Spontaneous Emulsification Method Research Articles

Hesperidin-loaded nanoemulsions improve cytotoxicity, induce apoptosis, and downregulate miR-21 and miR-155 expression in MCF-7

Hesperidin, a ubiquitous plant-based flavanone, was encapsulated into nanoemulsions (HP-NEM) using a spontaneous emulsification method to improve its solubility and enhance bioavailability and efficacy in breast cancer treatment using MCF-7 cell lines. The cytotoxic and apoptotic effects of HP-NEM against MCF-7 and its impact on oncomiRs, microRNA-21, and microRNA-155 expression were also assessed. The optimised HP-NEM displayed a spherical shape with 305 ± 40.8 nm, 0.308 ± 0.04, and −11.6 ± 3.30 mV and 93 ± 0.45% for particle size, polydispersity index (PDI), zeta-potential (ζ), and encapsulation efficiency, respectively. Cytotoxicity studies using MTT assay showed selective toxicity of the HP-NEM against MCF-7 without affecting normal cells (HEK 293). Treatment with the HP-NEM induced cell death through apoptosis, cell cycle arrest in the G2/M phase, and downregulated miR-21 and miR-155 expression in MCF-7. This study supports the use of HP-NEM as a potential therapeutic agent in breast cancer treatment.

FORMULATION AND EVALUATION OF TOPICAL NANOEMULGEL OF METHOTREXATE FOR RHEUMATOID ARTHRITIS

Objective: The purpose of this study was to develop and evaluate methotrexate-loaded nanoemulgel for topical delivery in the management of rheumatoid arthritis.
 Methods: Based on nanoemulsion composition, the pseudo ternary phase diagram was fabricated by using peanut oil, Tween 20 as the surfactant, and PEG 400 being used as a co-surfactant. The methotrexate-loaded nanoemulsion was formulated by using the spontaneous emulsification method. Badam gum was used as a gel matrix in the prepared nanoemulsion to form nanoemulgel. The methotrexate loaded nanoemulgel was characterized and evaluated for pH, particle size, physical appearance, viscosity, spreadability, TEM, drug content, diffusion study, release kinetics, and stability studies.
 Results: The nanoemulgel constituting 8.6% peanut oil, 34.4% of Tween 20 and PEG 400 as Smix (surfactant and co-surfactant mixture), 43% water, and 12.5% w/w badam gum was concluded as optimized formulation. The prepared nanoemulgel was translucent in nature having a particle size of 195.1nm and zeta potential of -0.278mV. Drug content and drug release for the optimized formulation were found to be 98.11±0.34% and 95.11±0.02% respectively. pH, viscosity, and spreadability were found to be optimum. Stability study data showed that the prepared nanoemulgel was stable at different temperatures varying from -25 to +45ºC.
 Conclusion: Methotrexate loaded nanoemulgel has been formulated for topical drug delivery for the management of rheumatoid arthritis.

Development and Evaluation of Nanoemulsions for Phenytoin Drug Loading

Aims: To understand about the nanoemulsion types and the process formation of spontaneous emulsification method by phase inversion. Then to test the different combinations of Oil, Surfactants and Co-surfactants for formation of suitable nanoemulsions for phenytoin drug loading.
 Study Design: Spontaneous emulsification method by phase inversion used to form the nanoemulsions.
 Place and Duration of Study: Department of Pharmaceutical Sciences, Kumaun University, Nainital, Uttarakhand, India.
 Methodology: Phenytoin is a widely used drug in anticonvulsants class for epilepsy which comes under BCS Class II of drug category. Phenytoin has high permeability property but it also shows low solubility property which makes it difficult to absorb from GI tract hence make a poor penetration into the brain to target disease in the CNS. To overcome the situation of poor delivery of phenytoin, the requirement of nanoparticulate drug delivery as an innovative and effective drug delivery system from nose to brain raised. The objective of our study was to find the best combination of oil and Smix (surfactant and co-surfactant mixture) to form o/w (Oil in Water) nanoemulsions suitable for loading phenytoin drug using spontaneous emulsification method for brain targeting.
 Results: Based on different compositions of oil (sunflower), surfactants (Tween-20), and co-surfactants (Transcutol P), forty-five test mixtures were made, water titration technique was employed for preparing the pseudo-ternary-phase diagrams. On the basis of these phase diagrams twenty-five phenytoin loaded nanoemulsions were formulated and further examined. After physicochemical characterization of these formulations the viscosity, pH, RI and % transmittance was found (6.149 ± 0.084 to 9.114 ± 0.027), (6.546 ± 0.018 to 6.656 ± 0.017), (1.395 ± 0.003 to 1.41 ± 0.005) and (94.53 ± 1.4% to 95.58 ± 1.2%) respectively. The release rate of phenytoin was found very satisfactory i.e., 98.51 ± 0.25 % to 99.82 ± 0.28 % after 24 hrs. The four formulations showed best release rate had further taken for particle size analysis. The particle size analysis showed that all the properties were in the desired range i.e., droplet size (18.9 to 21.9), zeta potential (-12.4 to -28.8), PDI (0.334 to 0.363). The study shows that the phenytoin loaded nanoemulsion is possible to make by water titration method and shall have a good drug release rate.
 Conclusion: The nanoemulsion formulations passed through stress testing had also showed good release rate of phenytoin. Also, the other parameters like viscosity, pH, RI and percentage transmittance were in a quit satisfactory range to proceed further with these formulations. The particle size analysis confirms the formation of nanoemultions which had very good drug release rates.

Nanovaccine for Plants from Organic Waste: d-Limonene-Loaded Chitosan Nanocarriers Protect Plants against Botrytis cinerea

Chitosan and d-limonene are bioactive molecules derived from organic waste. We repurposed them in the form of a drug delivery system for agricultural applications in crop protection to combatBotrytis cinerea, a broad host-range necrotrophic (BHN) pathogen that causes economic losses worldwide. Synthetic fungicide application remains the most common method to control this pathogen, but this comes with a significant environmental cost. Drug delivery systems from naturally occurring biomaterials can offer efficient treatment options to combat this pathogen. We hypothesized that engineered chitosan nanoparticles (CSNPs) loaded with d-limonene can trigger an on-demand systemic defense response in plants that enhances its quantitative disease resistance against BHN. Chitosan nanocarriers encapsulated with d-limonene as cargo were fabricated through a rational formulation via ionic gelation and the spontaneous emulsification method, respectively, to produce chitosan d-limonene nanoparticles (CdlNPs). The therapeutic effect of the d-limonene nanoemulsion, CSNPs, and CdlNPs on the plants’ defense response against necrotrophic fungal pathogens was evaluated by monitoring the dynamic morpho-physiological changes via multispectral image-based phenotyping in an Arabidopsis thaliana (Col-0)–B. cinerea model system. Functional analysis of the differentially expressed genes revealed that at the concentration of significant disease resistance (0.5%), CSNPs downregulated the biological process involved in plant growth and development, but upregulated the main process controlling response to stress.

DEVELOPMENT AND IN VITRO ASSESSMENT OF BUSPIRONE LOADED IN SITU NANOEMULSION GEL

Objective: Buspirone, is a medication primarily used for generalized anxiety disorder (GAD), relieve symptoms of anxiety and unipolar depression. This drug exhibit low bioavailability (approximately 5%) due to extensive first-pass metabolism and non-targeted delivery results in numerous side effects. It is taken by mouth, and it may take up to four weeks to have an effect. The present investigation aimed at the development of buspirone in situ nanoemulsion gel to evaluate its potential for efficacious nose to brain drug delivery.
 Methods: Buspirone-loaded nanoemulsions (BNEs) were prepared by aqueous titration (Spontaneous emulsification) method using Oleic acid, Tween 80, and PEG 400 as oil, surfactant and cosurfactant respectively. The NEs (FC1-FC8) were characterized for pharmaceutical characteristics (Appearance, thermodynamic stability, polydispersity index (PDI) value, globule size, pH, Viscosity, Conductivity and Refractive index). In vitro drug release study from nanoemulsions (NEs) was carried out using Keshary–Chien cell (KC cell, 25 ml) in phosphate buffer pH 5.5.
 Results: Formulation FC5 with mean globule size of 105.4±1.10 nm, PDI value 0.230±0.01 and drug release 90±0.39% in 6 h (h) was developed as mucoadhesive nanoemulsion gel formulation with 17.5 % W/W of Pluronic F127. The nanoemulsion gel was homogenous, transparent, and possessed a bioadhesive strength of 1605 Dyne/cm2. In vitro cumulative drug release was found to be 90.00±0.39 % at the end of 6 h.
 Conclusion: The gel had no effect on the structural integrity of nasal mucosa. Hence, the study postulates that In situ nanoemulsion gel of buspirone could be used as an intranasal formulation for targeted brain delivery via nasal route.

Cineole-containing nanoemulsion: Development, stability, and antibacterial activity

1,8-cineole is a monoterpene commonly used by the food, cosmetic, and pharmaceutical industries owing to its flavor and fragrances properties. In addition, this bioactive monoterpene has demonstrated bactericidal and fungicidal activities. However, such activities are limited due to its low aqueous solubility and stability. This study aimed to develop nanoemulsion containing cineole and assess its stability and antibacterial activity in this context. The spontaneous emulsification method was used to prepare nanoemulsion (NE) formulations (F1, F2, F3, F4, and F5). Following the development of NE formulations, we chose the F1 formulation that presented an average droplet size (in diameter) of about 100 nm with narrow size distribution (PdI <0.2) and negative zeta potential (∼ – 35 mV). According to the analytical centrifugation method with photometric detection, F1 and F5 formulations were considered the most stable NE with lower droplet migration velocities. In addition, F1 formulation showed high incorporation efficiency (> 80 %) and TEM analyses demonstrated nanosized oil droplets with irregular spherical shapes and without any aggregation tendency. Antibacterial activity assessment showed that F1 NE was able to enhance the cineole action against Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes. Therefore, using a simple and reproducible method of low energy emulsification we designed a stable nanoemulsion containing 1,8-cineole with improved antibacterial activity against Gram-positive strains.

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.

Spontaneous emulsification induced by a novel surfactant-polymer compound system and its application to enhance oil recovery

The application of spontaneous emulsification method during oil displacement provides a low-cost and environmentally friendly approach to enhance oil recovery for unconventional reservoirs. A surfactant-polymer mixture system composed of hydrophobically modified polyvinyl alcohol (HPVA) and cetyltrimethylammonium bromide (CTAB) with the ability of spontaneous emulsification was constructed. The optimum formulation of HPVA/CTAB compound system was selected based on the spontaneous emulsification capability and emulsion stability. It is found that the system showed best spontaneous emulsification performance with the concentration of 3000 mg/L and the mass ratio of 7:3 (HPVA:CTAB). The dynamic interfacial tension between oil and water reached ultra-low level to promote oil dispersing into water spontaneously, then rose back to low level to keep the emulsion stable. The synergistic effect of compound system enhanced the intermolecular attraction between HPVA molecule and CTAB molecule, which lead to a tighter interfacial film to maintain a better stability of emulsions. For low permeability cores, displacement tests showed an additional oil recovery of 12.4% by the injection of spontaneous emulsification system. These remarkable performances enable this system an ideal candidate for oil recovery enhancement.

Novel Self-Nano-Emulsifying Drug Delivery Systems Containing Astaxanthin for Topical Skin Delivery

Astaxanthin (ASX) is a potent lipophilic antioxidant derived from the natural pigment that gives marine animals their distinctive red-orange colour and confers protection from ultraviolet radiation. Self nano-emulsifying drug delivery systems (SNEDDS) have been successfully developed and evaluated to increase the skin penetration of ASX and target its antioxidant and anti-inflammatory potential to the epidermis and dermis. SNEDDS were prepared using a low-temperature spontaneous emulsification method, and their physical characteristics, stability, antioxidant activity, and skin penetration were characterized. Terpenes (D-limonene, geraniol, and farnesol) were included in the SNEDDS formulations to evaluate their potential skin penetration enhancement. An HPLC assay was developed that allowed ASX recovery from skin tissues and quantification. All SNEDDS formulations had droplets in the 20 nm range, with low polydispersity. ASX stability over 28 days storage in light and dark conditions was improved and antioxidant activity was high. SNEDDS-L1 (no terpene) gave significantly increased ASX penetration to the stratum corneum (SC) and the epidermis-dermis-follicle region (E + D + F) compared to an ASX in oil solution and a commercial ASX facial serum product. The SNEDDS-containing D-limonene gave the highest ASX permeation enhancement, with 3.34- and 3.79-fold the amount in the SC and E + D + F, respectively, compared to a similar applied dose of ASX in oil. We concluded that SNEDDS provide an effective formulation strategy for enhanced skin penetration of a highly lipophilic molecule, and when applied to ASX, have the potential to provide topical formulations for UV protection, anti-aging, and inflammatory conditions of the skin.

Enhanced anti-psoriatic activity of tacrolimus loaded nanoemulsion gel via omega 3 - Fatty acid (EPA and DHA) rich oils-fish oil and linseed oil

Psoriasis is an autoimmune disease that affects around 3–4% of the population globally leading to skin inflammation. Tacrolimus is widely used in the treatment of psoriasis due to its ability to suppress inflammation and immune response. But formation of scaly plaques and dry patches are hurdle in delivering drug via topical route. The aim of present study was to develop, optimize and characterize tacrolimus loaded nanoemulsion gel to get enhanced anti-psoriatic activity. Nanoemulsion was prepared using spontaneous emulsification method combined with high pressure homogenization technique using fish oil and linseed oil (2 different oils), tween 80 (surfactant) and transcutol-P (co-surfactant). Fish oil and linseed oil were used as oil phase as they contain high amount of eicosapentaenoic acid and docosahexaenoic acid, and possess anti-inflammatory activity. The optimized nanoemulsions (fish oil an linseed oil containing nanoemulsions) attained using central composite rotable design had desired average hydrodynamic diameter (<130 nm) and narrow PDI along with high percentage transmittance (>95%). The optimized nanoemulsion was transformed into nanoemulsion gel using 1% carbopol-934. The cumulative drug permeated through the skin was 1.3 and 1.4-fold higher for nanoemulsion gel-F and L respectively compared to marketed ointment. The confocal laser scanning microscopy and dermatokinetic studies confirmed enhanced depth of permeation and skin retention (~1.5-folds) for developed nanoemulsion gel. In vivo study performed on mice using Imiquimod induced psoriasis-like inflammation model, showed significantly high anti-psoriatic activity in mice treated with nanoemulsion gels compared to marketed ointment. Significant reduction in the levels of cytokines (TNF-α and IL-6) in the skin, showed promising outcome in the treatment of psoriasis, of developed nanoemulsion gels compared to marketed ointment. Thus, it was concluded that fish oil and linseed oil integrated tacrolimus nanoemulsion gel could improve the efficacy of tacrolimus and is a promising carrier in the treatment of psoriasis.

Precise Control of the Surface and Internal Morphologies of Porous Particles Prepared Using a Spontaneous Emulsification Method.

Porous particles with controllable surface and internal morphologies were successfully prepared by a "one-step mechanical emulsification" technique via the control of spontaneous emulsification where self-emulsification is followed by mechanical emulsification. The morphological changes in the porous particles were determined not by the preparation conditions of the water-in-oil-in-water (w/o/w) emulsion but by the proportion of solvents that favors the stabilization of the spontaneously prepared water-in-oil (w/o) emulsion droplets acting as porogens. The proposed method for controlling the morphology of the porous particles could be applied to all particle-preparation systems based on emulsion-solvent evaporation using organic solvents. The methodology for the morphological control of porous particles independent of the concentration or composition of the polymer is considered valuable for future investigations into the aerodynamic performance and drug-release behavior of biomedical porous particles with complex shapes.

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and In Vitro Bioassay.

Purpose: The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug. Methods: The oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE). Results: F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model. Conclusion: The extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.

Nanoemulsions: Increasing possibilities in oral drug delivery

The objective of our work was to maximize the therapeutic efficacy of Atrovastatin by developing oil in water (o/w) nanoemulsion to increase its poor solubility and consequently enhance the oral bioavailability. The aim of investigation was to rectify the first-pass metabolism of Atorvastatin, using preparation of nanoemulsion as a prominent delivery system. Olive oil, surfactant (tween 80, tween 40, tween 20) and co-surfctants including polyethylene glycol was selected after solubility studies. Then pseudo-ternary phase diagram with surfactant/ cosurfactant ratio of 1:1, 2:1, 3:1 and 4:1 were constructed and spontaneous emulsification method. Titration method was used to optimize the Atorvastatin loaded nanoemulsions. The prepared nanoemulsion was characterized by globule size, refractive index, partition coefficient, viscosity, drug entrapment efficiency, in vitro drug release studies. Optimised nanoemulsion obtained was composed of olive oil (8.5 %w/w), tween 80 (11.5 %w/w) and water (80 %w/w). The results obtained showed an average globule size. The Optimized formulation showed an improvement in solubility of Atorvastatin. The use of pseudo-ternary phase diagram allows obtaining an optimal nanoemulsion with perfect stability for three months and a better solubilization capacity of Atorvastatin.

Development of a Spontaneous Emulsifying Technique Using Porous Microparticles with Water-soluble Polymers.

A novel spontaneous emulsification method using porous polymer particles was investigated for the facile preparation of emulsions without mechanical manipulation. Porous water-soluble polymer particles prepared by spray freeze-drying could absorb soybean oil via capillary action. When the particles were added to water, emulsification proceeded rapidly with the dissolution of the polymer. The importance of using a water-soluble polymer for particle formation for the formation of fine emulsions and maintenance of dispersibility was confirmed. This emulsification technology is expected to be applied to the development of formulations that improve the solubility and mucosal absorption of poorly water-soluble drugs.

Tocotrienols-rich naringenin nanoemulgel for the management of diabetic wound: Fabrication, characterization and comparative in vitro evaluations

The present research had been attempted to formulate and characterize tocotrienols-rich naringenin nanoemulgel for topical application in chronic wound conditions associated with diabetes. In due course, different phases of the nanoemulsion were chosen based on the solubility study, where combination of Capryol 90 and tocotrienols, Solutol HS15, and Transcutol P were selected as oil, surfactant, and cosurfactant, respectively. The nanoemulsions were formulated using the spontaneous emulsification method. Subsequently, Carbopols were incorporated to develop corresponding nanoemulgels of the optimized nanoemulsions. Thermodynamically stable optimized nanoemulgels were evaluated for their globule size, polydispersity index (PDI), surface charge, viscosity, mucoadhesive property, spreadability, in vitro release and release mechanism. Further, increasing polymer concentration in the nanoemulgels was reflected with the increased mucoadhesive property with corresponding decrease in the release rate of the drug. The optimized nanoemulgel (NG1) consisted of uniform dispersion (PDI, 0.452 ​± ​0.03) of the nanometric globules (145.58 ​± ​12.5) of the dispersed phase, and negative surface charge (−21.1 ​± ​3.32 ​mV) with viscosity 297,600 ​cP and good spreadability. In vitro release of naringenin in phosphate buffer saline revealed a sustained release profile up to a maximum of 74.62 ​± ​4.54% from the formulated nanoemulgel (NG1) within the time-frame of 24 ​h. Alternatively, the release from the nanoemulsion was much higher (89.17 ​± ​2.87%), which might be due to lack of polymer coating on the dispersed oil droplets. Moreover, the in vitro release kinetics from the nanoemulgel followed the first-order release and Higuchi model with non-Fickian diffusion. Therefore, encouraging results in this research is evident in bringing a promising future in wound management, particularly associated with diabetes complications.

Formulation of anti-larval nanoemulsion: Impact of droplet size on larvicidal activity against malaria vectors in Chhattisgarh, India

Mentha piperita (peppermint) essential oil nanoemulsion was prepared by low energy spontaneous emulsification method. GC-MS analysis revealed the composition of peppermint essential oil and menthol (45.2%) was the major bioactive compound along with menthone (15.39%), neomethol (8.1%), menthyl acetate (7.7%) and isomenthone (7.4%). Optimization of the nanoemulsion preparation process was done by Response Surface Methodology (RSM) with Central Composite Design (CCD). The droplet diameter and polydispersity index at optimized conditions (15% oil concentration, 25% surfactant concentration and Tween80 as surfactant) were 39.2 nm and 0.22 respectively. Optimized peppermint oil nanoemulsion (OPNE) was optically transparent, spherical in morphology and was stable for 6 months. OPNE formulation demonstrated dose, time and size-dependent larvicidal activity against malaria vectors with LC50 value of 48 ppm and 123 ppm against Anopheles culicifacies and Anopheles stephensi respectively. The LC50 values were 90 ppm and 163 ppm against Anopheles culicifacies and Anopheles stephensi correspondingly for the bigger droplet size formulation (PNE, droplet diameter: 129.6 nm) confirming the droplet size-dependent larvicidal activity of the nanoemulsion. The results of this study propose that peppermint oil-based nanoemulsion possibly be used as an eco-friendly larvicide for mosquito vector control strategies.

Optimization of Surfactant- and Cosurfactant-Aided Pine Oil Nanoemulsions by Isothermal Low-Energy Methods for Anticholinesterase Activity.

Highly stable pine oil-loaded nanoemulsions were evaluated for nutraceutical and storage stability applications. Pine oil-loaded nanoemulsion preparation was done with pine oil as the oily phase and additionally with different ratios of the non-ionic surfactant (Tween 80) and cosurfactant (ethanol) in an aqueous solution using the isothermal low-energy or spontaneous emulsification method. A transparent and stable nanoemulsion was obtained with a combination of pine oil (5 wt %), surfactant mixture (35 wt %), and water quantity sufficient (qs) by the isothermal low-energy method. The mean droplet size and ζ-potential of the fabricated nanoemulsion were ≈14 nm and −3.4 mV, respectively. The size of the transparent nanoemulsion increased to ∼45 nm and showed turbidity at 60 °C. Microrheological investigation highlighted the gel–sol–gel conversion in the presence of applied angular frequency at 25 °C. The loss modulus shifted to lower frequency at 60 °C in comparison to other temperatures. The anticholinesterase (AChE) inhibition activity of the pine oil-loaded nanoemulsion suggested a possible therapeutic value, and at 0.10% concentration of the nanoemulsion, the AChE inhibition activity was ≈95.72 ± 5.59%. These studies have important implications in fabrication and optimization of a nanoemulsion as a delivery system for combating reminiscence in Alzheimer’s disease and application in the nutraceutical-based industry. This isothermal low-energy method offers an advantage of preparing an edible oil delivery system using simple and rapid operational parameters.

&lt;p&gt;Chlorhexidine Nanoemulsion: A New Antiseptic Formulation&lt;/p&gt;

IntroductionNanoparticle solutions have been studied to improve antimicrobial effect. The aim of this study was to develop, characterize, and evaluate the in vitro and in vivo antiseptic efficacy of 0.25% aqueous-based chlorhexidine nanoemulsion (NM-Cl 0.25% w/v).MethodsThe NM-Cl 0.25% w/v (2.5mg/mL) and free chlorhexidine nanoemulsion (FCN; same composition of NM-Cl without the molecule of chlorhexidine) were synthetized by the spontaneous emulsification method. Characterization analyses of physical and chemical properties were performed. The NM-Cl 0.25% w/v was compared with chlorhexidine 0.5% alcohol base (CS-Cl 0.5%) in vitro studies (microdilution study and kill curve study), and in vivo study (antisepsis of rats dorsum). Kruskal–Wallis test was used between groups and inside the same group, at different sample times and the Mann–Whitney test was performed when difference was detected.ResultsThe NM-Cl 0.25% w/v presented adequate physicochemical characteristics for a nanoemulsion, revealing a more basic pH than FCN and difference between zeta potential of NM-Cl 0.25% w/v and FCN. The NM-Cl 0.25% w/v and CS-Cl 0.5% solutions were more effective on Gram-positive than on Gram-negative bacteria (p≤0.05). NM-Cl 0.25% w/v presented upper antiseptic effect in the microdilution study and residual antiseptic effect was maintained for a longer time when compared to CS-Cl 0.5% (kill curve study). The four-fold (minimal inhibitory concentration) of NM-Cl 0.25% were the formulations with most durable effect within those tested, presenting residual effect until T6 for both bacteria. In the in vivo study, both formulations (NM-Cl 0.25% w/v and CS-Cl 0.5%) had a reduction of the microorganisms in the skin of the rats (p<0.0001) not revealing any difference between the formulations at different times, showing the antiseptic effect of NM-Cl (p≤0.05).ConclusionBoth in vitro and in vivo experiments demonstrated that NM-Cl showed promising future as an antiseptic for cutaneous microbiota.

Thermosensitive Brinzolamide in situ Gel Nanoemulsions, in vitro and ex vivo Evaluation

Brinzolamide (BZ) is a carbonic anhydrase inhibitor with selectivity and affinity for the carbonic anhydrase type II isoenzyme that administrated topically as an ophthalmic suspension for reducing intraocular pressure. In this study, BZ in situ gel nanoemulsions (NEs) were developed and evaluated for transcorneal permeation via the bovine corneal membrane. The spontaneous emulsification method was employed to prepare BZ in situ gel NEs. Various physicochemical characteristics, including particle size, polydispersity index, pH, refractive index, and viscosity, were evaluated. Accelerated physical stability and in vitro drug release, as well as transcorneal permeation studies was performed by applying the Franz-type diffusion cells. Thermosensitive BZ in situ gel NEs with desired physicochemical features and sustained release profiles were designed in the current study. Optimized Formulations exhibited physical stability under different conditions. The transcorneal permeation of formulations was higher than that of suspension, especially for F3b formulation. According to the present in vitro and ex vivo evaluations, it is concluded that in situ gel NEs could be a topical administration of BZ as a suitable ocular drug delivery system.

Redox-Driven Spontaneous Double Emulsion.

The formation of spontaneous double emulsions is a peculiar phenomenon in emulsion systems. When compared to the traditional one-step and two-step methods for preparing double emulsions, spontaneous emulsification can not only steadily load uniform water droplets into an oil phase, but can also facilitate the preparation of emulsions with higher stability. However, the limited solubility of salts, which are typically used to modify osmotic pressure, in organic oils has inhibited the viability of this method for the preparation of W/O/W double emulsions. In this paper, a redox-driven spontaneous emulsification method is developed and investigated. Instead of employing oil-soluble salts, an oxidation reaction is implemented in the oil phase, which produces cation radicals and iodide counterions to generate osmotic pressure. Additionally, amphiphilic polymer chains are harnessed as stabilizers for the newly formed W/O interfaces. Various characterization methods have been used to elucidate the mechanism of both the oxidation reaction and the spontaneous formation of double emulsions.