Preparation and in vivo Distribution of Essential Oil from Alpinia zerumbet Fructus Encapsulated Nanoemulsions / 中国实验方剂学杂志

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B12（VB12） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB12. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Development and characterization of photoprotective nanoemulsions containing Babassu (Orbignya phalerata Mart. ) lipophilic extract

Abstract Oil-in-water photoprotective nanoemulsions (NEs) were developed using Babassu (BBS) lipophilic extract, nonionic surfactants, and low concentrations of organic sunscreens by ultrasonic processing. BBS extract was chosen due to its suitable physicochemical properties (acidity index, peroxide index, refraction index, and relative density) and predominance of saturated fatty acids, identified by gas chromatography-mass spectrometry (GC-MS), which promote biological activities and high oxidative stability. NEs were characterized by mean droplet size, morphology, polydispersity index (PdI), pH, and organoleptic properties, and the physical stability of the NEs was evaluated for 120 days at room temperature. The sun protection factor (SPF) was determined, and the photostability and in vitro cytotoxicity assays were performed for NEs. All NEs remained stable for 120 days, with a droplet size <150 nm and a monomodal distribution profile. The pH values were compatible with the skin's pH. NE3 showed a spherical morphology, with a mean droplet size of 125.15 ± 0.16 nm and PdI of 0.145 ± 0.032. NE3 containing BBS extract and sunscreens presented an SPF of 35.5 ± 3.0, was photostable after 6 h of radiation and was non-cytotoxic to fibroblast cells. Thus, NE3 could be considered a promising formulation for developing synergic plant-extract sunscreen photoprotective products for the market

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Characterization, Antioxidant and Antibacterial Potentials of Tamarindus indica L. Fruit Pulp Extract Loaded O/W Nanoemulsions

Abstract The main purposes of the current study were to formulate o/w nanoemulsions as a carrier for Tamarindus indica (tamarind) fruit pulp extract and to study the antioxidant and antibacterial potentials of nanoemulsions containing tamarind extract, focusing on cosmetic/hygiene applications. The o/w nanoemulsions using a mixture of Tween 80 and Span 80 as an emulsifier (5%w/w) were prepared by a high pressure homogenization process. Two concentrations of sweet tamarind extract, 3.3 and 6.6%w/w, based on the bioactivity study, were incorporated into the blank nanoemulsions to produce loaded nanoemulsions, F1-3.3TE (3.3%) and F1- 6.6TE (6.6%). As compared with the unloaded nanoemulsion, both tamarind extract loaded nanoemulsions showed reduced pH and significantly increased viscosity. Overall, the loaded nanoemulsions had droplet sizes of approximately 130 nm, zeta potential around -38 mV and polydispersity index (PDI) values less than 0.2. The nanoemulsion F1-3.3TE had better stability (e.g. significantly greater % tartaric acid content and lesser PDI value) than the nanoemulsion F1-6.6TE did. The antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay revealed that the nanoemulsions F1-3.3TE and F1-6.6TE had scavenging activities of 81.66 ± 0.77% and 63.80 ± 0.79%, respectively. However, antioxidant activity of these two formulations decreased under stress conditions (heating-cooling cycles). Such incidence did not occur for their antibacterial properties investigated by agar well diffusion technique. The two formulations exhibited inhibition zones of approximately 24.0-27.7 mm against Staphylococcus aureus and Staphylococcus epidermidis, responsible for malodor of underarms. The results suggest the potential of using sweet tamarind pulp extract loaded nanoemulsions as hygiene products.

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: A current overview of

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of

Preparation of resveratrol nanoemulsions and evaluation their pharmacokinetics profiles in rats in vivo / 中草药

Objective :To fabricate resveratrol nanoemulsions and probe their pharmacokinetics profiles in rats in vivo. Methods The nanoemulsions of resveratrol were tailored by using aethylis oleas as the oil phase, Cremophor RH40 as emulsifiers, absolute alcohol as co-emulsifiers, respectively. The formulation was optimized by pseudo-ternary phase diagrams and their physicochemical properties of nanoemulsions were characterized by particle size distribution, transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). The pharmacokinetics experiments were also performed in rats after gavage and the plasm concentration of resveratrol were determined by HPLC as well as the profiles of pharmacokinetic parameters were obtained by Drug and Statistics (DAS) software. Results: The formula of nanoemulsions were as follows: the ratio of resveratrol-aethylis oleas-mixture surfactant- distilled water was 1:10:24:65. The average particle size diameters of prepared resveratrol nanoemulsions were about 40 nm and the droplets of nanoemulsions were in spherical shape observed by TEM. The results of IR disclosed that the active trans-resveratrol presented in the oil droplet of the nanoemulsions. Compared with resveratrol suspensions, the bioavailability of resveratrol nanoemulsions was increased 1.45-fold, and Cmax reached to 1.93-fold. Conclusion : These results indicated that nanoemulsions may be a promising tool for the delivery of resveratrol.

Transdermal characteristics and mechanism of asiaticoside nanoemulsions and asiaticoside nanoemulsions-based gels / 中国中药杂志

To prepare the asiaticoside nanoemulsions (ASI-NEs) and asiaticoside nanoemulsions-based gels (ASI-NBGs), compare them with the commercial cream of asiaticoside (ASI-C) in terms of transdermal characteristics, and investigate the transdermal mechanism of ASI-NEs and ASI-NBGs. Their transdermal characteristics were studied by using Franz diffusion cells. The effect of topical ASI-NEs and ASI-NBGs on ultrastructure of rabbit skin was evaluated by using HE staining method. The localization and the permeation pathway of asiaticoside were visually investigated by using laser scanning confocal microscope (CLSM). The transdermal studies in vitro showed that the cumulative amount of ASI permeated from ASI-NEs and ASI-NBGs at 12 h after application were (3 504.30±180.93), (1 187.40±128.88) μg·cm⁻² respectively, 6.57, 2.23 times of that in the control group of ASI-C; the drug deposition of ASI-NEs and ASI-NBGs in skin was (159.48±7.47), (120.53±5.71) μg·cm⁻² respectively, 5.93, 4.48 times of that of ASI-C. HE staining of the rabbit skin after application of ASI-NEs and ASI-NBGs showed that the epidermis structure was basically intact; stratum corneum was loosed and the keratin fragment was increased; at the same time, the gap of prickle cell was increased and the basal cells were arranged loosely. The study of CLSM showed that significant percutaneous enhancer effect was observed for ASI-NEs after the topical application of 6 h, as the fluorescent compound was penetrated in the dermis and diffused uniformly. The fluorescence area and the integral optical density (IOD) were 28.81, 32.51 times of that in the FITC aqueous solution group, respectively. The fluorescent preparations showed strong fluorescence in the epidermis, but weak in deeper layers; with the increase of treatment time, the fluorescence in deeper layer was increased and stronger in skin appendages. The prepared ASI-NEs and ASI-NBGs have good transdermal characteristics and the transdermal mechanism is related to breaking the ultrastructure of stratum corneum and penetrating by the path of skin adnexa.

Study on transdermal mechanism of Sophora flavescens alkaloids nanoemulsions and nanoemulsion-based gels / 中草药

Objective: To prepare nanoemulsions (NE) and nanoemulsion-based gels (NBGs) with Sophora flavescens alkaloids (SFA) as model drug to illuminate its mechanism of transdermal delivery basically. Methods: Using scanning electron microscopy (SEM) method, HE staining method, and confocal laser scanning microscope (CLSM) method to investigate the effect of SFA-NEs and SFA-NBGs on stratum corneum (SC) and ultrastructure. Results: The results of SEM showed that the SC of normal mouse was smooth and finishing. And slightly crimp the saline group after 6 h of treatment appeared, while it was damaged in varying degrees hurt after 2 h and 6 h of action by SFA-NEs and SFA-NBGs, respectively. HE staining results indicated that the skin structure of saline group was basically intact. But the hierarchy structure of SFA-NBGs group was not obvious, basal layer arranged unclearly and SC loosed apparently, as well as that the hierarchy structure of SFA-NEs group disordered, the gap increased, SC loosed and thinned. The result of confocal laser scanning microscope indicated that fluorescence in surface was stronger while weaker in depth among control group, SFA-NEs group, and SFA-NBGs group, and fluorescence in hair follicles and around its appendages was also stronger. Conclusion: SFA-NEs and SFA-NBGs could permeate skin mainly through breaking SC and ultrastructure so as to perform therapeutic action. At the same time, hair follicles and its appendages play a role on drug transdermal course.

Study on paclitaxel-oleic acid and Brucea javanica oil core-matched nanoemulsions drug delivery / 中草药

Objective: To optimize the preparation method of paclitaxel-oleic acid (PTX-OA)/Brucea javanica oil (BJO) core- matched nanoemulsions (CMNEs). Methods: PTX-OA/BJO was synthesized by esterification of PTX and OA, and determined by HPLC. Ultrasionic emulsification was used to prepare the PTX-OA/BJO CMNEs. The concentration of oil phase (A), quality of polysorbate 80 (B), and ultrasonic power (C) were selected as the significant factors after single-factor experiments and applied in L16(43) orthogonal array design with the average particle size as criterion. In addition, the physicochemical properties and cytotoxicity of PTX-OA/BJO CMNEs were tested. Results: Linear range of PTX-OA was 5-25 μg/mL, Y = 12.709 X + 6.252 0, r = 0.999 5. The optimized conditions of PTX-OA/BJO CMNEs were as follows: The concentration of oil phase was 6.50 mg/mL, the mass ratio of polysorbate 80 to oil phase was 3.5: 6.5 and the ultrasonic power was 120 W. The CMNEs prepared by the optimal conditions showed an entrapment efficiency of (100.6 ± 1.9)% and the nanoscale particle size was (108.7 ± 2.3) nm, PDI was 0.232 ± 0.038. The morphology of CMNEs examined by TEM exhibited a uniform and spherical shape. In vitro drug release was up to 67% after 48 h. After PTX-OA/BJO CMNEs sealed in a bottle were stored at 4 ℃ for 60 h, the average particle size and entrapment efficiency had no significant change. The cytotoxicity in vitro showed that the combined PTX-OA/BJO CMNEs could obviously inhibit the proliferation of HepG-2 cells. Conclusion: The current study demonstrates the feasibility of incorporating PTX-OA and BJO into a single CMNEs for the synergism in cancer therapy. Furthermore, the preparation of PTX-OA/BJO CMNEs has the advantages of practicability and simple operation, as well lays the foundation for the further mechanism research of the combined paclitaxel and BJO in oncotherapy.

Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.

Improved Antitumor Efficacy of Hyaluronic Acid-Complexed Paclitaxel Nanoemulsions in Treating Non-Small Cell Lung Cancer

Paclitaxel (PTX) is a effectively chemotherapeutic agent which is extensively able to treat the non-small cell lung, pancreatic, breast and other cancers. But it is a practically insoluble drug with water solubility less than 1 μg/mL, which restricts its therapeutic application. To overcome the problem, hyaluronic acid-complexed paclitaxel nanoemulsions (HPNs) were prepared by ionic complexation of paclitaxel (PTX) nanoemulsions and hyaluronic acid (HA) to specifically target non-small cell lung cancer. HPNs were composed of dl-α-tocopheryl acetate, soybean oil, polysorbate 80, ferric chloride, and HA and fabricated by high-pressure homogenization. The HPNs were 85.2 ± 7.55 nm in diameter and had a zeta potential of −35.7 ± 0.25 mV. The encapsulation efficiency was almost 100%, and the PTX content was 3.0 mg/mL. We assessed the in vivo antitumor efficacy of the HPNs by measuring changes in tumor volume and body weight in nude mice transplanted with CD44-overexpressing NCI-H460 xenografts and treated with a bolus dose of saline, Taxol®, PTX nanoemulsions (PNs), or HPNs at a dose of 25 mg/kg. Suppression of cancer cell growth was higher in the PN- and HPN-treated groups than in the Taxol® group. In particular, HPN treatment dramatically inhibited tumor growth, likely because of the specific tumor-targeting affinity of HA for CD44-overexpressed cancer cells. The loss of body weight and organ weight did not vary significantly between the groups. It is suggest that HPNs should be used to effective nanocarrier system for targeting delivery of non-small cell lung cancer overexpressing CD44 and high solubilization of poorly soluble drug.

Bio-Nanotechnology for Active Food Packaging.

The most commonly used packaging material is associated with environmental issues as they are non-degradable in nature. The number of attempts are made for developing the eco-friendly degradable biopolymers as ideal food packaging. The biopolymers developed are not commercialized as they have poor mechanical strength and resistance properties. Thus to enhance the following faults in the reinforcing material are added which resulted in the composites formation. During various food processing operations the nanotechnology approach is employed such as encapsulation of the material in the nanoparticles, which can be delivered to the targeted site, enhancement of the flavor, integration of antibacterial agents with the nanoparticle in the food, enhancement of shelf-life for storage, and contamination sensing. Food packaging substances synthesized by nanotechnology may increase the shelf-life of the food as they provide resistive packaging, increase the level of food safety, liberate the preservatives for enhancing the life of the food and notify the consumer either the food is consumable or spoiled. Nano-supplements are integrated by the encapsulation method for efficient dietary as well as drug delivery systems. Nano-materials are not well evaluated for the health risk and environmental issues associated with it even the side-effects are unexploited. Various authorities are working prompt designing of guidelines and legislation policies for further acceptance of Nano-based materials in food packaging systems. Biologically synthesized nanoparticles will serve as a significant tool to conquer present contests that are linked with food packaging constituents.

The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications

ABSTRACT Vegetable oils present important pharmacological properties, which gained ground in the pharmaceutical field. Its encapsulation in nanoemulsions is considered a promising strategy to facilitate the applicability of these natural compounds and to potentiate the actions. These formulations offer several advantages for topical and systemic delivery of cosmetic and pharmaceutical agents including controlled droplet size, protection of the vegetable oil to photo, thermal and volatilization instability and ability to dissolve and stabilize lipophilic drugs. For these reasons, the aim of this review is to report on some characteristics, preparation methods, applications and especially analyze recent research available in the literature concerning the use of vegetable oils with therapeutic characteristics as lipid core in nanoemulsions, specially from Brazilian flora, such as babassu (Orbignya oleifera), aroeira (Schinus molle L.), andiroba (Carapa guaianiensis), casca-de-anta (Drimys brasiliensis Miers), sucupira (Pterodon emarginatus Vogel) and carqueja doce (Stenachaenium megapotamicum) oils.

On the use of nanotechnology-based strategies for association of complex matrices from plant extracts

AbstractDepending on the method of extraction, plant extracts can contain an enormous variety of active molecules, such as phenolic compounds, essential oils, alkaloids, among others. In many cases, from a pharmacological point of view, it is interesting to work with crude extract or fractions instead of a single isolated compound. This could be due to multi-targeting effect of the extract, lack of knowledge of the active compounds, synergistic effect of the extract compounds, among others. In any case, in order to achieve a final product some issues must be overcome, including poor stability, solvent toxicity, and low solubility of the bioactive compound. Recently many nanotechnology-based strategies have been proposed as an alternative to solve these problems, especially liposomes, nanoemulsions and nanoparticles. In this sense, the present work aims to review the main nanotechnological approaches used for association of different plant extracts and the main achievements from using these technologies.

Absorption and distribution characteristics of terbinafine hydrochloride nanoemulsions in cornea after instillation / 中华实验眼科杂志

Background Nanoemulsions (NEs) is one of the most popular ophthalmic colloidal drug delivery system due to its long-term stability, low toxicity and irritancy, considerable capacity for solubilization of lipophilic drug molecules and great potential in bioavailability improvement.The cornea pathway is the main route of intraocular absorption after topical use of NEs.Though NEs possess numerous physiological and physicochemical advantages,the use of NEs cannot always obtain satisfactory results.Objective This study was to investigate the impacts of epithelium and stroma on the corneal permeation of topical ophthalmic terbinafine hydrochloride nanoemulsions (TH-NEs).Methods TH-NEs was prepared by the self-emulsification method.The size and Zeta potential of the oil droplets in the formulation were analyzed using a dynamic light-scattering particle size analyzer.The high performance liquid chromatography (HPLC) was used for the in vitro release study.Sixty New Zealand albino rabbits were randomly divided into intact cornea group and cornea epithelium debrided group.The cornea epithelium of the left eyes was debrided in the cornea epithelium debrided group.The TH-NEs were instilled into the lower conjunctival sac of left eyes.Six rabbits were executed from each group 15,30,60,120 and 240 minutes after dosing,respectively.The corneas were collected and analyzed by HPLC.The fluorescein diacetate (FDA) was used to label the TH-NEs.Two C57BL/6 mice with left cornea epithelium debrided and 2 normal mice were used for the fluorescence tracing study.The fluorescence distribution of FDA labeled TH-NEs was observed by a two-photon laser confocal scanning microscope 30 minutes and 60 minutes after single instillation.Results The average size and Zeta potential of the oil droplets were 51.37 nm and-0.232 7 mV respectively,and 0.482％ of encapsulated drugs was released from the TH-NEs after 12 hours.The peak concentrations of TH in the intact cornea and epithelium debrided cornea were (17.85 ± 2.79) μg/g and (4.40± 1.75) μg/g respectively, which occurred 15 minutes postdose.The drug concentrations in the intact cornea were significantly higher than that in the debrided cornea 15,30,60 and 120 minutes after dosing, with significant differences between them (t =9.998,8.658,6.903,7.576;all at P=0.000).The fluorescence was observed in the cornea epithelium when the cornea was intact.The fluorescence intensity in the superior layer of corneal epithelium was obviously higher than that in the deep layers of corneal epithelium 30 minutes and 60 minutes after dosing.No fluorescence was observed in the cornea stroma of both eyes.Conclusions The cornea epithelium is the main of absorption and distribution position of TH-NEs.The cornea stroma is the dominating permeation barrier for the intraocular transportation of the TH-NEs.The cornea stroma may stop the permeation of TH-NEs by molecular exclusion mechanism.

Citotoxic activity evaluation of essential oils and nanoemulsions of Drimys angustifolia and D. brasiliensis on human glioblastoma (U-138 MG) and human bladder carcinoma (T24) cell lines in vitro

The species Drimys angustifolia Miers and D. brasiliensis Miers, commonly known as "casca-de-anta", have in their leaves essential oils that can confer cytotoxic effects. In this study, we evaluated the citotoxic effects of the volatile oils from these two species. We also proposed a nanoemulsion formulation for each of the species and assessed the in vitro cytotoxicity on U-138 MG (human glioblastoma) and T24 (human bladder carcinoma) cell lines. The plant chemical composition was evaluated by gas chromatography coupled to mass spectrometer. Furthermore, the nanoemulsions were prepared and characterized. Our results showed that; bicyclogermacrene (19.6%) and cyclocolorenone (18.2%) were the most abundant for the D angustifolia oil and D brasiliensis oil, respectively. Both nanoemulsions, D angustifolia and D brasiliensis appeared macroscopically homogeneous and opalescent bluish liquids, with nanometric mean diameters of 168 nm for D brasiliensis and 181 nm for D angustifolia. The polydispersity indices were below 0.10, with an acid pH of 4.7-6.3, and negative zeta potentials about -34 mV. The results of transmission electron microscopy showed that droplets are present in the nanometer range. Only the D brasiliensis oil was efficient in reducing the cell viability of both U-138 MG (42.5%±7.0 and 67.8%±7.8) and T24 (33.2%±2.8, 60.3%±1.6 and 80.5%±8.8) cell lines, as assessed by MTT assay. Noteworthy, similar results were obtained with cell counting. Finally, D brasiliensis oil incubation caused an increase of annexin-V and propidium iodite population, according to evaluation by cytometry analysis, what is characteristic of late apoptosis. The results presented herein lead us to consider the potential therapeutic effects of the essential oils and nanoformulations as novel strategies to inhibit tumor growth.

Nanoemulsions as vehicles for transdermal delivery of glycyrrhizin

The present investigation aims to evaluate an isotropic and thermodynamically stable nanoemulsion formulation for transdermal delivery of glycyrrhizin (GZ), with minimum surfactant and cosurfactant (Smix) concentrations that could improve its solubility, permeation enhancement, and stability. Pseudo-ternary phase diagrams were developed and various nanoemulsion formulations were prepared using soyabean oil as oil, Span 80, Brij 35 as a surfactant and isopropyl alcohol as a cosurfactant. Nanoemulsion formulations that passed the thermodynamic stability tests were characterized for pH, viscosity and droplet size using a transmission electron microscopy. The transdermal ability of glycyrrhizin through human cadaver skin was determined using Franz diffusion cells. The in vitro skin permeation profile of the optimized nanoemulsion formulation (NE2) was compared to that of conventional gel. A significant increase in permeability parameters such as steady-state flux (Jss) and permeability coefficient (Kp) was observed in the optimized nanoemulsion formulation (NE2), which consisted of 1 percent wt/wt of mono ammonium glycyrrhizinate (MAG), 32.4 percent Span 80, 3.7 percent Brij 35, 10 percent isopropyl alcohol, 46.5 percent soyabean oil and 6.4 percent distilled water. No obvious skin irritation was observed for the studied nanoemulsion formulation (NE2) or the gel. The results indicated that nanoemulsions are promising vehicles for transdermal delivery of glycyrrhizin through human cadaver skin, without the use of additional permeation enhancers, because excipients of nanoemulsions act as permeation enhancers themselves.

O objetivo da investigação é avaliar uma nanoemulsão isotrópica termodinamicamente estável para a administração transdérmica da glicirrizina (GZ), com concentrações mínimas de tensoativo e co-tensoativo (Smix), que poderiam melhorar a sua solubilidade, a permeação e a estabilidade. Os diagramas pseudo-ternários de fase foram desenvolvidos e diversas nanoemulsões foram preparadas com óleo de soja como óleo, Span 80, Brij 35 como tensoativos e álcool isopropílico como co-tensoativo. As nanoemulsões que passaram por testes de estabilidade termodinâmica foram caracterizadas por pH, viscosidade, tamanho de gota e microscopia eletrônica de transmissão. A capacidade transdérmica da glicirrizina em passar através da pele de cadáver humano foi determinada por células de difusão de Franz. O perfil in vitro de permeação cutânea da formulação otimizada (NE2) foi comparada com a de gel convencional. Observou-se aumento significativo nos parâmetros de permeabilidade, como fluxo de equilíbrio (JSS) e coeficiente de permeabilidade (Kp) na formulação otimizado (NE2), que consistiu de 1 por cento wt/wt de monoglicirrizinato de amônio (MAG), 32,4 por cento de Span 80, 3,7 por cento de Brij 35, 10 por cento de álcool isopropílico, 46,5 por cento de óleo de soja e 6,4 por cento de água destilada. Não se observou irritação óbvia da pele para as nanoemulsões estudadas (NE2) ou de gel. Os resultados indicaram que nanoemulsões são promissores veículos para a administração transdérmica de glicirrizina através da pele de cadáveres humanos, sem o uso adicional de promotor de permeação, porque excipientes de nanoemulsões atuam como promotores de permeação.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1 percent cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580 percent/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319 percent/g) was greater than CE uptake (0.0595 ± 0.0207 percent/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.