Nanoemulsion for improving solubility and permeability of Vitex agnus-castus extract: formulation and in vitro evaluation using PAMPA and Caco-2 approaches

The purpose of this study was to develop new formulation for an improved oral delivery of Vitex agnus-castus (VAC) extract. After the optimization and validation of analytical method for quali-quantitative characterization of extract, nanoemulsion (NE) was selected as lipid-based nanocarrier. The composition of extract-loaded NE resulted in triacetin as oil phase, labrasol as surfactant, cremophor EL as co-surfactant and water. NE contains until 60 mg/mL of extract. It was characterized by DLS and TEM analyses and its droplets appear dark with an average diameter of 11.82 ± 0.125 nm and a polydispersity index (PdI) of 0.117 ± 0.019. The aqueous solubility of the extract was improved about 10 times: the extract is completely soluble in the NE at the concentration of 60 mg/mL, while its solubility in water results less than 6 mg. The passive intestinal permeation was tested by using parallel artificial membrane permeation assay (PAMPA) and the permeation across Caco-2 cells after preliminary cytotoxicity studies were also evaluated. NE shows a good solubilizing effect of the constituents of the extract, compared with aqueous solution. The total amount of constituents permeated from NE to acceptor compartment is greater than that permeated from saturated aqueous solution. Caco-2 test confirmed PAMPA results and they revealed that NE was successful in increasing the permeation of VAC extract. This formulation could improve oral bioavailability of extract due to enhanced solubility and permeability of phytocomplex

Plants Extracts Loaded in Nanocarriers: An Emergent Formulating Approach:

Over the millennia, plants have represented for Humankind the main source of food, but also a vast resource to maintain health, for prophylactic properties or to cure human and animal diseases. Presently, between 65 and 80% of populations in developing countries use medicinal plants as therapeutic remedies for their primary healthcare and in Europe and USA there is an increasing demand of botanical products both on the form of food supplements and herbal medicinal products. Botanicals on the market are mainly based on traditional (infusions or decoctions), conventional (using organic solvents) and innovative (supercritical CO2 or subcritical water) extracts but there is an increasing demand of essential oils for aromatherapy. Conversely, the clinical use of many extracts is limited due to the need of repeated administrations or high doses because of low hydrophilicity and intrinsic dissolution rate(s), or physical/ chemical instability. Other limits are low absorption, poor pharmacokinetics and bioavailability, scarce biodistribution, first pass metabolism, trivial penetration and accumulation in the organs of the body. In the case of essential oils, the high volatility and instability are further limitations. Nowadays, the design and production of appropriate drug delivery systems, in particular nanosized ones (between 50 and 300 nm), have already entered into clinical use and can offer an advanced approach to optimized the therapeutic efficacy of extracts and essential oils. A successful drug carrier system should have optimal drug loading and release properties, a long shelf life, and exert a much higher therapeutic efficacy as well as lower side effects. Polymeric nanoparticles and lipid based-nanocarriers including micelles, vesicles, nanocochleates, micro- and nanoemulsions represent successful examples of extract nanoformulations overcoming these limitations. This review reports on some paradigmatic success stories of extract and EO nanoformulations with remarkable advantages over conventional formulations, which include increase of solubility, stability, permeation and bioavailability, sustained delivery. Paradigmatic examples include formulations of extracts from Vitex agnus-castus, Sylibum marianum, Phyllanthus amarus, Ginkgo biloba, Panax notoginseng, Hypericum perforatum and thyme essential oil

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

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

Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration

Posidonia oceanica (L.) Delile is a marine plant endemic of Mediterranean Sea endowed with interesting bioactivities. The hydroalcholic extract of P. oceanica leaves (POE), rich in polyphenols and carbohydrates, has been shown to inhibit human cancer cell migration. Neuroblastoma is a common childhood extracranial solid tumor with high rate of invasiveness. Novel therapeutics loaded into nanocarriers may be used to target the migratory and metastatic ability of neuroblastoma. Our goal was to improve both the aqueous solubility of POE and its inhibitory effect on cancer cell migration. Methods: Chitosan nanoparticles (NP) and Soluplus polymeric micelles (PM) loaded with POE have been developed. Nanoformulations were chemically and physically defined and characterized. In vitro release studies were also performed. Finally, the inhibitory effect of both nanoformulations was tested on SH-SY5Y cell migration by wound healing assay and compared to that of unformulated POE. Results: Both nanoformulations showed excellent physical and chemical stability during storage, and enhanced the solubility of POE. PM-POE improved the inhibitory effect of POE on cell migration probably due to the high encapsulation efficiency and the prolonged release of the extract. Conclusions: For the first time, a phytocomplex of marine origin, i.e., P. oceanica extract, has enhanced in terms of acqueous solubility and bioactivity once encapsulated inside nanomicelles