Essential oils are natural products with a complex composition. Terpenes are the most common class of chemical compounds present in essential oils. Terpenes and the essential oils containing them are ...widely used and investigated by their pharmacological properties and permeation-enhancing ability. However, many terpenes and essential oils are sensitive to environmental conditions, undergoing volatilization and chemical degradation. In order to overcome the chemical instability of some isolated terpenes and essential oils, the encapsulation of these compounds in nanostructured systems (polymeric, lipidic, or molecular complexes) has been employed. In addition, nanoencapsulation can be of interest for pharmaceutical applications due to its capacity to improve the bioavailability and allow the controlled release of drugs. Topical drug administration is a convenient and non-invasive administration route for both local and systemic drug delivery. The present review focuses on describing the current status of research concerning nanostructured delivery systems containing isolated terpenes and/or essential oils designed for topical administration and on discussing the use of terpenes and essential oils either for their biological activities or as permeation enhancers in pharmaceutic formulations.
Carbamazepine (CBZ), a widely used anticonvulsant drug, is a poorly soluble drug with no parenteral treatment available for patients. This study was aimed at developing a nanoemulsion for CBZ ...intravenous delivery. The spontaneous emulsification method was used to prepare different formulations containing 2
mg/mL CBZ. Likewise, a 2
2 full factorial experimental design was applied to study the influence of two independent variables (type of oil and type of lipophilic emulsifier) on emulsion physicochemical characteristics. The nanoemulsions were evaluated concerning droplet size, zeta potential, viscosity, drug content and association to oily phase. The formulation, which presented the best characteristics required for intravenous administration was selected and refined with respect to the lipophilic emulsifier content (increase from 5% to 6% of soy lecithin). This formulation was characterized and kept its properties in a satisfactory range over the evaluated period (3 months), i.e. droplet size around 150
nm, drug content around 95% and zeta potential around −40
mV. The transmission electron microscopy revealed emulsion droplets almost spherical in shape with an amorphous core, whereas the
in vitro release profile assessed by dialysis bags demonstrated a release kinetics square root time dependent, with 95% of ca. having been released within 11
h.
Copaiba oil is used as a popular medicine in the Amazonian forest region, especially due to its anti-inflammatory properties. In this paper, we describe the formulation of hydrogel containing copaiba ...oil nanoemulsions (with positive and negative charges), its skin permeation, and its anti-inflammatory activity in two
in vivo
models: mouse ear edema and rat paw edema. Three hydrogels were tested (Carbopol
®
, hydroxyethylcellulose and chitosan), but only Carbopol
®
and hydroxyethylcellulose hydrogels presented good stability and did not interfere with the nanoemulsions droplet size and polydispersity index. In skin permeation assay, both formulations, positively charged nanoemulsion (PCN) and negatively charged nanoemulsion (NCN), presented a high retention in epidermis (9.76 ± 2.65 μg/g and 7.91 ± 2.46 μg/cm
2
, respectively) followed by a smaller retention in the dermis (2.43 ± 0.91 and 1.95 ± 0.56 μg/cm
2
, respectively). They also presented permeation to the receptor fluid (0.67 ± 0.22 and 1.80 ± 0.85 μg/cm
2
, respectively). In addition, anti-inflammatory effect was observed to NCN and PCN with edema inhibitions of 69 and 67% in mouse ear edema and 32 and 72% in rat paw edema, respectively. Histological cuts showed the decrease of inflammatory factors, such as dermis and epidermis hyperplasia and inflammatory cells infiltration, confirming the anti-inflammatory effect from both copaiba oil nanoemulsions incorporated in hydrogel.
•A GC method to quantify 1-nitro-2-phenylethane and methyleugenol was proposed.•The focus is to determine the skin retention after Aniba canelilla oil application.•Solid-phase microextraction ...conditions were optimized by 33 Box-Behnken design.•The calibration curves required a data linearization using Log10.•Permeation assay revealed pronounced retention in receptor fluid and dermis.
Aniba canelilla (H.B.K.) Mez is an aromatic plant from the Amazon region whose essential oil has 1-nitro-2-phenylethane (NP) and methyleugenol (ME) as major compounds. Despite of the scientifically proven antifungal and anti-inflammatory activities for these compounds, there is no report up to date about the topical permeation or quantification of NP and ME on skin samples. The aim of this study was the validation of an optimized bioanalytical method by solid-phase microextraction in headspace mode in gas chromatograph with flame ionization detector (HS-SPME-GC-FID) for the determination of NP and ME from the oil in different samples from permeation study, such as porcine ear skin (PES) layers (stratum corneum, epidermis and dermis) and receptor fluid (RF). For this propose polydimethylsiloxane fibers (100 μm) were used and HS-SPME extraction condition consisted of 53 °C, 21 min, and 5% w.v−1 NaCl addition. The wide range of the calibration curve (2.08–207.87 μg mL−1 for NP and 0.40–40.41 μg mL−1 for ME), the presence of matrix interferences and the intrinsic characteristics of HS-SPME required a data linearization using Log10. Thereby, data and the gained results presented homoscedasticity, normalization of residues and adequate linearity (r2 > 0.99) and accuracy for both compounds. In order to verify the applicability of the validated method, the HS-SPME-GC-FID procedure was performed to determine the amount of NP and ME permeated and retained in samples after Franz diffusion cell study from different dosages (20, 100 and 200 μL) of A. canelilla oil. Compounds permeation showed a progressive increase and penetration dependence based on the dosage applied. Furthermore, retention was in order receptor fluid >> dermis >> epidermis >> stratum corneum for both compounds, suggesting NP and ME could penetrate deep tissue, probably due to the partition coefficient, mass, size, and solubility of these compounds. In conclusion, the proposed method by HS-SPME-GC-FID to quantify 1-nitro-2-phenylethane and methyleugenol from Aniba canelilla essential oil was able to determine selectively, precisely and accurately these main compounds in skin permeation samples.
•A HS-GC/MS method was validated for β-caryophyllene analysis in skin samples.•This new method was sensitive, practical and solvent-free.•The permeation of β-caryophyllene from crude copaiba oil and ...nanoemulsion was compared.•β-caryophyllene achieved the dermis from the nanoemulsion.
Copaiba oil is largely used in the Amazonian region for the treatment of inflammation, and recent studies demonstrated that one of the major components of the oil, β-caryophyllene (CAR), is a potent anti-inflammatory. The nanoemulsification of this oleoresin, which has unctuous character, converts it in a more acceptable hydrophilic formulation and may improve CAR penetration through the skin due to the small droplet size and the high contact surface afforded by the nanoemulsions. This paper describes the validation of a novel, sensitive, practical and solvent free method that uses gas chromatography in headspace mode coupled with mass spectrometry to evaluate the skin permeation/retention of CAR from the crude copaiba oil and its nanoemulsion. Our results show that the bioanalytic method was fully validated, demonstrating linearity (r2>0.99), specificity (no peaks co-eluting with CAR retention time), precision (RSD<15%) and accuracy (recovery>90%) within the accepted parameters and that the copaiba oil nanoemulsion presented a better skin penetration compared to the crude oil, with CAR achieving the most profound layer of the skin, the dermis.
The essential oil of Aniba canelilla (Kunth) Mez (EOAC), an Amazon plant composed of a rare nitro compound, has shown scientific evidence of antifungal activity but is still unexplored against ...dermatophytes. The antifungal susceptibility of EOAC and its main compound, 1-nitro-2-phenylethane (NP), was evaluated against dermatophytes (Trichophyton rubrum, T. mentagrophytes and Microsporum canis), evidencing antifungal activity with an inhibitory concentration lower than 256 μg/mL. The mechanism of action was also evaluated, and it is suggested that EOAC and NP have fungicidal action in the fungal membrane, since the antifungal activity occurs through a modification of the shape of the conidial structures of the fungus, showing the permeability of the intracellular content due to the visually observed plasmolysis and cytosolic extravasation through an osmotic process. These results suggest the essential oil and its main compound are promising plant-derived alternatives for treating ungual dermatophytosis.
Currently, there is an increasing interest on the development of topical formulations containing rosmarinic acid (RA) due to its well-documented antioxidant activity. This study aimed to develop and ...validate a stability-indicating ultra-fast liquid chromatography (UFLC) method for the determination of RA in nanoemulsions, porcine skin and nasal mucosa intended to be applied in permeation/retention studies and for development of topical nanoemulsions. Chromatographic separation was carried out using a C18 column packed with 2.6 μm particle size in isocratic conditions using as mobile phase water:acetonitrile (83:17, v/v), acidified with 0.1% trifluoracetic acid (v/v), with a total time of analysis of 3.5 min and detection at 330 nm. RA analysis was specific in the presence of both non-biological (blank nanoemulsion and receptor fluid) and biological matrices (porcine ear skin and porcine nasal mucosa). No interference of degradation products of RA was verified after different stress conditions such as acidic, alkaline, oxidative, light exposure (UV-A and UV-C) and thermal demonstrating the method stability-indicating property. The analytical (0.1–10.0 μg·mL−1) and bioanalytical (0.5–10.0 μg·mL−1) linearity was proved by analysis of the calibration curves of RA and no matrix effect was observed. The method was sensitive, precise and accurate, and showed recovery higher than 85%. The method was considered robust as evaluated by a Plackett-Burman experimental design. In the validated conditions, the RA was determined in the nanoemulsions obtained by spontaneous emulsification procedure (1.007 ± 0.040 mg·mL−1), porcine ear skin (1.13 ± 0.19 μg·cm−2) and nasal mucosa (22.46 ± 3.99 μg·cm−2) after retention/permeation studies. Thus, a highly sensitive, simple, fast and stability-indicating method was developed for RA analysis during the development of topical nanoemulsions and bioanalytical assays in complex matrices.
•A simple and fast analytical and bioanalytical UFLC method for RA was validated.•The method proved to be stability-indicating using different stress conditions.•The method was selective, linear, precise, accurate and robust with low matrix effect.•The method was able to estimate RA incorporated in pharmaceutical nanoemulsions.•The method was applied to assay RA in skin and nasal mucosa samples.
Essential oils are natural products extracted from plants that present volatile and thermolabile characteristics. Essential oils have become products of interest in many fields, including the ...pharmaceutical, due to their medicinal properties. In recent years, the interest in the encapsulation of essential oils in nanometric systems for therapeutic approaches has risen and a number of studies have been published. This review intended to set a panorama on the research within this field through a data survey and identify the organic nanostructured systems, the preparation techniques and analytical quantification methods employed. Many techniques used to prepare nanosystems loaded with essential oils involve heating or solvent evaporation steps that may damage their composition. In this context, the quantification of essential oil on the final nanosystems is impaired. However, in more than half of the research papers, the quantification is ignored or an indirect quantification is performed, assuming no volatilisation upon formulation processes. Analytical methods used to assess essential oil encapsulation efficiency were discussed regarding their suitability.
Display omitted
•A data survey was done to set a panorama of the research concerning the nanoencapsulation of EO for medicinal purposes.•Encapsulation of EO in nanosystems has been studied in the last decade and raised in 2015 and the following years.•Nanoencapsulation of EO many times involve heating and solvent evaporation steps, causing volatilization and/degradation.•Many studies evaluated do not perform the quantification of chemical markers on the EO after the nanoencapsulation.•Among the studies that quantify EO, a few techniques are employed, but not always suitable for the purpose.
Sesquiterpene compounds are applied as permeation promoters in topical formulations. However, studies exploring their impact on nanostructured systems, changes in permeation profile, and ...consequently, its biological activity are restricted. This study aimed to investigate the correlation between the skin permeation of the major sesquiterpenes, beta-caryophyllene, and caryophyllene oxide from the oleoresin of Copaifera multijuga, after delivery into topical nanoemulgels, and the in vivo antiedematogenic activity. First, ten nanoemulgels were prepared and characterized, and their in vitro permeation profile and in vivo anti-inflammatory activity were evaluated. In equivalent concentrations, β-caryophyllene permeation was greater from oleoresin nanoemulgels, resulting in greater in vivo antiedematogenic activity. However, an inverse relationship was observed for caryophyllene oxide, which showed its favored permeation and better in vivo anti-inflammatory effect carried as an isolated compound in the nanoemulgels. These results suggest that the presence of similar compounds may interfere with the permeation profile when comparing the profiles of the compounds alone or when presented in oleoresin. Furthermore, the correlation results between the permeation profile and in vivo antiedematogenic activity corroborate the establishment of beta-caryophyllene as an essential compound for this pharmacological activity of C. multijuga oleoresin.
There is a growing interest in the pharmaceutical field concerning isoflavones topical delivery systems, especially with regard to their skin care properties and antiherpetic activity. In this ...context, the present work describes an ultra-fast liquid chromatography method (UFLC) for determining daidzein, glycitein, and genistein in different matrices during the development of topical systems containing isoflavone aglycones (IA) obtained from soybeans. The method showed to be specific, precise, accurate, and linear (0.1 to 5µgmL−1) for IA determination in soybean acid extract, IA-rich fraction obtained after the purification process, IA loaded-nanoemulsions, and topical hydrogel, as well as for permeation/retention assays in porcine skin and porcine esophageal mucosa. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability indicating UFLC method was verified by submitting IA to acidic, alkaline, oxidative, and thermal stress conditions, and no interference of degradation products was detected during analysis. Mass spectrometry was performed to show the main compounds produced after acid hydrolysis of soybeans, as well as suggest the main degradation products formed after stress conditions. Besides the IA, hydroxymethylfurfural and ethoxymethylfurfural were produced and identified after acid hydrolysis of the soybean extract and well separated by the UFLC method. The method’s robustness was confirmed using the Plackett-Burman experimental design. Therefore, the new method affords fast IA analysis during routine processes, extract purification, products development, and bioanalytical assays.
Display omitted
•An analytical and bioanalytical UFLC method for isoflavone aglycones was validated.•Acid hydrolysis of soybeans was performed to obtain the isoflavone aglycones.•Extract impurities as hydroxymethylfurfural and ethoxymethylfurfural were detected.•A pure rich-fraction was produced and incorporated in nanoemulsions and hydrogels.•Permeation assays in porcine skin or porcine esophageal mucosa were performed.
PDF
