Spontaneous Nanoemulsification Research Articles

Antimicrobial activity of nanoemulsion containing <i>Moringa oleifera</i> seed protein

Plant-based antimicrobial substances have been recognized as antimicrobial agents. These peptides demonstrate antimicrobial properties against a wide range of pathogens. This study reports the efficacy of <i>Moringa oleifera </i>nanoemulsion as an antimicrobial. <i>M. oleifera </i>seed was defatted and the protein was extracted from the grounded seed, characterized, and formulated into nanoemulsions by spontaneous nanoemulsification. This method is economically and environmentally safe as the components of nanoemulsion are biodegradable. The formulation was evaluated for particle size, viscosity, pH, antimicrobial activity, and kill time assay. The nanoemulsion was nanosized (43.440 nm - 74.430 nm) with increased encapsulation efficiency in a dose-dependent manner and a suitable pH (5.91 ± 0.01 to 6.14 ± 0.01), excellent dynamic viscosity (32 ± 7 to 39 ± 0). The antimicrobial and minimum inhibitory concentration study displayed a wide range of effectiveness on <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>, the time-kill assay showed moderate biocidal activity. Therefore, <i>M. oleifera </i>seed protein nanoemulsion has the potential to act as antimicrobial.

Preparation and In vitro/Ex vivo Evaluation of Nanoemulsion-Based in Situ Gel for Intranasal Delivery of Lasmiditan

Lasmiditan (LAS) was formulated as a nanoemulsion based in situ gel (NEIG)with the aim of improving its oral bioavailability via application intranasally. The solubility of LAS in oils, emulsifiers, and co-emulsifiers was determined to identify nanoemulsion (NE)components. Phase diagrams were constructed to identify the area of nanoemulsification. LAS NE was formulated using the spontaneous nanoemulsification method. Four NEs (F19, F24, F31, and F34) containing 7-15 % oleic acid (OA) as an oily phase, 40-55% labrasol (LR), and transcutol (TC) as emulsifier mixture at (1:1), (2:1), (3:1), and (1:2) ratio with 30-53 % (w/w) aqueous phase, having suitable optical transparency of 95–98%, globule size of 104-140 nm and polydispersity of 0.253–0.382 were selected for ex vivo permeation study. F31 with the highest flux value (2.32 ± 0.01 mg/cm2.min) relative to the other NEs. It achieves an enhancement ratio of 3.3 as compared to LAS aqueous suspension (8% LAS) also it achieves a significantly higher value of permeability coefficient. F31 was selected for the incorporation of different percentages of pH-sensitive in situ gelling polymer (Carbopol 934) to prepare NEIGs 4,5 and 6. The gel strength, pH, gelation time, and viscosity were predicted for the prepared NEIGs. In vitro release and ex vivo, nasal permeation were determined for NEIG5, which exerts comparable release and permeation values as F31 with more residence time in order to overcome the normal nasal physiological clearance.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

Transdermal delivery and exploration of preclinical anti-rheumatoid efficacy of pirfenidone embedded nanoemulgel in adjuvant-induced rat model

To avoid adverse effects associated with non-site-specific delivery and target major signaling pathways responsible for the inflammation in rheumatoid arthritis, the current study aims to formulate and evaluate the transdermally administered potential of pirfenidone nanoemulgel in rheumatoid arthritis. The pirfenidone was initially loaded into nanoemulsion by spontaneous nanoemulsification method. The optimized pirfenidone-loaded nanoemulsion diluted with distilled water has shown a droplet size of 9.46 ± 0.01 nm with uniform size distribution evaluated by photon correlation spectroscopy. The optimized pirfenidone nanoemulsion was converted into gel formulation by adding SEPINEO™ P600 gel base with the help of magnetic stirring. The optimized pirfenidone-loaded nanoemulgel has shown a viscosity of 769 ± 05 Pa s with an antigravity nature. Ex vivo permeation study of pirfenidone nanoemulgel in BALB/c mice skin resulted in 1.7 times higher permeation of pirfenidone than free pirfenidone loaded gel. The preclinical efficacy of pirfenidone-loaded nanoemulgel has shown promising results in the rheumatoid arthritis-induced rat model. The right hind paw thickness (##p < 0.01) and arthritis severity score (####p < 0.0001) in pirfenidone nanoemulgel treated group resulted in significant reduction than negative control on 25th day of study. The spleen (****p < 0.0001) and liver indices (**p < 0.01) in rat group treated with pirfenidone nanoemulgel were found to be significantly reduced than negative control. The serum levels of IL-1β (***p < 0.001) and IL-6 (**p < 0.01) were significantly decreased in the pirfenidone nanoemulgel treated group compared to negative control evaluated using enzyme linked immunosorbent assay. The radiographic images of pirfenidone nanoemulgel treated group showed reduction in swelling of soft tissue and bone erosion than negative control. The examination of the hind paw showed improved condition of paw joint with increased synovial space, reduction in the cellular infiltrates and decrease in the swelling of the joints in the pirfenidone nanoemulgel treated group.

Spontaneous nanoemulsification of cinnamon essential oil: Formulation, characterization, and antibacterial and antibiofilm activity against fish spoilage caused by Serratia rubidaea BFMO8.

The contemporary food industry's uses of nanoemulsions (NEs) include food processing, effective nutraceutical delivery, the development of functional chemicals, and the synthesis of natural preservatives, such as phytocompounds. Although cinnamon essential oil (CEO) is widely used in the cosmetic, pharmaceutical, and food industries, it is difficult to add to aqueous-based food formulations due to its weak stability and poor water solubility. This study describes the formulation of a CEO nanoemulsion (CEONE) by spontaneous emulsification and evaluates its antibacterial and antibiofilm properties against biofilm-forming Serratia rubidaea BFMO8 isolated from spoiled emperor fish (Lethrinus miniatus). Bacteria causing spoilage in emperor fish were isolated and identified as S. rubidaea using common morphological, cultural, and 16S RNA sequencing methods, and their ability to form biofilms and their susceptibility to CEONE were assessed using biofilm-specific methods. The spontaneous emulsification formulation of CEONE was accomplished using water and Tween 20 surfactant by manipulating organic and aqueous phase interface properties and controlling particle growth by capping surfactant increases. The best emulsification, with highly stable nano-size droplets, was accomplished at 750rpm and a 1:3 ratio concentration. The stable CEONE droplet size, polydispersity index, and zeta potential values were 204.8nm, 0.115, and -6.05mV, respectively. FTIR and high-resolution liquid chromatography-mass spectrometry (HR-LCMS) analyses have revealed carboxyl, carbonyl, and phenol-like primary phytochemical functional groups in CEO and CEONE, which contribute to their antibacterial and antibiofilm properties.

Radiopaque Iodosilane-Coated Lipid Hybrid Nanoparticle Contrast Agent for Dual-Modality Ultrasound and X-ray Bioimaging.

Here, we report the synthesis of robust hybrid iodinated silica-lipid nanoemulsions (HSLNEs) for use as a contrast agent for ultrasound and X-ray applications. We engineered iodinated silica nanoparticles (SNPs), lipid nanoemulsions, and a series of HSLNEs by a low-energy spontaneous nanoemulsification process. The formation of a silica shell requires sonication to hydrolyze and polymerize/condensate the iodomethyltrimethoxysilane at the oil/water interface of the nanoemulsion droplets. The resulting nanoemulsions (NEs) exhibited a homogeneous spherical morphology under transmission electron microscopy. The particles had diameters ranging from 20 to 120 nm with both negative and positive surface charges in the absence and presence of cetyltrimethylammonium bromide (CTAB), respectively. Unlike CTAB-coated nanoformulations, the CTAB-free NEs showed excellent biocompatibility in murine RAW macrophages and human U87-MG cell lines in vitro. The maximum tolerated dose assessment was evaluated to verify their safety profiles in vivo. In vitro X-ray and ultrasound imaging and in vivo computed tomography were used to monitor both iodinated SNPs and HSLNEs, validating their significant contrast-enhancing properties and suggesting their potential as dual-modality clinical agents in the future.

FORMULATION AND CHARACTERIZATION OF ZEAXANTHIN NANOEMULSION RADIANCE SERUM AS ANTIOXIDANT

Objective: This study aimed to increase the effectiveness of using zeaxanthin by developed nanoemulsion containing zeaxanthin which was then formulated into radiance serum for topical use.&#x0D; Methods: Nanoemulsions are made using spontaneous nano emulsification methods/techniques, which are relatively simple technologically because they rely on the right combination of selected surfactants and co-surfactants. The optimization of the formula was carried out starting from determining the oil: surfactant: co-surfactant phase ratio and concentration of zeaxanthin. Nanoemulsion characterization in the form of physical characterization includes organoleptic tests, globule size and polydispersity index, zeta potential, pH and entrapment efficiency tests. The best results from nanoemulsion were then combined into serum preparations which were then tested for evaluation of the preparations, including organoleptic, homogeneity, viscosity, pH, spreadability, and antioxidant test.&#x0D; Results: The results showed that the developed zeaxanthin nanoemulsion had a globule size in the range of 20-24 nm (with a normal globule size distribution curve), polydispersity index value of less than 0.3, zeta potential greater than (-20) mV and entrapment efficiency ranging from 80-85%.&#x0D; Conclusion: The results of the evaluation showed that the serum radiance of zeaxanthin nanoemulsion had good physical, chemical and stability properties during storage with an IC50 value of zeaxanthin less than 50 ppm.

Oregano oil-nanoemulsions: Formulation and evaluation of antibacterial and anticancer potentials

Oregano essential oil (EO) has diverse biological activities. However, its instability and hydrophobic nature limit its incorporation in pharmaceutical preparations. The present study aimed to develop a stable oregano EO nanoemulsion (ONE) and assess its antibacterial and anticancer effects compared to free (OEO) and coarse emulsion (OE) forms. Oregano EO was hydro-distilled and analysed via Gas chromatography-Mass spectroscopy and carvacrol (65.24%) and linalool (12.32%) were the major oil constituents. EO-based nanoemulsions were prepared using spontaneous nano-emulsification and ultrasonication at different time intervals. The nanoemulsion with a droplet size of 88.37 ± 1.004 nm (0.104 ± 0.002 PDI) exhibited the best stability profile. ONE exhibited antibacterial activity against all the tested bacterial strains except Pseudomonas aeruginosa, and its activity was relatively higher against Staphylococcus epidermidis, Enterococcus faecalis and Escherichia coli than OE. Nanoemulsion demonstrated a significant reduction of IC50 values in A549 and MDA-MB-231 cell lines compared to OE and free EO. Additionally, ONE significantly inhibited colony formation and migratory abilities in both cell lines compared to OE and OEO. Moreover, a significant upregulation of the apoptotic markers CASP8 and BAX was demonstrated. A significant downregulation of antiapoptotic BCL2 and proliferation markers KI67 was also observed. To the best of our knowledge, this study is the first to scrutinize the anticancer effects of oregano oil nanoemulsion compared to conventional emulsion and free oil. Conclusively, the presently developed nanoemulsion is a promising nanoplatform for oregano EO as a potential antimicrobial and anticancer agent.

Self-nanoemulsifying drug delivery system (SNEDDS) improves the oral bioavailability of betulinic acid

Betulinic acid (BA) is a bioactive molecule with antineoplastic, antiviral, anti-inflammatory features; however, it exhibits low solubility in water, which limits its practical applications. Our work aims to develop self-nanoemulsifying drug delivery systems (SNEDDS) to improve the bioavailability of BA. We found that the oil phases containing Lauroglycol FCC and caprylic acid solubilized the greatest amount of the bioactive with 15.8 ± 0.089 and 16.019 ± 0.11 mg/mL, respectively. Pseudoternary phase diagrams were prepared to determine the spontaneous nanoemulsification zone of the systems, using Cremophor EL® and Labrafil M1944CS® as surfactants. Nanoemulsions with particle sizes ranging from approximately ca. 22 to 56 nm and polydispersity indices of 0.058–0.135 were obtained. The SNEDDS were subjected to in vitro gastrointestinal conditions, where the particle size of the nanosystems remained constant up to 105 min of simulated small intestine phase conditions. The in vivo study in a Wistar rat model demonstrated up to a 15-fold increase in BA bioavailability when administered in SNEDDS, compared to free BA.

Study of the spontaneous nano-emulsification process with different octadecyl succinic anhydride derivatives

Three new amphiphilic molecules were synthetized on a basis of a common monomer, octadecyl succinic anhydride (OSA), on which were grafted different PEGylated hydrophilic polar head. The objective of this study is to investigate a potential relationship between the chemical structure of the surfactant, and the efficiency to generate nano-emulsions through the spontaneous nano-emulsification method. Beyond the innovative synthesis and comparison of these amphiphiles, a comprehensive comparison is suggested, comparing size distribution and polydispersity for the different composition parameters, as well making a bridge with critical micelle concentration and hydrophile lipophile balance (HLB). Using OSA monomeric entity as common hydrophobic moiety, the variations in the surfactant molecules were done on the hydrophilic moiety, through the addition of one or two Jeffamine chains in different configurations, so-called C18⊖-PEG, C18-PEG and C18-PEG2. The results disclosed that C18⊖-PEG allows producing smallest size distribution and lowest PDI values. Moreover, C18⊖-PEG presents the highest critical micellar concentration, linked to a higher hydrophilicity of the molecule. This impacts the balance between surfactant affinity for oil and aqueous phases, a point probably related to the spontaneous emulsification efficiency. A last part of the study regarded the optimization of the emulsification efficiency, through a systematic study in ternary composition map, to disclosed that the best conditions are included in the lower surfactant concentrations, for water and oil contents higher and lower than 50%, respectively. The main idea behind this study was to bring further insights into the unclear relationship between the chemical structure of nonionic surfactants, and the efficiency of the emulsification by spontaneous low-energy method.

Water-in-Oil Nano-Emulsions Prepared by Spontaneous Emulsification: New Insights on the Formulation Process.

Nano-emulsions consist of stable suspensions of nano-scaled droplets that have huge loading capacities and are formulated with safe compounds. For these reasons, a large number of studies have described the potential uses of nano-emulsions, focusing on various aspects such as formulation processes, loading capabilities, and surface modifications. These studies typically concern direct nano-emulsions (i.e., oil-in-water), whereas studies on reverse nano-emulsions (i.e., water-in-oil) remain anecdotal. However, reverse nano-emulsion technology is very promising (e.g., as an alternative to liposome technology) for the development of drug delivery systems that encapsulate hydrophilic compounds within double droplets. The spontaneous emulsification process has the added advantages of optimization of the energetic yield, potential for industrial scale-up, improved loading capabilities, and preservation of fragile compounds targeted for encapsulation. In this study, we propose a detailed investigation of the processes and formulation parameters involved in the spontaneous nano-emulsification that produces water-in-oil nano-emulsions. The following details were addressed: (i) the order of mixing of the different compounds (method A and method B), (ii) mixing rates, (iii) amount of surfactants, (iv) type and mixture of surfactants, (v) amount of dispersed phase, and (vi) influence of the nature of the oil. The results emphasized the effects of the formulation parameters (e.g., the volume fraction of the dispersed phase, nature or concentration of surfactant, or nature of the oil) on the nature and properties of the nano-emulsions formed.

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.

Investigation of the spontaneous nanoemulsification process with medium- and long-chain triglycerides

Oil-in-water nanoemulsions are used in numerous biomedical applications as delivery systems. The droplet size in the nanometer range and their composition were extensively developed for carrying and enhancing the absorption of lipophilic drugs and lipids of interest. In the present study, critical parameters involved in the spontaneous nanoemulsification process such as the temperature, the oil type, the surfactant-to-oil and water-to-oil ratios were investigated. The aim was to design a solvent-free procedure for the spontaneous nanoemulsification at a low temperature of a large variety of triglycerides including vegetable oils. Nanoemulsification of medium-chain triglyceride (MCT) was not dependent on the temperature while nanodroplets of long-chain triglycerides (LCT) were only obtained by reaching the cloud point of ethoxylated surfactant Kolliphor® HS15. The molar volume of triglycerides was considered as a predictive parameter governing both, the spontaneous nanoemulsification at low temperature and the Ostwald ripening rate. The physical mixture of MCT and LCT was a promising strategy to prepare stable and fine nanoemulsions at 37 °C. They were characterized by a hydrodynamic diameter comprised between 20 and 30 nm and a narrow size distribution. These findings pave the way to new applications for the parenteral nutrition and the delivery of thermosensitive drugs and lipophilic molecules such as antioxidants.

Formulation design and pharmacokinetic evaluation of docosahexaenoic acid containing self-nanoemulsifying drug delivery system for oral administration

Docosahexaenoic acid is a omega-3-fatty acid which together with other long-chain omega-3-fatty acid known to have protective effect against various diseases including hypertension, myocardial infarction, Alzheimer disease, and cancers. Poor bioavailability owning to limited aqueous solubility limits its effective therapeutic delivery. Self-nanoemulsifying drug delivery systems are known to enhance the systemic absorption of poorly bioavailable lipophilic bioactive/therapeutics compounds. The purpose of this work was to investigate the potential of self-nanoemulsifying drug delivery systems produced by spontaneous nanoemulsification to enhance the oral bioavailability of docosahexaenoic acid. Initially, the screening of oil, surfactant, and cosurfactant was carried out by determining the miscibility and emulsifiability of the component with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems were prepared using Capryol 90, Tween 20, and polyethylene glycol 200 due to their excellent miscibility and emulsifiability with docosahexaenoic acid. Docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems’ droplet size, size distribution, and zeta potential were found to be 111.5 ± 4.2 nm, 0.269 ± 0.05 nm, and −23.53 ± 2.9 mV, respectively. The in vitro drug release and ex vivo absorption studies showed better in vitro release and intestinal absorption as compared to docosahexaenoic acid aqueous dispersion. In vivo studies demonstrated a significant increase ( p &lt; 0.001) in the oral bioavailability of docosahexaenoic acid-containing self-nanoemulsifying drug delivery systems in comparison to a docosahexaenoic acid aqueous dispersion. This indicated the potential of self-nanoemulsifying drug delivery systems as an effective unit dosage form for the oral delivery of docosahexaenoic acid.

Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier

This work was aimed at the production and characterization of a new nanocarrier based on a Sterculia striata polysaccharide (SSP) modified via acylation reaction with propionic anhydride. Nanocapsules of propionated SSP (PSSP) were produced via spontaneous nanoemulsification process and tested as a potential amphotericin B (AMB) nanocarrier. Stable nanoparticles with a very low polydispersity index (0.08–0.29) and high zeta potential (ζ −42.7 to −53.8 mV) were obtained. Particle size was dependent on the degree of substitution and ranged from 205 to 286 nm. A nanocapsule with a degree of substitution (DS) of 2.53 (NCP 2.53) was selected for encapsulation, biocompatibility, and antifungal evaluation against Candida albicans strains. A maximum of 98.3% AMB encapsulation was achieved. Encapsulated AMB was in its monomeric form and showed good biocompatibility and antifungal activity against four C. albicans strains. Data indicate that PSSP has potential as a nanocarrier system for AMB.

Spontaneous nano-emulsification with tailor-made amphiphilic polymers and related monomers

In general, nano-emulsions are submicron droplets composed of liquid oil phase dispersed in liquid aqueous bulk phase. They are stable and very powerful systems when it regards the encapsulation of lipophilic compounds and their dispersion in aqueous medium. On the other hand, when the properties of the nano-emulsions aim to be modified, e.g. for changing their surface properties, decorating the droplets with targeting ligands, or modifying the surface charge, the dynamic liquid / liquid interfaces make it relatively challenging. In this study, we have explored the development of nano-emulsions which were not anymore stabilized with a classical low-molecular weight surfactant, but instead, with an amphiphilic polymer based on poly(maleic anhydride-alt-1-octadecene) (PMAO) and Jeffamine®, a hydrophilic amino-terminated PPG/PEG copolymer. Using a polymer as stabilizer is a potential solution for the nano-emulsion functionalization, ensuring the droplet stabilization as well as being a platform for the droplet decoration with ligands (for instance after addition of function groups in the terminations of the chains). The main idea of the present work was to understand if the spontaneous emulsification –commonly performed with nonionic surfactants– can be transposed with amphiphilic polymers, and a secondary objective was to identify the main parameters impacting on the process. PMAO was modified with two different Jeffamine®, additionally different oils and different formulation conditions were evaluated. As a control, the parent monomer, octadecyl succinic anhydride (OSA) was also modified and studied in the similar way as that of polymer. The generated nano-emulsions were mainly studied by dynamic light scattering and electron microscopy, that allows discriminating the crucial parameters in the spontaneous process, originally conducted with polymers as only stabilizer.

Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion’s size and polydispersity

The aim of the present study was to optimize the size and polydispersity of a lipid nanoemulsion as a function of the oil (Labrafac® WL1349), surfactant (Kolliphor® HS 15) and cosurfactant (Span® 80) phase composition and temperature. The nanoemulsions were prepared using a low-energy self-emulsification method. The Z-average diameter and the polydispersity index (PDI) were modeled with mixture experiments. Nanoemulsions from 20 nm to 120 nm with PDI < 0.2 were obtained at the three different tested temperatures (30 °C, 50 °C and 90 °C). The nanoemulsion size was able to be controlled with the oil, surfactant and cosurfactant concentrations. Interestingly, the smallest PDIs were obtained at 30 °C, and the cosurfactant concentration was able to be adjusted to optimize the formulation and to obtain nanoemulsions in the 20–120 nm range with a PDI smaller than 0.14. These nanoemulsions have shown a good stability at 4 °C in storage conditions and at 37 °C in diluted conditions.

Nanoemulsion as a novel carrier system for improvement of betulinic acid oral bioavailability and hepatoprotective activity

Betulinic acid (BA) is a potent bioactive compound and well known for its therapeutic activity. However, its efficacy is restricted due to low solubility as well as poor bioavailability. The aim of the study was to develop a BA loaded nanoemulsions for enhanced bioavailability and hepatoprotective activity. The optimized nanoemulsion (BA-NE1) was composed of olive oil, aqueous phase and Smix [surfactant (labrasol) and co-surfactant (plurol isostearate)] in an appropriate ratio of 20:25:55% w/w respectively. BA-NE1 was prepared by spontaneous nano-emulsification method. The BA-NE1 was characterized through different parameters including droplet size, zeta potential, refractive index, transmission electron microscopy, UV-spectrophotometry, Fourier transform infrared spectroscopy and stability study. The appropriate droplet size (150.3±0.56nm) and zeta potential (−10.2±0.11mV) were observed for BA-NE1. The improved pharmacokinetics parameters Cmax (96.29±1.96ngmL−1), AUC0-t∞ (2540.35±278.31nghmL−1), Tmax (12.32±0.05h), elimination half-life (11.35±3.20h) and relative bioavailability (440.48%F) were significantly achieved with BA-NE1 compared to BA. The BA-NE1 significantly restored the levels of serum hepatic markers and hepatic antioxidant enzymes with respect to CCl4-intoxicated groups (⁎⁎p<0.05 and ⁎⁎⁎p<0.01). Therefore, the present study suggests that BA loaded nanoemulsion may enhance the hepatoprotective activity which may be due to its increased solubility as well as improved oral bioavailability.

Development and evaluation of self–nanoemulsifying drug delivery system of rhubarb anthraquinones

Rhubarb anthraquinones (RhA) as a group were formulated in nanoemulsion based system with the aim of improving its solubility and oral bioavailability. RhA loaded nanoemulsion (RhA–NE) was prepared using spontaneous nanoemulsification method. Solubility of RhA in oils, surfactants and co–surfactants was determined to select nanoemulsion components. Surfactants and co–surfactants were screened for their ability to emulsify selected oily phase. Pseudo–ternary phase diagrams were constructed to identify area of nanoemulsification. A four–factor–five–level central composite design was carried out to attain optimal formulation. The optimized formulations of RhA–NE consisted of capryol 90/ethyl oleate containing RhA as oil phase, cremophor RH 40 as surfactant, transcutol HP as co–surfactant, oleic acid as stabilizer and distilled water as water phase. The RhA–NE was characterized by dynamic light scanning, transmission electron microscope, solubilizing capacity, encapsulation efficiency, drug loading and stability. The optimized RhA–NE can obviously enhance solubilization of RhA in distilled water. The appearance and RhA contents were basically unchanged after 60-day storage at room temperature in brown bottle. More than 50% RhA released from nanoemulsion within 240 h in vitro. Pharmacokinetics in rats showed that the Cmax and AUC of RhA–NE were enhanced compared to that of RhA suspension.

Enhancement of photoprotection potential of catechin loaded nanoemulsion gel against UVA induced oxidative stress

The present study was aimed to develop a catechin (CA) loaded nanoemulsion based nano-gel for the protection of skin against ultraviolet radiation (UV) induced photo-damage and to ensure its enhanced skin permeability as well as bioavailability through transdermal route. The optimized nanoemulsion (CA-NE4) was prepared by spontaneous nano-emulsification method. It was composed of oil (ethyl oleate), Smix [surfactant (span 80) and co-surfactant (transcutol CG)] and aqueous system in an appropriate ratio of 15:62:23% w/w respectively. The CA-NE4 was characterized through assessment of droplet size, zeta potential, refractive index, transmission electron microscopy (TEM), UV, high performance thin layer chromatography (HPTLC) and Fourier transform infrared spectroscopy (FTIR) analysis. The average droplet size and zeta potential of CA-NE4 were found to be 98.6±1.01nm and −27.3±0.20mV respectively. The enhanced skin permeability was better with CA-NE4 based nano-gel (CA-NG4) [96.62%] compared to conventional gel (CA-CG) [53.01%] for a period of 24h. The enhanced % relative bioavailability (F) of CA (894.73), Cmax (93.79±6.19ngmL−1), AUC0−t∞ (2653.99±515.02nghmL−1) and Tmax (12.05±0.02h) was significantly obtained with CA-NG4 as compared to oral suspension for extended periods (72h). CA-NG4 could improve the level of cutaneous antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) and reduce the level of thiobarbituric acid reactive substances (TBRAS) against oxidative stress induced by UVA. Nano-gel formulation of CA showed sustained release profile and enhanced photoprotection potential due to its improved permeability as well as bioavailability (P<0.05) compared to the conventional gel. Therefore, transdermal administration of nano-gel (CA-NG4) of CA offers a better way to develop the endogenous cutaneous protection system and thus could be an effective strategy for decreasing UV-induced oxidative damage in the skin tissues.