Topical Administration of Terpenes Encapsulated in Nanostructured Lipid-Based Systems.

Terpenes are a group of phytocompounds that have been used in medicine for decades owing to their significant role in human health. So far, they have been examined for therapeutic purposes as antibacterial, anti-inflammatory, antitumoral agents, and the clinical potential of this class of compounds has been increasing continuously as a source of pharmacologically interesting agents also in relation to topical administration. Major difficulties in achieving sustained delivery of terpenes to the skin are connected with their low solubility and stability, as well as poor cell penetration. In order to overcome these disadvantages, new delivery technologies based on nanostructures are proposed to improve bioavailability and allow controlled release. This review highlights the potential properties of terpenes loaded in several types of lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers) used to overcome free terpenes' form limitations and potentiate their therapeutic properties for topical administration.

Ursolic Acid Formulations Effectively Induce Apoptosis and Limit Inflammation in the Psoriasis Models In Vitro.

Psoriasis, a prevalent inflammatory skin disorder affecting a significant percentage of the global population, poses challenges in its management, necessitating the exploration of novel cost-effective and widely accessible therapeutic options. This study investigates the potential of ursolic acid (UA), a triterpenoid known for its anti-inflammatory and pro-apoptotic properties, in addressing psoriasis-related inflammation and keratinocyte hyperproliferation. The research involved in vitro models employing skin and immune cells to assess the effects of UA on psoriasis-associated inflammation. The presented research demonstrates the limiting effects of UA on IL-6 and IL-8 production in response to the inflammatory stimuli and limiting effects on the expression of psoriatic biomarkers S100A7, S100A8, and S100A9. Further, the study reveals promising outcomes, demonstrating UA's ability to mitigate inflammatory responses and hyperproliferation of keratinocytes by the induction of non-inflammatory apoptosis, as well as a lack of the negative influence on other cell types, including immune cells. Considering the limitations of UA's poor solubility, hybrid systems were designed to enhance its bioavailability and developed as hybrid nano-emulsion and bi-gel topical systems to enhance bioavailability and effectiveness of UA. One of them in particular-bi-gel-demonstrated high effectiveness in limiting the pathological response of keratinocytes to pro-psoriatic stimulation; this was even more prominent than with ursolic acid alone. Our results indicate that topical formulations of ursolic acid exhibit desirable anti-inflammatory activity in vitro and may be further employed for topical psoriasis treatment.

Topical Formulations Based on Ursolic Acid-Loaded Nanoemulgel with Potential Application in Psoriasis Treatment.

Psoriasis is a chronic disorder that causes a rash with itchy, scaly patches. It affects nearly 2-5% of the worldwide population and has a negative effect on patient quality of life. A variety of therapeutic approaches, e.g., glucocorticoid topical therapy, have shown limited efficacy with systemic adverse reactions. Therefore, novel therapeutic agents and physicochemical formulations are in constant need and should be obtained and tested in terms of effectiveness and minimization of side effects. For that reason, the aim of our study was to design and obtain various hybrid systems, nanoemulgel-macroemulsion and nanoemulgel-oleogel (bigel), as vehicles for ursolic acid (UA) and to verify their potential as topical formulations used in psoriasis treatment. Obtained topical formulations were characterized by conducting morphological, rheological, texture, and stability analysis. To determine the safety and effectiveness of the prepared ursolic acid carriers, in vitro studies on human keratinocyte cell-like HaCaT cells were performed with cytotoxicity analysis for individual components and each formulation. Moreover, a kinetic study of ursolic acid release from the obtained systems was conducted. All of the studied UA-loaded systems were well tolerated by keratinocyte cells and had suitable pH values and stability over time. The obtained formulations exhibit an apparent viscosity, ensuring the appropriate time of contact with the skin, ease of spreading, soft consistency, and adherence to the skin, which was confirmed by texture tests. The release of ursolic acid from each of the formulations is followed by a slow, controlled release according to the Korsmeyer-Peppas and Higuchi models. The elaborated systems could be considered suitable vehicles to deliver triterpene to psoriatic skin.

Preparation and Characterization of Water-Based Nano-Perfumes.

The application of nanoemulsions as a novel delivery system for lipophilic materials, such as essential oils, flavors, and fragrances is one of the growing technologies used in cosmetic, pharmaceutical, and food industries. Their characteristic properties, like small droplet size with high interfacial area, transparent or semi-transparent appearance, low viscosity, and high kinetic stability, make them a perfect vehicle for fragrances, in the perfume industry. They could be a great alternative to water-based perfumes, without alcohol, and solve problems related to the oxidation and low bioavailability of fragrances with other non-alcoholic vehicles of perfumes like pomades or gels. The aim of our study was to develop stable Oil-in-Water (O/W) nanoemulsions that are compatible with selected fragrance compositions, without ethanol, polyols, and ionic surfactants, and to study their physicochemical, microbiological, and dermatological properties. The nano-perfume systems were obtained with a low-energy (Phase Inversion Composition; PIC) and with a high-energy (ultrasound, US) method, taking into account the possibility of moving from the laboratory scale to an industrial scale. The optimized nano-perfume formulations, prepared with different methods, yielded the same physicochemical properties (stability, medium droplet size of the inner phase, polydispersity, viscosity, surface tension, pH, density). Stable systems were obtained with a fragrance composition concentration within 6⁻15% range. These formulations had a low viscosity and a pH suitable for the skin. Moreover, the obtained results confirmed the protective role of nanoemulsions. The peroxide number measurement (POV) showed that the tested fragrance compositions had a high chemical stability. The results of the microbiological tests confirmed that the obtained products were free of microbiological contamination and were appropriately preserved. The dermatological test results confirmed the safety of the developed preparations.

The Release of Perillyl Alcohol from the Different Kind of Vehicles.

BACKGROUND: Skin cancers are the most common malignancy in humans, and the number of cases has increased dramatically in the past few decades. Therefore, it is very important to carry out studies concerning new and safer anticancer natural agents (e.g. perillyl alcohol) and modern drug delivery systems, such as nanoformulations, which increase their bioavailability. OBJECTIVES: The aim of this work was to obtain different kinds of topical vehicles formulation and compare their efficiency in the release of perillyl alcohol. The release kinetics was determined by using certain selected mathematical models. METHOD: Formulations of a hydrogel, O/W nanoemulsion, O/W macroemulsion and nanostructured lipid carrier were developed as carriers for perillyl alcohol - one of the promising anticancer natural agents. The release study of the active agents was carried out using the Spectra/Por Standard Regenerated Cellulose membrane, at temperature T=320C. The concentration of active agents in the receptor solution was analyzed by high performance liquid chromatography. The release kinetics was determined by using selected mathematical models. RESULTS: The results of our release studies have shown that the highest and comparable amount of perillyl alcohol was released from hydrogel (35.72 ± 0.21%), NLC (35.54 ± 1.48%) and nanoemulsion (34.87 ± 4.49%). The release was found to follow Fickian diffusion in the case of hydrogel and macroemulsion, while an anomalous mechanism was observed in the case of nanoformulations. Nevertheless, the obtained nanoformulations, as well as a conventional hydrogel, may be considered potential vehicles in topical delivery of perillyl alcohol.

NLCs as a potential carrier system for transdermal delivery of forskolin.

Nanostructured lipid carriers (NLC) composed of the substances generally recognized as safe (GRAS) were obtained by using a hot high-pressure homogenization technique (HPH). The influence of the number of homogenization cycles and concentration of a decyl glucoside surfactant on the NLC properties were studied. The system's stability was assessed by macroscopic observation, light backscattering and zeta potential measurements. NLC particle size was measured using dynamic light scattering (DLS). The kinetically stable formulations were loaded with forskolin and selected for in vitro drug permeation study using the Franz cell method. Concentration of forskolin in the receptor solution (i.e. ethanol/PBS mixture) was analyzed with high performance liquid chromatography (HPLC) with UV detection. The obtained results have shown that NLC formulations could be used as effective carriers for forskolin permeation through the skin.

Nano-emulsions as vehicles for topical delivery of forskolin.

Two O/W forskolin-loaded nano-emulsions (0.075% wt.) based on medium chain triglycerides (MCT) and stabilized by a nonionic surfactant (Polysorbate 80 or Polysorbate 40) were studied as forskolin delivery systems. The nano-emulsions were prepared by the PIC method. The mean droplet size of the nano-emulsions with Polysorbate 80 and Polysorbate 40 with oil/surfactant (O/S) ratios of 20/80 and 80% water concentration, measured by Dynamic Light Scattering (DLS), was of 118 nm and 111 nm, respectively. Stability of the formulations, as assessed by light backscattering for 24 h, showed that both nano-emulsions were stable at 25°C. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32°C, using Franz-type diffusion cells. A mixture of PBS/ethanol (60/40 v/v) was used as a receptor solution. The highest flux and permeability coefficient was obtained for the system stabilized with Polysorbate 80 (6.91±0.75 µg · cm-2·h-1 and 9.21 · 10-3±1.00 · 10-3 cm · h-1, respectively) but no significant differences were observed with the flux and permeability coefficient value of forskolin dissolved in oil. The obtained results showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin.

Influence of process parameters on properties of Nanostructured Lipid Carriers (NLC) formulation.

Nanostructured lipid carriers (NLC) are stable colloidal formulations with notable advantages for drug delivery systems. Thanks to their physicochemical stability, biocompatibility, biodegradability and controlled drug release, they have received increasing attention for the last several years. The aim of the study was to prepare and characterize nanostructured lipid carriers (NLC). Both, the effect of the process parameters and the effect of the preemulsion composition on the NLC properties were investigated. In the work, different type of surfactants (i.e. decyl glucoside, Poloxamer188, Tween 80, sodium cholate) and their combinations were used to stabilize NLC dispersions. Moreover, several kinds of solid lipids (modified beeswax, gliceryl behenate, cetyl palmitate and berry wax) and liquid lipids (caprilic/capric triglyceride and decyl oleate) were applied. An ultrasonication method using a probe type sonicator was used to obtain NLC, and the time and energy of the process were modified throuhout. The physicochemical properties of the formulations, such as particle size, size distribution, polidispersity index were studied using the dynamic light scattering (DLS) method. The electrophoretic mobility of obtained particles was also measured, using the Zetasizer Nano ZS Malvern Instrument based on the Laser Doppler Velocimetry (LDV) technique. Knowing the value of electrophoretic mobility of particles for given conditions, the zeta potential was determined. The obtained results showed that the process parameters and the composition of the preemulsion had significant impact on the nanoparticles structure. The optimal formulations size ranged between 60 and 80 nm, and the value of their zeta potential was up to -30mV. The stability of these systems was further confirmed by macroscopic observation.