supplements and medicines are reported.

Nanocarriers: A Successful Tool to Increase Solubility, Stability and Optimise Bioefficacy of Natural Constituents.

Andrographolide Loaded in Micro- and Nano-Formulations: Improved Bioavailability, Target-Tissue Distribution, and Efficacy of the “King of Bitters”



The skin-PAMPA test is a quick and relatively deep tool in the early stages of
drug discovery and formulation of dermal and transdermal delivery systems.



This study focused on the application of the skin-PAMPA test to evaluate the permeation of
Resveratrol (RSV) and also of two formulations, Liposomes (LP) and Nanostructured Lipid Carriers
(NLC), prepared to improve RSV topical delivery.



LP and NLC were physically and chemically characterized. Stability and in vitro release
studies were also assessed in different pH media. The release results were applied to define the kinetic
and mechanism of RSV release from the LP and NLC formulations. In vitro permeability was estimated
through the skin-PAMPA and the antioxidant capacity was evaluated by DPPH test.



Nanoparticles have a spherical shape, dimensions suitable for skin application, and narrow size
distribution. Encapsulation efficiency was 96.5% ± 2.1 for LP and 86.0% ± 2.4 for NLC. The formulations
increased RSV solubility. Nanoparticles showed excellent physical and chemical stability during
storage at 4°C for two months. In vitro release studies were performed at pH 5.5 and 7.4. The nanoparticles
achieved a prolonged release of RSV. Skin-PAMPA proved an increased cutaneous permeability
of RSV when loaded into LP or NLC. Both formulations maintained the antioxidant capacity of RSV,
as evidenced by DPPH test.



LP and NLC could be applied as drug delivery systems suitable for the topical delivery of
the RSV. Skin-PAMPA has proved to be an effective tool for studying the permeability not only of the
RSV but also of its formulations.


Marta Casamonti

Papers

Nanocarriers: A Successful Tool to Increase Solubility, Stability and Optimise Bioefficacy of Natural Constituents.

Andrographolide Loaded in Micro- and Nano-Formulations: Improved Bioavailability, Target-Tissue Distribution, and Efficacy of the “King of Bitters”

Evaluation of Skin Permeability of Resveratrol Loaded Liposomes and Nanostructured Lipid Carriers using a Skin Mimic Artificial Membrane (skin-PAMPA)