Application of Novel Nanoemulsion in Drug Targeting


Akkas Ali Ahmed*, Dr. Suvakanta Dash1

1,*Department of Pharmaceutics, Girijanadha Chowdhury Institute of Pharmaceutical Science, PIN- 781017 PO- Azara Dist- Kamrup  state- Assam, India 

*Corresponding Author E-mail:



Nanoemulsions are usually having micron sized emulsions which acts in the drug carriers for improvement of the drug delivery for therapeutic agents in the different applications. They have been shown great promises for upcoming the generation of cosmetic, diagnosis, drug therapeutics and biotechnologies. The nanoemulsions are advantages over conventional emulsion due to their very small particle size which confers them the stability against sedimentation and creaming. The major application for nanoemulsions is the formulation of nanoparticles by using polymerizable monomer as disperse phase there nanoemulsion particles act as a nanoreactors. In this context the present review highlighted briefly the different methods of preparation of nanoemulsion, characterization and its application in drug targeting and delivery.


KEYWORDS: Nanoemulsion, optimization technique, methods of nanoemulsion formulation, Application of Nanoemulsion.





Nanoemulsion is a heterogeneous system and it consists of two immiscible phase, one phase is oil phase while other is aqueous phase, the droplet is submicron size range of 20-200 nm. It is thermodynamically stable which can be determined by freeze-thaw cycle. It is optically clear, transparent formulation of nanoemulsion1. Now-a-day’s nanoemulsions are frequently and widely  used for various purpose like delivery of vaccine, DNA encoded drug antibiotics, cosmetic and topical preparations and can be administrated via various routes like oral administration, pulmonary, ocular transdermal, Intranasal etc, biodegradable polymeric nanoparticles used as drug delivery systems2,3. Nanoemulsion, which is categorized as multiphase colloidal dispersion is generally characterized by its stability and clarity.


The dispersed phase typically comprises small particles or droplets and has very low oil/water interfacial tension. Nanoemulsion is formed readily and sometimes spontaneously, generally without high-energy input. In many cases a cosurfactant or cosolvent is used in addition to the surfactant, the oil phase and the water phase. o/w emulsions are mostly useful as water washable drug bases and for general cosmetic purposes, while w/o emulsions are employed more widely for the treatment of dry skin for motorization and emollient applications. Gels for dermatological use have several favourable properties such as being thixotropic, greaseless, easily spreadable through, easily removable or non-greasy, emollient, non-staining, compatible with several excipients and water-soluble or miscible. Emulgels are emulsions, either of the oil-in-water or water-in-oil type, which are gelled by mixing with a gelling agent. They have a high patient acceptability since they possess the previously mentioned advantages of both emulsions and gels. Therefore, they have been recently used as vehicles; Nanoemulsions are formulated using oil such as glyceryltricaorylatecaprate, surfactants/ cosurfactants and aqueous phase. Surfactants such as tween 80, PEG (>4000), poloxamer, Brij-35 etc are used3 Surfactants added in formulation approved are 'Generally Recognized as Safe' (GRAS) by the FDA.


Types of Nanoemulsion:

Nanoemulsion are classified into mainly three types on the basis of their composition

1.        Oil in water Nanoemulsions; in oil in water nanoemulsion oil dispersed in water. Hence dispersion medium is water and this kind of noemulsion can be found in application which has small quantity of fatty material like moisturizing, creams. Example: milk which is also o/w types of emusion.

2.        Water in oil Nanoemulsions; In case of the Water in Oil Nanoemulsion water droplets are found to be dispersed in continuous oil phase.

3.        Bi-continuous Nanoemulsions In case of bi- continuous nanoemulsion oil and water are interdispersed within the system.


Advantages of Nanoemulsion:

1.        Nanoemulsions are thermodynamically and kinetically stable therefore flocculation aggregation Creaming and coalescence do not occurs within the system.

2.        It is nontoxic and non irritants.

3.        Nanoemulsion is administered by various routes, like as oral, topical, parentral and transdermal and intranasal administration.

4.        Nanoemulsions can deliver both hydrophilic and lipophilic systemic drugs.

5.        Droplet size are nano in the range of 20-200 µ, so surface area is higher thus increases the rate of absorption  and reduces variability, thus enhances bioavailability of drug.

6.        Nanoemulsions are suitable for human and veterinary uses because they do not Damage human or animal cell.

7.        It protects the drug from hydrolysis and oxidation due to encapsulation in oil-droplet. It also provides taste masking.

8.        Nanoemulsion also enhances skin permeation of drug through skin and shows good absorption of drug4


Disadvantages of Nanoemulsion:

1.     Large concentration of surfactants /cosurfactants is required for stabilization of the formulation.

2.     Its stability is affected by temperature and pH.

3.     Instability can be caused due to Oswald ripening effect5


Ideal properties of Nanoemulsion:

1.        It should consist of uniform dispersion of fine and nano sized droplets of internal phase, which should not aggregate and if they do, must not coalesce to form large droplet.

2.        The internal Droplets should not cream up or down and if they do the cream layer should be re dispersible without phase inversion it should be remain in the original type.

3.        It should not be regarded by microbes on storage

4.        It should not be stable in various temperature

5.        It should not be rancid or degradation due to the oxidation6. Example. Oil and fats


Methods of preparation of Nanoemulsion:


In the formulation of nanoemulsion, nanoemulsion is subjected to use the ultrasonic, which is high frequency sound produced to reduction of the particle size. Emulsion is formulated to fix composition of the emulsion and then it was agitated at ultrasonic frequency of (20 kHz of layer) causing the droplet to break into nano size droplets. The emulsion is recirulated through region of high shear to produce uniform droplet size distribution. In this method the water jacket is used to control and maintain the temperature and the ultrasonic frequency reduces the particle size (fine droplet) 7


High-Pressure Homogenization:

This method is performed by applying a high pressure over the system having oil phase, aqueous phase and surfactant or co-surfactant. The pressure is applied with the help of homogenizer. Some problems associated with homogenizer are poor productivity, component deterioration due to generation of much heat. With this method only Oil in water (O/W) liquid nanoemulsion of less than 20% oil phase can be prepared and cream nanoemulsion of high viscosity or hardness with a mean droplet diameter lower than 200 nm cannot be prepared8. The flow chart for processes of homogenization is discussed in fig.1


Effect of Homogenization Pressure:

It is optimized the process parameter ranging from 100 to 150 bars. The higher is the size the lower is the particle size obtained e.g., RMRP 22.


No. of Homogenization cycles:

The higher the homogenization cycles the smaller is the particle size obtained. The cycles are carried out in 3, 4 or 10 cycles. The number of cycles is analyzed by polydispersity index of drug after each cycle.


Fig 1: High pressure homogenization



Microfluidization technology makes use of a device called ‘MICRO FLUIDIZER”. This device is as shown in the figure 2, creates a high pressure positive displacement pump (500-200 psi).Microfludizer forces the product within the interaction chamber, consisting of a small channels called micro channels. The product flows through the micro channels on to an impingement area resulting in very fine particles of submicron range. Both the solution are combined together (aqueous phase and oily phase) and processed in an inline homogenizer to yield a course emulsion. The course emulsion is into a micro fluidizer where it is further processed to obtain a stable nanoemulsion9


Fig 2: Processes of microfluidization by microfluidizer.


Phase inversion method:

It is done for nanoemulsion generally prepared by phase inversion method and self emulsification method to measures the dispensability of nanoemulsion.


Spontaneous Emulsification:

Spontaneous emulsification may occur when immiscible liquids remained in non-equilibrium conditions. This phenomenon is enhanced by gradients of chemical potentiality between the phases, which under certain conditions leads to negative values of free energy of emulsification. This phenomenon of spontaneous emulsification, also known as self emulsification methods.


It involves three main steps:

·         Preparation of homogeneous organic solution composed of oil and lipophilic surfactant in water miscible solvent and hydrophilic surfactant.

·         The organic phase was injected in the aqueous phase under magnetic stir-ring giving o/w emulsion.

·         The water-miscible solvent was re-moved by evaporation under reduced pressure10


Solvent Evaporation Technique:

Solvent evaporation Technique involves preparing a solution of drug followed by its emulsification in another liquid that is non-solvent for the drug. Evaporation of the solvent leads to precipitation of the drug. Crystal growth and particle aggregation can be controlled by creating high shear force-using high-speed stirrer11


Hydrogel Method:

Hydrogel method is quite same as solvent evaporation method. Difference between this two methods is that the drug solvent is miscible with drug anti-solvent. Higher the shear force prevent crystal growth and Ostwald ripening12


Characterization of Nanoemulsion:

Thermodynamic Stability:

Thermodynamic Stability Studies: Nanoemulsion was introduced  to various storage conditions of temperature and humidity to determined  their stability as mentioned in the  ICH guidelines Q1A (R2) chemical and physical stability of nanoemulsion were being evaluated for six months by storage condition at 30 ± 20C / 65 ± 5% RH and 40 ± 20C / 75 ± 5% RH. Thermodynamic stability tests were performed to determined the metastability of the formulation. Apart from this formulations are centrifuges for 30 minute at 3500 rpm. The formulations which does not show any phase separations take for the heating and cooling cycle. Six cycles required between refrigerator temperatures of 4ºC and 45ºC for a duration of 48 hours. If the formulations stables at this mentioned temperatures are subjected to further studies for the freeze-thaw cycle test. Three freeze-thaw cycles is done for the formulations between –21ºC and +25ºC. Those formulations that survive thermodynamic stability tests are select for the further studies of optimization13


Dynamic Light Scattering Spectrophotometer:

Dynamic Light Scattering Spectrophotometer is a technique in physical science that is used to determine the size distribution profile of small particles in suspension emulsion or polymers in solution. DLS is also used to characterize size of various particles size including proteins in formulation, polymers for formulation, micelles, carbohydrates, and nanoparticles. If the system is not disperse in to the size, the mean effective diameter of the particles is determined. This measurement depends on the size of the particle surface structure core size and particle concentration, apart from this the type of ions in the medium. Dynamic light scattering measurements are done at 90° using a neon laser of wavelength 632nm. The particle size and particle size distribution is determined by dynamic light scattering spectrophotometer as mentioned earlier14


Zeta Potential:

The most cases, colloidal particles possess a positive or negative electrostatic charges are used. As electrical fields are applied to the particle dispersion for formulation, the particles are start migrating in oppositely charged directions within the system. As particles are irradiated in migration, scattering light causes Doppler shift depending upon electrophoresis mobility. NanoPlus software are usually used to calculates the amount of Doppler shift followed by electrophoretic mobility and zeta potential by combining a heterodyne system and photon correlation method to perform Fourier transform (FFT) Slipping level Major part of medium of obtained correlation function. Zeta potential can be determined or measures the surface charge of the nanoemulsion by the help of a mini electrode.15 Processes of zeta potential is shown in figure 3.


Fig3: Processes of zeta potential


Transmission Electron Microscopy (TEM):

Transmission Electron Microscopy is a microscopically technique in which a beam of electrons is passes through an ultra-thin specimen, interacting with the specimen as it passes through it. An image is created from the interaction of the electrons transmitted through the specimen; the followed image is magnified and  focused  onto an imaging device, such as a  fluorescent screen, on a layer of photographic film, or to be detected by a sensor such as a charge-coupled device.TEM is a very much simple method to determine the size, number, weight and the size, weight and its stain with uranyl acetate and placed over the grid which is coated with monolayer polymer, after that water is evaporated and observation is done by TEM16.The images of TEM is shown in the fig.4





Fig4: (A) Process, (B) Image of of TEMP


Drug Content:

Certain amounts of nanoemulsion was taken and dissolved using 100ml of distilled water and sonicated for the period of 15 minute than filtered the above solution by whatman filter paper due to the presence of carbopol gel. Further dilutions were made by using water prepared concentration within Beer’s range. The absorbance was taken by UV-Visible spectrophotometer and drug content was calculated by using Y= mx+c equation. Apart from this Western Blot method also is used to measured amount of drug present in the formulation 17


Viscosity Measurement:

Viscosity of nanoemulsion can be measured by applying the rotary viscometer at different rate and temperature and speed. Nanoemulsions is having very low viscosity.18 Brookfield viscosity usually refers to a viscosity measurement carried out by a Brookfield Viscometer in laboratory skills. There are several models available for viscometer from Brookfield but the mostly all of them operate in the same manner: the viscometer motor rotates the spindle at different speed (measured in rpm) or shears rate and the viscometer calculate the resistance of rotation and reports a viscosity value.  Various spindle are designed, depending on the nature of the sample and the spindle are used.


Application of Nanoemulsion:

In modern science the nanoemulsion are applied in drug targeting, biotechnologies, diagnosis and other drug delivery system as shown in figure 5.


Prophylactic agent to fight against bioterrorismattack19

The nanoemulsion formulations cane be formulated based on containing antimicrobial agents which is having prophylactic activity to fight against the bioterrorism attack. Use of nanoemulsions as a prophylactic medicated dosage form, a human protective treatment which prevent the people exposed to bioterrorism such as organism as Anthrax and Ebola. The broad-spectrum nanoemulsions we rechecked over surfaces by the United State Army (RestOps) in the month of Dec. 1999 for decontamination of Anthrax spore. It was checked again by RestOps in March 2001 as a chemical decontamination agent by the same U.S Army. This technology has been tested on gangrene and clostridium botulism spores, and can even be used on contaminated wounds to salvage limbs. The nanoemulsions can be formulated into a creams, foam, liquid and spray to decontaminate a large number of materials during the boi-war in different country.


In cosmetic formulations:

In case of cosmetic formulation the problems observed are mainly poor absorption or permeation of drugs through different skin layers, by the help of nanotechnology and nanoemulsion, these problems can be overcome by increasing the absorption and permeation of cosmetic in skin which can be triggered by using smaller particle size. Recently the importance of nanoemulsions as a vehicle for the controlled delivery of drugs in cosmetics has been increasing which is in fact an optimized dispersion of active ingredient. Due to their presence of lipophilic character, nanoemulsions are more suitable for the passes of lipophilic drug than liposomes. Nanoemulsions support the skin permeation of active constituents and results to increase concentration in the skin layers. One more advantage is the small-sized droplet with its higher surface area permit effective delivery of the active to the skin. More ever, nanoemulsions gain increasing interest due to their own bioactivity effects. This may decreases the trans-epidermal water loss (TEWL), insist that the barrier function of the skin is strengthened. Nanoemulsions are acceptable in cosmetics because of there are no chance of creaming, sedimentation, flocculation or coalescence of formulation, which is observed within microemulsions. The incorporation of potentially irritating surfactants can be avoided by using high-energy equipment during manufacturing process without PEG nanoemulsions for cosmetics has been also developed and formulations exhibited good stability of formulations19


Fig 5: Different application of nanoemulsio.


Antimicrobial preparation:

Antimicrobial drugs can be prepared as nanoemulsion which is oil in water nanoemulsion formulation, droplets range within 600nm which is stabilized by surfactants and alcoholic. The antimicrobial nanoemulsions having a broad spectrum activity for bacteria which is like E. coli, salmonella, S. aureus; enveloped the viruses as like HIV,  and herpes simplex, fungi as like Candida, Dermatophytes, and as like Anthrax. Nanoemulsions particles are thermodynamically drive as in fuse with the lipid-containing organisms. This fusion is increased by the electrostatic affinity within the cationic charges of the nanoemulsionas well as the emulsion formulation and negative ion over the pathogen. When enough nanoparticles fused with the pathogens, they release part of the energy framed within the emulsion or nanoemulsion. Both of the active constituents and the energy destabilized the pathogenic lipids membrane, which is resulting in the cell lysis and   to the death of organism. In case of spores, additionaly are germination enhancers mixed into the emulsion formulation. Once starting of germination takes place, the germinating spores become susceptible to the antimicrobial action of the nanoemulsions. An aspect of the nanoemulsions is their highly selective toxicity to microbes at concentration range that are forming none irritating to skin and mucous membrane. Safety range of nanoemulsions is because of the low amount of detergent in each droplet, yet when acting in concert, these droplets have enough energy and surfactant to destabilize targeted microbes without affecting healthy cells. Nanoemulsions can get a level of topical antimicrobial activity, that can only be previously achieved by systemic antibiotics20


Vaccines delivery:

The nanoemulsion are used as effective vaccine delivery system to deliver in attenuated viruses. This medication delivery system uses nanotechnology to vaccinate against human Immune-deficiency virus (HIV). There are recent evidence that HIV is infect in the mucosal immune system. Therefore, the developing of mucosal immunity by the use of nanoemulsions is becoming very important in the further fight with HIV. The oil-based emulsion is administrated. Nanoemulsions advances in Formulation, Characterization, and applications in Drug Delivery administrated in to the nasal route too as opposed to traditionally used vaccine. Recent trands and researches results indicate that genital mucosa immunity may be attained with vaccines that are administered to the nasal mucosa route. Nanoemulsions are being used to transport inactivated organisms to a mucosal surface to produce an immune response. The first applications as a vaccine, influenza vaccine, and an HIV vaccine is proceed to clinical trials for future studies. The nanoemulsion causes proteins applied to the mucosal surface to be adjuvant and it helps uptake by antigen presenting cells. This results in the significant systemic and mucosal immune response due to that the production of specific IgG and IgA antibody as well as the cellular immunity. Work in influenza has shown that animals can be prevented against influenza after a single mucosal exposure to the virus mixed with the nanoemulsions. Research has also shown that animals exposed to recombinant gp120 in nanoemulsions on their nasal mucosa create significant responses to HIV, thus giving a basis to use this material as an HIV vaccine. Additional research has been ongoing to complete the proof of concept in animal trials for other vaccines including Anthrax and Hepatitis- B20


Oral delivery of poorly soluble drugs:

Nanoemulsions formulation are usually used to increasing in oral bioavailability of hydrophobic drugs. Paclitaxel which is selected for model of hydrophobic drug. The o/w nanoemulsions were made by pine nut oil as a emulsifying agents which is the internal oil phase of nanoemulsion and water as a external phase and egg lecithin is primarily used emulsifier. Stearylamine and deoxycholic acid were being using to give positive and negatively charge to the emulsions formulation, respectively. The formulated nanoemulsions had a particle size range of around 100-to 120 nm and zeta potential ranging from 34 mV- 245 mV. In case of oral administration of nanoemulsions, a significantly high in concentration for paclitaxel was observed in the systemic circulation of human body which comparing to control aqueous solution. The resulting of this study insist that nanoemulsions are promising in novel formulations which can increased the oral bioavailability for the hydrophobic drugs21.


Parenteral drug delivery:

Parenteral drug delivery is most and commonly used route of administration which is effective in a drug administration usually adopted for actives with low bioavailability and narrow therapeutic index formulation. Their capability to dissolve the huge quantities of hydrophobic with their mutual compatibility and ability to protect the drugs from hydrolysis and enzymatic degradation make nanoemulsions ideal vehicles for the purpose of parenteral transport. Further, the frequency and the amount of dosage for injections can be reduced throughout the drug therapy period as these emulsions are shows the great release of drugs in a sustained and controlled system over long periods of time. Additionally, due to the lack of flocculation, sedimentation, and creaming, of formulation which combined with the large surface area and free energy, offer certainly advantages over emulsions of larger particle size forms, for this route of administration. They are very large interfacial area positively influences over the drug transport and their delivery, along with targeting them to specific sites. Major clinical and pre-clinical trials have been carried out with the parenteral nanoemulsion-based carriers. Advances in these novel drug delivery systems have been reviewed by Patel and Patel. Nanoemulsions loaded with thalidomide have been synthesized where a dose as low as 25 mg leads to plasma concentrations which can be therapeutic. However, a significant decrease in the drug content of the nanoemulsion was observed at 0.01% drug formulation after two months storage of the formulation which could be overcome by the addition of polysorbate 80. Chlorambucil, a lipophilic anticancer agent that has been used for breast and ovarian cancer targeted drug delivery. Its pharmacokinetics and anticancer activity have been studied by loading it in parenteral emulsions prepared by using as high energy ultrasonication method, by applying high frequency sound in the system. Treatment for colon adenocarcinoma in the mouse with this nanoemulsion which leads to higher tumor suppression rate compared to the plain drug solution treatment, thats concluding the drug loaded emulsion could be an effective carrier for its delivery in cancer targeted. Carbamazepine is widely used anticonvulsant drug that has no parenteral treatment available for patients because of its poorly water solubility. Kelmann et al. have developed a nanoemulsion for its intravenous delivery of drug, which shows favourable in vitro drug release kinetics. Parenteral administered nanoemulsion formulations of the following drugs have been documented as well as diazepam, propofol, dexamethasone, etomidate, flurbiprofen and prostaglandin E1. The high lipophilicity of diazepam (an anxiolytic and (sedative) makes the use of solvents (such as propylene glycol phenyl carbinol and ethanol) for the dissolution of the drug in the case of  aqueous preparations (Valium® and Stesolid®) which is necessary for pain and thrombophlebitison the patient during the administration as injection. The development of a nanoemulsion, marketed under the name of Diazemuls® (Kabi- Pharmacia) allows for the dicreases of these side effects, keep in stages of distribution and elimination similar to Valium®. However, higher amount of doses for Diazemuls® are necessary to obtain the same effect as Valium® since this leads to a higher free fraction of plasma diazepam. The solution for intravenous administration of etomidate (hypnotic short) because of stability problems, its composition contains 35% of propylene glycol (Hypnomidate®). Due to the presence of high osmolarity of the solvent, the administration is shown various adverse effects like hemolysis, thrombosis, thrombophlebitis, and pain at the site of administration. A nanoemulsion loaded with 2 mg/ml Lipofundin® etomidate in medium triglyceride named as Lipuroetomidate ® (B. Braun) have been developed. The emulsion allowed the decreased of the hemolytic and venous sequelae, apart from the pain at the time of administration as injection. The pharmacokinetics and pharmacodynamics of propofol (anesthetic) is complex. It has an initially quick distribution for the periods of 2-3 minutes, with high variability between patients and reduced concentrations to sub-therapeutic levels within minutes. However, because of its high lipophilicity, it has a large volume of distribution and its complete the elimination from the body can take days. Due to the presence of anaphylactic effects which associate with the Cremophor EL, present in the original formulation of propofol nanoemulsion acts as a vehicle for this drug containing composition in soybean oil as emulsifying agents besides this glycerol, egg yolk lecithin and disodium edentate, this vehicle also helped to decreased the volume of distribution of the drug, accelerating their processes of clearance by the responsible agencies. This formulation also allowed the use of minimal effective dose need to produce the needed therapeutic activity, allowing a rapid onset and recovery from anesthesia, while compared to a nonlipid (ethanol) solution, thereby generating greater security administration, due to the lower continuous accumulation of the drug, and eliminating the need for constant adjustment of the dose. This product was approved in 1989 in the United States, under the name of Diprivan® 1 or 2% (AstraZeneca / APP Pharmaceuticals). In Brazil, the product is available as Lipuro 1% (B. Braun) and Diprivan® 1 and 2% (AstraZeneca), besides the generic 1% (Eurofarma Labs). The various generic composition are currently available by an additional factor of variability in response between individuals in the induction of anesthesia, besides the pharmacokinetic characteristics of the drug itself and the differences in lipoprotein profile of each patient, because of the high binding of propofol to low density lipoprotein and albumin. Because of the related pain due to the injection site and increased triglyceride levels after administration for long periods of time, some changes in the formulation of Diprivan® adverse effects have been revealed, including some already being marketed as Propofol® Lipuro (B. Braun) as oil core which contains a mixture of oils. Due to the addition of more number of oil to the formulation allowed the decrease of pain on injection because to increased incorporation of the drug in the oily core and the lower amount of free propofol phase the external aqueous emulsion. Alternative formulations is being developed, for example, the incorporation of high concentrations of propofol (6%) in the nanoemulsion, or the development of a propofol prodrug in the solution (Aquavan®).Furthermore, shows the excellent anti-inflammatory activity of the dexamethasone, the clinically use of corticosteroids are found as the large numerous side effects. To circumvent these drawbacks, lipophilic prodrugs in the body that are gradually hydrolyzed to the active metabolite can be used (thus presenting prolonged anti-inflammatory effect). The advantage is the use of lower doses than those used in conventional water soluble form (dexamethasone phosphate), decreasing the risks of adverse effects. Considering that nanoemulsions are picking up by inflammatory cells of the mononuclear phagocytic system, nanoemulsions are used as a vehicle for the lipophilic prodrug for dexamethasone (palmitate), which is available in market as Limethason® (Green Cross Co. /Mitsubishi Tanabe Pharma Co.). Limethason® showed great results for the treatment of rheumatoid arthritis, as well as West syndrome, inflammatory diseases, and other autoimmune diseases. While the solution of dexamethasone phosphates quickly distributed in water-rich tissues like as muscles, the nanoemulsion is accumulated mainly in tissues inflamed organs such as liver and spleen. The bio distribution profile is different even if the elimination pattern is similar between the two. Limethason® removed over 80% of the phagocytic activity of macrophages at a concentration for 0.03 mg/mL. Flurbiprofen (non-steroidal anti-inflammatory oral use), a lipophilic drug, is used to treat rheumatoid arthritis and other inflammatory diseases which associated or not with cancer. Thenon-availability of oral and/or various gastrointestinal effects caused by this drug often required the use of the parenteral route. Considering the more local irritation caused by the sodium salt of flurbiprofen, it was developed as a prodrug of flurbiprofen (cefuroxime) due to the lipophilicity of the latter especially in soybean oil, it was incorporated in nanoemulsions for parenteraly used dosage form (Ropion®, Kaken Pharmaceuticals Co.,Lipfen®, Green Cross Co.), and is has been marketing in the Japanese since 1992. Administration of Ropion® resulted in an increase in area under the concentration-time curve and reduced clearance when compared to the solution. The incorporation of the drug into nanoemulsions containing unsterilized ethyloleate, lecithin and modified egg yolk led to a less drug accumulation in organs such as the liver and spleen because of the lower uptake by the mononuclear phagocyte system. Prostaglandin E1, which is synthesized in several places of the body, is responsible for various physiological effects like as vasodilatation, lowering of blood pressure, angiogenesis, and prohibits the formation of platelet aggregation. When administered for treatment of various diseases, it having a short half-life, so high doses are needed which leads to numerous adverse effects like hypotension, diarrhea, local irritation, and pain. In this context, nanoemulsions were marketed in 1975, PGE1 is complexed to cyclodextrins, in 1985, prostaglandin E1 incorporated in lipid nanoemulsions formulation (Liple®, Mitsubishi Tanabe Pharma Corporation, Palux®, Taisho Pharmaceutical) Lipid formulations are used for the treatments of cardiovascular diseases because they accumulate in the walls of injured vessels, passes the drug to the site of vascular injury and to protects from rapid inactivation by the lungs22


Pulmonary drug delivery:

The lung is an affinitive targeted drug delivery because of non-invasive administration through inhalation aerosols, avoidance of first-pass metabolism, direct delivery to the site of action in case of the treatment of respiratory diseases, and availability of a huge surface area for local drug action and systemic absorption of drug. Colloidal carriers (i.e., nanocarrier systems) in pulmonary drug delivery having many advantages like the potential to achieve relatively uniform distribution of drug dose among to the alveoli, achievement of enhanced the solubility of the drug from its own aqueous solubility, a sustained drug release which consequently decreased dosing frequency, increased patient compliance, reduced the incidence of side effects, and the potential of drug internalization by cells. Until now, the submicron emulsion system has been not yet fully exploited for pulmonary drug delivery and very less has been published in this area. Bivas-Benita et al. reported that cationic submicron emulsions are promising carriers for deoxyribonucleic acid vaccines to the lung since they are able to transfect pulmonary epithelial cells, which possibly induce cross-priming of antigen-presenting cells and directly activate dendritic cells, resulting in stimulation of antigen-specific T-cells. Therefore, nebulization for submicron emulsions could be a future research area. However, extensive studies are required for the successful formulation of inhalable submicron emulsions because of the possible side effects of surfactants and oils on lung alveoli function (adverse interactions with lung surfactant). A novel aerosol system has been used widely for the pulmonary delivery by using different devices, salbutamol using lecithin-stabilized microemulsions formulated in trichlorotrifluoroethane23


Gene delivery vector:

Emulsion systems have been come forwarded as alternative transfer of gene vectors to liposomes. Studies for other emulsion in gene delivery (non-pulmonary route) have shown that binding of the emulsion/DNA complex has found more stronger than liposomal carriers. Nanoemulsion’s advances in Formulation, Characterization and different applications in Drug Delivery system, delivered genes much more efficiently than liposomes. Silva et al evaluated factors that influence DNA compaction in cationic lipid nanoemulsions [cationic nanoemulsions containing stearylamine (a cationic lipid that presents a primary amine group when in solution, which is able to compact genetic material by the electrostatic interactions, and in dispersed systems such as nanoemulsions this lipid usually do anchors on the oil/water interface conferring a positive charge. Stearylamine influence incorporated the phase (water or oil), at the time of complexation, andincubation temperature was studied. The complexation rate was assessed by the electrophoresis immigration on agarose gel 0.7%, and nanoemulsion and lipoplex characterization was carried out by using dynamic light scattering (DLS) as a characterization of nanoemulsion. The results was demonstrated that the best DNA compaction process happened 120 minute after the complaxation forms, at very low temperature (4 ±1 °C), and after cationic lipid incorporation into the aqueous phase. Although the zeta potential of lipoplexes was lower than the results found for basic nanoemulsions, the granulometry of formulation did not change. Moreover, it was demonstrated that lipoplexes were suitable vehicles for gene delivery24,.25,26,


Non-Toxic Disinfectant Cleaner:

A nanoemulsion are nowadays commercially available and using as disinfectant cleaner that included the healthcare, hospitality, travelling, food processing, and military applications has been developed by the EnviroSystems, Inc. That inhibits or killed the diseases like tuberculosis and a wide spectrum of viruses, fungi and bacteria in 5-10 min with none of exposed the chemical hazards by other categories of disinfectants. The product does not required warning labels. It do not having the irritant effect over eye and can be absorbed by the skin, inhaled, or swallowed without having any harmful effects so it is much more compatible with the patients. The formulation of disinfectant is made up of nanospheres of oil droplets #106 mm that has suspended in water to create a nanoemulsion requiring only few amounts of the active ingredient, PCMX (parachloro metaxylenol). The nanospheres carried the surface charges that easily penetrate the surface charges on microorganisms' membranes-much like breaking through an electric fence. And "drowning" cells, allowed the formulation with PCMX to target and insert to the cell walls. As a result, at concentration levels 1-2 the PCMX is more effective orders of magnitude lower than those of other disinfectants; hence there are no toxic and irritants effects on human beings or animals and environment. Other microbial disinfectants having a large doses of their respective active ingredients to surround pathogen cell walls, which cause them to disintegrate. The formulation is a broad-spectrum disinfectant cleaner that is applied to any hard surface, including equipment, counters, walls, fixtures, and floors. One product can now take the place of many reducing product inventories and saving storage space 26


Cancer Therapy and Targeted Drug Delivery:

The effects of the formulation and particle composition of gadolinium (Gd)-containing lipid nanoemulsion (Gd-nanoLE) on the biodistribution of Gd after its intravenous (IV) injection in D1-179 melanoma-bearing hamsterz did evaluation for nanoemulsion application in cancer targeted neutron-capture therapy. In case of Bio-distribution data shows that Brij 700 and HCO-60 prolonged the retention of Gd in the blood and increased its accumulation in tumors. In case of the dermal application, the drug was predominantly localized in deeper part of the skin layers, with minimal systemic escape of formulation. This has been amounted to an absolute bioavailability found as 70.62%. Inhibition for P-glycoprotein efflux by D-tocopheryl polyethylene glycol 1000 succinate and labrasol would have been contributed to the enhancement of peroral bioavailability of PCL. This investigation provides the evidence on the localization containing highly molecular-weight, lipophilic drug, PCL, in dermis. Further, the nanoemulsion formulation has increased the peroral bioavailability significantly have more than 70%. The developed nanoemulsion formulation found safe and effective for both peroral and dermal delivery of PCL.  Camptothecin is a topoisomerase-I inhibitor that acting against a broad spectrum of cancers. However, its clinical application is limited by instability, toxicity and insolubility, the aim for the present study found to develop acoustically active nanoemulsions for camptothecin encapsulation to circumvent these types of delivery problems. The nanoemulsions was formulated by using liquid perfluorocarbons and coconut oil as the cores of the inner phase. These nanoemulsions have been stabilized by phospholipids and/or Pluronic F68 (PF68). The nanoemulsions were prepared at high mean droplet diameter of 220-420 nm. In these systems Camptothecin showed retarded drug release. Camptothecin in nanoemulsions with a lower oil concentration exhibited cytotoxicity against the melanomas and ovarian cancer cells. Confocal laser scanning microscopy confirmed nanoemulsion uptake into cells. Using a 1 MHz ultrasound in ranging, an increased release of camptothecin from the system with lower oil concentration could be established, illustrating a drug-targeting effect. The scientists have been done a general investigation that nanoemulsion which containing risperidone (RSP) to accomplish the delivery of drug to the brain via nasal route of administration. Risperidone nanoemulsion (RNE) and mucoadhesive nanoemulsion (RMNE) were characterized for drug content, pH determination, percentage transmittance, size, and zeta potential respectively. Biodistribution for RNE, RMNE, and risperidone solution (RS) in the brain and blood of Swiss albino rats following intranasal (i.n.) and intravenous (i.v.) administration was investigated using optimized technetium-labeled [(99 m) Tclabeled] RSP formulations. Gamma scientigraphy imaging brain of rat following i.v. and i.n. administrations was done to ascertain the localization of drug in brain. Higher drug transport efficiency (DTE%) and direct passes of nose to brain drug transport (direct transport percentage, DTP%) for mucoadhesive nanoemulsions clearly indicated more effective and best brain targeting of RSP amongst the prepared nanoemulsions. Studies conclusively that the rapid and larger extent of transport of RSP by RMNE (i.n.) when compared to RS (i.n.), RNE (i.n.), and RNE (i.v.) into the rat brain.  Another study reported the formulation of filter sterilizable formulation of paclitaxel emulsion using á-tocopherol as oil phase and á-tocopherylpolyethyleneglycol-1000 succinate (TGPS) and poloxamer 407 as emulsifiers. The formulation exhibited better efficacy and having more tolerable when studied in B16 melanoma tumor model in mice. Emulsion formulations also show great promises in cancer chemotherapy as vehicles for prolonging the drug release after intramuscular and intratumoral injection (W/O systems) and as a means of enhancing the transport of anti-cancer drugs via the lymphatic system. Positively charged nanoemulsions systems are usually expected to interact with negatively charged cell surfaces more efficiently, and this aspect of the positively charged nanoemulsions has been explored for possibility of oligonucleotides delivery to cancer cells. Photodynamic therapy (PDT) of cancer is based on the concept that certain photosensitizes can be localized in the neoplastic tissue, and subsequently, these photosensitizes can be activated with the appropriate wavelength (energy) of light to generate active molecular species such as free radicals and singlet oxygen that are toxic to cells and tissues 28,29 Various PDT therapies have reported two different vehicles for photosensitizers, a cremophor oil emulsion and DPPC (dipalmitoylphosphatidylcholine)liposomal vesicles. The reported pharmacokinetic studies clearly pointing that the former vehicle yields a significantly larger selectivity of tumor targeting, mainly as a consequence of an enhanced accumulation in the malignant lesion. Neutron Capture Therapy (NCT) is a binary radiation therapy modality that brings together two components that when kept separate had only minor effects on the cells. The preclinical studies have shown very positive effects with single dose and fractionated radiation in several rodent solid tumor models. Many widely used anticancer drugs, including anti-tumor alkylating agents and doxorubicin, have been shown improved response by PFCE co-administration. Also, local application of toxic doses of PFCEs resulted in the necrosis of cancer cells. This is especially promising in the treatment of cancers of the head and neck regions that are currently difficult to treat29



Nanoemulsions are attractive system for the use in the cosmetic, pharmaceuticals foods and pharmaceutical industries because of amount of very less surfactant, high stability against the coalescence, lower of toxicity or irritants characteristic. Due to their better permeability characteristic through skin the colloidal dispersions of solid nanoscale particulates have received the considerable attention. Moreover, the development of high throughout production make the potential for wide spread commercial used of nanoemulsion in consumer products and medical applications. In future, we can predict that nanoemulsion will become as ubiquitous as many polymer solution and solid particulate dispersions are today. 



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Received on 18.05.2017             Modified on 15.06.2017

Accepted on 01.07.2017            © RJPT All right reserved

Research J. Pharm. and Tech. 2017; 10(8): 2809-2818.

DOI: 10.5958/0974-360X.2017.00497.8