Optimized Nanoemulsion Formulation Research Articles

Formulation Development, Characterization, and Therapeutic Evaluation of Ethanolic Extract of L. speciosa Leaves in Breast Cancer

Background: Due to its possible antioxidant, anti-tumor, anti-diabetic, and anti-inflammatory qualities, Lagerstroemia speciosa (Banaba) (LS) is receiving more attention in med-ical therapy. LS is a natural chemical with few adverse effects and low toxicity, although it has poor water solubility and absorption. Aims and Objectives: This study aimed to create a nanoemulsion formulation utilising an ethanol-ic extract of LS leaves and test it for anticancer activities in the MCF-7 cell line. Methods: Lemongrass oil, Cremophor EL as the surfactant, and Transcutol HP as the co-surfactant were used to create the nanoemulsion. It was done to characterize the ethanolic extract of LS leaves optimised nanoemulsion (ELSN). The MTT test against the MCF-7 cell line was used to assess the anticancer efficacy of ELSN. Results: The average particle size of the optimized nanoemulsion formulation was 91.22 nm with a PDI value of 0.224, indicating a monodispersed system. Transmission electron microscopy has validated the spherical shape of droplet size. Nanoemulsion components, in association with herbal extract, contributed to a zeta potential value of -4.73 Mv. It was discovered that ELSN IC50 was 75.13 ± 3.29 μg/mL. Conclusion: This study confirms that the development of ELSN improves the poor water solu-bility and bioavailability of the drug as well as enhances the therapeutic efficacy.

Antioxidant Activity, Formulation, Optimization and Characterization of an Oil-in-Water Nanoemulsion Loaded with Lingonberry (Vaccinium vitis-idaea L.) Leaves Polyphenol Extract.

The active ingredients in lingonberry leaves and their beneficial properties to the human body have been well confirmed. In order to improve the stability and antioxidant activity of the active ingredients in lingonberry leaves, the response surface optimization method was used to prepare an oil-in-water nanoemulsion of polyphenol extract from lingonberry leaves. The active components in the extract were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UPLC-TQ-MS), and bioactive compounds such as apigenin, sorbitol, and hesperidin were mainly found. Nanoemulsion droplets of 120 nm in diameter were prepared using ultrasonic emulsification. The optimal nanoemulsion formulation was determined through rigorous testing, and it was determined to be 10% (w/w) lingonberry extract and 20% (w/w) medium chain triglyceride (MCT). Additionally, a surfactant mixture was used, which combined soy protein isolate (SPI) and whey protein isolate (WPI) at 4% (w/w). The preparation method utilized ultrasonic emulsification, applying an ultrasonic power of 360 W for a duration of 300 s. The antioxidant activity (DPPH inhibition rate, ABTS inhibition rate and total reducing power) of the lingonberry nanoemulsion was significantly higher than that of the lingonberry polyphenol (LBP) extract. The nanoemulsion prepared using the optimal formulation had an entrapping efficiency of 73.25% ± 0.73% and a diameter of 114.52 ± 0.015 nm, with a satisfactory particle size of nanoscale and a PDI of 0.119 ± 0.065, demonstrating good stability of the emulsion.

Nanoemulsion-Based Strategy for Maximizing Nitrofurantoin Absorption: In-vitro and In-vivo Investigations.

The main objective of the current research work is to improve the absorption of Nitrofurantoin (NFT) by minimizing gastrointestinal (GI) intolerance and variations in its absorption by formulating the drug into a nanoemulsion (NE). Based on the highest saturation solubility of NFT, soybean oil, transcutol HP, and labrafil M1944CS were selected as oil, co-surfactant, and surfactant, and a Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size, highest zeta potential, and higher drug release and hence was selected for further evaluation. Optimized formulation (NF5) showed improved membrane permeability against pure drug suspension (2.30 times) and marketed suspension formulation (1.43 times). NF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. The relative bioavailability of NFT-NE was enhanced by 1.10 and 1.17 times compared to the marketed and pure drug suspension, respectively. Thus, it can be concluded that the optimized nanoemulsion formulation of NFT exhibited improved membrane permeability, comparable cell viability, and increased relative bioavailability. These findings suggest the potential of the nanoemulsion approach as a strategy to overcome the variability of oral absorption and GI intolerance of NFT.

Natural Oils Enhance the Topical Delivery of Ketoconazole by Nanoemulgel for Fungal Infections.

Nanoemulgel (NEG) pharmaceutical formulations are gaining popularity because of their ability to serve both as a nanoemulsion and as a gel. These products are well-known for their ease of use, spreadability, controlled release, and ability to hydrate dry skin. Natural essential oils have been shown to promote the cutaneous permeability of topical formulations, enhancing medication safety and efficacy. Herein, we developed NEG for the enhanced permeation of ketoconazole against candidiasis using clove oil (clove-oil-NEG) or eucalyptus oil (eucalyptus-oil-NEG), using the gelling agents carbopol 943 and hydroxypropyl methylcellulose (HPMC). We tested various excipients to increase the solubility of ketoconazole and formulate a nanoemulsion (NE). We measured the NE droplet particle size, shape, entrapment efficiency, and drug release. Furthermore, the physicochemical properties of the optimized nanoemulsion formulation were characterized by techniques such as Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. The NEs were loaded into gels to form NEGs. NEGs were characterized for drug content, homogeneity, rheology, spreadability, and antifungal activity against Candida albicans, both in vitro and in vivo. Optimized ketoconazole NEG preparations consisted of either 15% clove oil or 20% eucalyptus oil. Droplet sizes in the optimized NEs were <100 nm, and the polydispersity indexes were 0.24 and 0.26. The percentages of ketoconazole released after 24 h from the clove-oil-NEG and eucalyptus-oil-NEGs were 91 ± 4.5 and 89 ± 7%, respectively. Scanning electron microscopy (SEM) showed that the NEGs had a smooth, uniform, and consistent shape and internal structural organization. The drug contents in the clove-oil-NEG and eucalyptus-oil-NEG were 98.5 ± 2.2 and 98.8 ± 3.4%, respectively. Permeation values of ketoconazole from clove-oil-NEG and eucalyptus-oil-NEG were 117 ± 7 and 108.34 ± 6 μg cm-2, respectively. The ketoconazole NEG formulations also had higher levels of fungal growth inhibition than a marketed formulation. Finally, in vivo studies showed that the NEGs do not irritate the skin. Ketoconazole NEG with either 15% clove oil or 20% eucalyptus oil is stable with better efficacy than ketoconazole alone due to excellent dispersion, drug dissolution, and permeability and thus might be recommended for the effective and safe treatment of candidiasis.

Optimization of Potential Nanoemulgels for Boosting Transdermal Glimepiride Delivery and Upgrading Its Anti-Diabetic Activity.

Transdermal drug delivery has been widely adopted as a plausible alternative to the oral route of administration, especially for drugs with poor systemic bioavailability. The objective of this study was to design and validate a nanoemulsion (NE) system for transdermal administration of the oral hypoglycemic drug glimepiride (GM). The NEs were prepared using peppermint/bergamot oils as the oil phase and tween 80/transcutol P as the surfactant/co-surfactant mixture (Smix). The formulations were characterized using various parameters such as globule size, zeta potential, surface morphology, in vitro drug release, drug-excipient compatibility studies, and thermodynamic stability. The optimized NE formulation was then incorporated into different gel bases and examined for gel strength, pH, viscosity, and spreadability. The selected drug-loaded nanoemulgel formulation was then screened for ex vivo permeation, skin irritation, and in vivo pharmacokinetics. Characterization studies revealed the spherical shape of NE droplets with an average size of ~80 nm and a zeta potential of -11.8 mV, which indicated good electrokinetic stability of NE. In vitro release studies revealed enhanced drug release from the NE formulation compared to the plain drug. GM-loaded nanoemulgel showed a 7-fold increment in drug transdermal flux compared to plain drug gel. In addition, the GM-loaded nanoemulgel formulation did not elicit any signs of inflammation and/or irritation on the applied skin, suggesting its safety. Most importantly, the in vivo pharmacokinetic study emphasized the potential of nanoemulgel formulation to potentiate the systemic bioavailability of GM, as manifested by a 10-fold rise in the relative bioavailability compared to control gel. Collectively, transdermal NE-based GM gel might represent a promising alternative to oral therapy in the management of diabetes.

Formulation and characterization of nanoemulsions stabilized by nonionic surfactant and their application in enhanced oil recovery

Nanoemulsions are kinetically stable emulsions with droplet size distribution in the range of 10–500 nm. Low interfacial tension (IFT), small droplet size, and wettability alteration properties of nanoemulsions have led to their application for enhanced oil recovery (EOR) EOR. The current study deals with the formulation and characterization of Tergitol 15-S-9 surfactant stabilized oil/water nanoemulsion (NE). Optimal surfactant concentration accompanied by optimal salinity determination was done by observing long-term stability. The stability of the nanoemulsions was analyzed by Turbiscan and Zeta potential analysis. The optimal nanoemulsion was characterized in terms of droplet size, rheology, wettability, miscibility, and IFT. All the prepared nanoemulsion showed particle size < 300 nm. optimized nano emulsion, that is, 0.5 wt.% surfactant +0.5 wt.% salinity showed good IFT reduction and wettability alteration capability. Nanoemulsion also showed good miscibility behavior with actual crude oil at 60 °C. Rheology of the formed emulsion shows a mixed nature that is shear thinning as well as shear thickening nature which is favorable for heterogeneous reservoirs. Core-flooding experiments were conducted at optimized nanoemulsion formulation, and additional oil recovery of 13.93% of the original oil in place was obtained after the conventional water flooding. Highlights Experimental and mechanistic investigation of nanoemulsions for oil recovery. Enhanced miscibility of Tergitol 15-S-9 stabilized nanoemulsion with crude oil. Viscosity enhancement by macromolecular and supramolecular network structures. Low IFT achieved for the nanoemulsion resulting enhanced oil displacement. Encouraging oil displacement by injection of formulated nanoemulsion.

Formulation of Aucklandiae Radix Extract-Loaded Nanoemulsions and Its Characterization and Evaluations In Vitro and In Vivo.

This study aimed to screen, design, and evaluate an optimal nanoemulsion formulation for Aucklandiae Radix extraction (ARE). A simple lattice design (SLD) method was used to determine the preparation process of Aucklandiae Radix extract-nanoemulsions (ARE-NEs). After optimization, the average particle size of ARE-NEs was 14.1 ± 1.1nm, polydispersity index was 0.2376, and pH was 6.92. In vitro penetration tests verified that the permeability ratios of costunolide (CE), dehydrocostus lactone (DE), and ARE-NEs were approximately 6.33 times and 8.20 times higher, respectively, than those of the control group. The results of the pharmacokinetic study indicated that after topical administration, the content of the index components of ARE-NEs increased in vivo, with a longer release time and higher bioavailability in vivo than in vitro. The index components were CE and DE, respectively. In addition, a skin irritation test was conducted on normal and skin-damaged rabbits, aided by HE staining and scanning electron microscopy, to reveal the transdermal mechanism of ARE-NEs and proved that NEs are safe for topical application. ARE-NEs energetically developed the properties of skin and penetration through the transdermal route, which were secure when applied via the transdermal delivery system .

Fabrication and Optimization of Essential-Oil-Loaded Nanoemulsion Using Box-Behnken Design against Staphylococos aureus and Staphylococos epidermidis Isolated from Oral Cavity.

Oral bacterial infections are fairly common in patients with diabetes mellitus; however, due to limited treatment options, herbal medicines are considered an alternate solution. This study aimed to formulate a stable essential-oil-loaded nanoemulsion for the treatment of oral bacterial infections. Essential oils from edible sources including coriander, clove, cinnamon and cardamom were extracted by hydrodistillation. The response surface methodology was used to optimize the nanoemulsion formulation by applying the Box–Behnken design. The oil concentration, surfactant concentration and stirring speed were three independent factors, and particle size and polydispersity index were two responses. The particle size, polydispersity index and zeta potential of the optimized formulation were 130 mm, 0.222 and −22.9, respectively. The ATR-FTIR analysis revealed that there was no incompatibility between the active ingredients and the excipients. A significant release profile in active ingredients of nanoemulsion, i.e., 88.75% of the cinnamaldehyde and 89.33% of eugenol, was recorded after 24 h. In the ex vivo goat mucosal permeation study, 71.67% of the cinnamaldehyde permeated and that of the eugenol 70.75% from the nanoemulsion. The optimized formulation of the essential-oil-loaded nanoemulsion showed a 9 mm zone of inhibition against Staphylococcus aureus and Staphylococcus epidermidis, whereas in anti-quorum sensing analysis, the optimized nanoemulsion formulation showed an 18 mm zone of inhibition. It was concluded that formulated essential-oil-loaded nanoemulsion can be used against S. epidermidis and S. aureus infections in oral cavity.

Thermosensitive Hydrogels Loaded with Resveratrol Nanoemulsion: Formulation Optimization by Central Composite Design and Evaluation in MCF-7 Human Breast Cancer Cell Lines.

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

Gemcitabine-Loaded Nanocarrier of Essential Oil from Pulicaria crispa: Preparation, Optimization, and In Vitro Evaluation of Anticancer Activity.

The limitations of gemcitabine (GEM) in cancer therapy are due to its poor pharmacokinetics, which cause undesired adverse effects. The current study was aimed at investigating the anticancer effect and apoptotic mechanism of synthesized nanoemulsion (NE) containing Pulicaria crispa essential oil (PC-EO) and GEM (PC-NE:GEM) on MCF-7 and Hep-G2 cancer cell lines. An optimized NE formulation was selected based on the Box–Behnken method. The droplet size of the optimized PC-NE was 9.93 ± 0.53 nm, but after GEM loading, it was increased to 11.36 ± 0.0.21 nm. Results from FTIR revealed that GEM was successfully loaded onto PC-NE. The antineoplastic effect of PC-NE:GEM on MCF-7 and Hep-G2 cancer cells was increased more than 100-fold relative to that of GEM. A combination index and isobologram based on CompuSyn software revealed the synergistic effect of the formulation produced by a 1:1 ratio combination of PC-NE and GEM. These findings were confirmed by examination of cellular morphologies. The combination formulation strongly induced about 4.48-fold and 2.95-fold increases in apoptosis in MCF-7 and Hep-G2 cells, respectively, when compared with GEM. Moreover, PC-NE:GEM produced a synergistic increase in ROS production in MCF-7 cells (15.23%) and Hep-G2 cells (31.69%), when compared with GEM. In addition, PC-NE:GEM enhanced the activation of the intrinsic apoptosis pathway through upregulation of expressions of p53 and Caspase-3, and downregulation of Bcl-2 expression in MCF-7 cells, while the expressions of Caspase-3, Bax, and p53 were upregulated in HepG2 cells. These results indicate that the GEM-loaded NE containing PC-EO may reduce the dose of GEM and eliminate the associated side effects.

Mucoadhesive meloxicam-loaded nanoemulsions: Development, characterization and nasal applicability studies

Intranasally administered non-steroidal anti-inflammatory drugs (NSAIDs) offer an innovative opportunity in the field of pain management. Combination of the nasal physiological advantages such as the rich vascularization and large absorption area along with novel nanomedical formulations can fulfill all the necessary criteria of an advanced drug delivery system. Nanoemulsions represent a versatile formulation approach suitable for nasal drug delivery by increasing the absorption and the bioavailability of many drugs for systemic and nose-to-brain delivery due to their stability, small droplet size and optimal solubilization properties. In this study we aimed to develop meloxicam (MX)-loaded mucoadhesive nanoemulsions and to investigate the nasal applicability of the optimized formulations. Our results indicated the optimized nanoemulsion formulation (MX-NE3) had a droplet size of 158.5 nm in monodisperse droplet size distribution (polydispersity index of 0.211). The surface charge was −11.2 mV, which helped with the colloidal stability upon dilution at simulated nasal conditions and storage. The high encapsulation efficiency (79.2%) mediated a 15-fold drug release and a 3-fold permeability increase at nasal conditions compared to the initial MX. Proper wetting properties associated with high mucoadhesion prosper the increased residence time on the surface of the nasal mucosa. No cytotoxic effect of the formulations was observed on NIH/3T3 mouse embryonic fibroblast cell lines, which supports the safe nasal applicability.

A nanoemulsion based transdermal delivery of insulin: Formulation development, optimization, in-vitro permeation across Strat-M® membrane and its pharmacokinetic/pharmacodynamic evaluation

Peptides and proteins are mainly delivered through the parenteral route which is painful and reduces patient compliance. The aim was to explore the feasibility of using nanoemulsion as an alternative carrier for the transdermal delivery of insulin. For this purpose, pseudoternary phase diagram was constructed to determine the exact ratio of nanoemulsion components. A Simplex lattice design was used to formulate nanoemulsion comprising of oleic acid, tween 80, isopropyl alcohol, and water as independent variables and droplet size, entrapment ratio, and flux as responses. Particle size distribution was determined through DLS and SEM. The gradient-HPLC method for the quantification of insulin was developed and validated. The in vitro permeation was carried out using Strat-M® membrane. Circular dichroism (CD), native gel electrophoresis, storage stability at 4 °C, skin irritation, pharmacokinetics, and pharmacodynamic study of optimized nanoemulsion were also performed. Optimized formulation was based on the small droplet size (41.05 ± 8 nm), maximum entrapment ratio (93.08%), and higher flux of (1.75 μg/cm2/h). The developed chromatographic method detected insulin in the range of 0.5–2.4 μg/mL. The CD spectra revealed minor changes in the secondary structure of insulin due to the entrapment in the micelles of nanoemulsion. The optimized nanoemulsion formulation was stable for three months. The PK/PD analysis indicated the slow absorption of insulin from the nanoemulsion as compared to SC injection in Albino Wister rats, resulting in delayed and consistent response having relative bioavailability of 244.5%. The results indicate that this system may be a promising vehicle for transdermal insulin delivery.

Design, Development and Characterization of Nanoemulsion developed by High Pressure Homogenization (HPH) method Containing Antifungal Drug

Nanoemulsion is one the most attractive drug delivery for researchers to treat fungal diseases and getting interested in increasing the solubility of low soluble drugs. The objective of this research was to develop a topical nanoemulsion formulation of Posaconazole drug with the intention to enhance its aqueous solubility and local action. By employing High Pressure Homogenization (HPH) method, oil in water nanoemulsion was formulated with 0.2% cinnamon oil as lipid phase, 0.4% tween-80 and poloxamer-188 as surfactants, 0.2% transcutol as a co-surfactant. The physical characteristics of formulations were found to be stable after thermodynamic stability testing. In-vitro diffusion study for optimized nanoemulsion was performed using a dialysis bag membrane and cumulative % drug release was determined. Viscosity and percent drug content was observed to be 0.0593 cps and 90.21 ± 0.23% respectively. The optimized nanoemulsion formulation (F8) was evaluated to be transparent and thermodynamically stable, with -9.46 zeta potential, 78.79 nm particle size, 0.315 polydispersity index. The optimized Nanoemulsion was stable for 3 month in three different temperature conditions. The result from the release study was indicative of improved solubility of Posaconazole, which may serve to boost up the action of the drug for the treatment of fungal diseases.&#x0D; Keywords: Posaconazole, Nanoemulsion, HPH method, Physical Characterization

The Effect of Temperature and Incubation Period on the Size and Polydispersity Index of the Nano-Emulsion Containing Essential Oil from &lt;i&gt;Cinnamomum zeylanicum &lt;/i&gt;

Nanotechnology permits broad advances in agricultural research, such as disease prevention and treatment in plants using various approaches including nano-fungicide. Nano-fungicide has been able to draw much attention due to its higher efficacy even at very low doses because nano-sized particles could be more chemically reactive and bioactive than larger particles. Nano-fungicide is defined as a nanomaterial containing an active ingredient (essential oil etc.) with fungicide action and is incorporated into nano-emulsion. Nano-emulsion is obtained when the size of an emulsion droplet reaches approximately 20-500 nm. The physicochemical properties of nano-emulsions are interesting for practical applications especially in agriculture because of their small droplet size and long-term stability. Previously, a nano-fungicide formulation was developed using the nano-emulsion composition of the detergent Span 80 and Tween 80 and the essential oil extracted from the plant leaves of Cinnamomum zeylanicum (cinnamon) was successful to control the growth of Aspergillus flavus in storage grain corn. In this study, we investigated the effect of temperature at 4°C, 30°C and 60°C on the size and polydispersity index (PDI) of the nano-emulsion droplet at day 1, 30 and 60 of storage. The results of the nano-emulsion droplet size were significantly increased at 60°C after 30 and 60 days of storage and stable from 4 to 30°C even at 60 days of storage. This study provides a strategy to evaluates the effect of environmental factors on the quality of the formulated product, which is utilized for the prediction of its shelf life and determine proper storage conditions. Therefore, the optimized nano-emulsion formulation was characterized by droplet size and PDI for 2 months.

CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Preparation of Water-in-Oil Nanoemulsions Loaded with Phenolic-Rich Olive Cake Extract Using Response Surface Methodology Approach.

In this study, we aimed to prepare stable water-in-oil (W/O) nanoemulsions loaded with a phenolic-rich aqueous phase from olive cake extract by applying the response surface methodology and using two methods: rotor-stator mixing and ultrasonic homogenization. The optimal nanoemulsion formulation was 7.4% (w/w) of olive cake extract as the dispersed phase, and 11.2% (w/w) of a surfactant mixture of polyglycerol polyricinoleate (97%) and Tween 80 (3%) in Miglyol oil as the continuous phase. Optimum results were obtained by ultrasonication for 15 min at 20% amplitude, yielding W/O nanoemulsion droplets of 104.9 ± 6.7 nm in diameter and with a polydispersity index (PDI) of 0.156 ± 0.085. Furthermore, an optimal nanoemulsion with a droplet size of 105.8 ± 10.3 nm and a PDI of 0.255 ± 0.045 was prepared using a rotor-stator mixer for 10.1 min at 20,000 rpm. High levels of retention of antioxidant activity (90.2%) and phenolics (83.1–87.2%) were reached after 30 days of storage at room temperature. Both W/O nanoemulsions showed good physical stability during this storage period.

Fluconazole and Curcumin Loaded Nanoemulsion Against Multiple Drug Resistance Dermatophytes

Purpose: Topical nanoemulsion comprising of fluconazole and curcumin was developed to target multiple drug resistance dermatophytes infection and to facilitate cutaneous delivery of these poorly water soluble drugs. Methods: Almond oil, sesame oil and paraffin light were used to formulate nanoemulsions and screened for the stability. The solubility of fluconazole and curcumin in surfactants, co-surfactants and oils was screened to decide the various components of the nanoemulsion. The oil phase was light paraffin whereas tween 80 and span 80 were the surfactants and ethanol was used as a co-surfactant. To identify the area of nanoemulsion existence, a pseudoternary diagram was drawn and optimum systems were developed. Drug-loading efficiency was assessed and the developed nanoemulsions were characterized for globule size, stability, robustness to dilution and pH. The optimized nanoemulsion was further evaluated for drug content, viscosity, skin permeation study (ex vivo) and assay of antifungal activity. Results: The globule size was below 200 nm and uniform for the optimized nanoemulsion formulation. It showed enhanced skin permeation (ex vivo) and better antifungal efficacy as compared to the native form of fluconazole and curcumin suspensions. Antimicrobial assay confirmed the synergistic effect of fluconazole and curcumin combination against multiple drug resistance Trychophytum rubrum and Trichophyton metagrophytes as compared to the fluconazole alone. Conclusion: The results clearly indicate an optimized delivery of fluconazole and curcumin in a synergistic way from the nanoemulsion formulation. This resulted in better penetration of these poorly soluble molecules and overall enhanced antifungal activity as compared to these drugs as such against multiple drug resistance dermatophytes.

Development of Topical Nanoemulgel Using Combined Therapy for Treating Psoriasis.

This study focuses on the development of topical formulation of methoxsalen using Babchi oil as formulation component that can be applied at body surfaces providing sustained delivery and enhanced penetration of methoxsalen leading to significant epidermal localization and better anti-psoriatic activity. The combination of psoralens, that is, methoxsalen (synthetic) and Babchi oil (natural) has been developed into nanoemulgel formulations. A total of four nanoemulsion formulations was developed using Babchi oil as oil phase and Tween 80 as surfactant by high-pressure homogenization method. The prepared nanoemulsions were characterized for entrapment efficiency, mean droplet size, and zeta potential. Based on characterization results, the optimized nanoemulsion formulation(s) were incorporated into the carbopol gel base to make a nanoemulgel. The prepared nanoemulgel formulations were analyzed for pH, drug content determination, spreadability, viscosity, ex vivo skin permeation, and in vivo studies. The nanoemulsions showed droplet size between 51.3 and 146.7 nm, entrapment efficiency of 92.76%-98.10%, and zeta potential of -28.1 to -54.89 mev. The nanoemulsions showed varied in vitro drug release. In ex vivo skin permeation, nanoemulgel (NG2) showed increased penetration and localized accumulation of methoxsalen across the skin compared with plain gel. Ex vivo results were substantiated by in vivo results showing significant amelioration of hyperproliferative skin symptoms. The promising results suggested that nanoemulgel system is a suitable carrier for the topical delivery of methoxsalen-Babchi oil.

NANOEMULSION FOR TOPICAL THERAPY OF ACNE: OPTIMIZATION AND EVALUATION

The present investigation was aimed / carried out to develop a nano-sized emulsion-based vehicle containing 13-cis-retinoic acid as a means of increasing its permeability and be a suitable topical therapy for acne. Various heterogeneous dispersions were formulated by spontaneous nano emulsification method using 9% w/w propylene glycol dicaprylate/dicaprate, 27% w/w caprylocaproyl macrogol glycerides, 9% w/w polyglyceryl–6–dioleate and 55% w/w distilled water as an external phase. All plain and 13- cis-retinoic acid loaded nanoemulsions were clear and showed suitable physicochemical parameters for desired topical delivery and stability. The permeation profiles of 13-cis-retinoic acid through rat skin from selected optimized nanoemulsion formulation followed zero order kinetics. The microscopic observations indicate that the optimized nanoemulsion has no significant effect on the microscopic structure of the skin and epithelial cells appeared mostly unchanged. The surface epithelium lining and the granular cellular structure of the skin were totally intact. Hence, developed nanoemulsion containing 13-cis-retinoic acid would be a potential drug delivery vehicle for effective management of acne.

Coconut oil-based resveratrol nanoemulsion: Optimization using response surface methodology, stability assessment and pharmacokinetic evaluation

Phytochemicals are widely studied for therapeutic applications and nanostructured delivery systems for phytochemicals are under spotlight. Resveratrol is a promising candidate for neurodegenerative disorders. In the present study, we aimed to formulate nanoemulsion of resveratrol by ultrasonication process using response surface methodology. The effect of both formulation and ultrasonication process factors were studied for the nanoemulsification process using coconut oil, Pluronic-P107, and Cremophor EL. The time, intensity, and power of ultrasonication were selected as process factors. The globule size, PDI, and zeta potential were the responses selected. The concentrations of oil and surfactant and the intensity were found to significantly influence the globule size. The concentration of resveratrol in the optimized nanoemulsion formulation was 2.6442 mg/ml. The in vitro drug release in pH 6.8 phosphate buffer as well as in vitro permeation study on goat nasal mucosa proved the superiority of the nanoemulsion formulation. On intranasal administration in the rat at a resveratrol dose of 2 mg/kg, the brain targeting efficacy of the nanoemulsion formulation was high. Overall, this research provides the benefit of intake of resveratrol containing fruits and, its incorporation into nanoemulsions system could be a promising alternative for the management of Alzheimer's disease.