NANOEMULSION: An Effective Drug Carrier for the Management of Psoriasis
Rimmi Singh1*, Abhishek Chakravorty1, Priya Kumar2 and Ankita Chaturvedi3
1Lovely Faculty of Applied Medical Sciences, Lovely Professional University, Jalandhar, Punjab, India
2Department of Pharmaceutical Technology, Meerut institute of Engineering and Technology, Meerut, UP, India
3Department of Biotech, Utkal University, Bhubaneswar, Orissa, India
- *Corresponding Author:
- Rimmi Singh Lovely
Faculty of Applied Medical Sciences,
Lovely Professional University,
Jalandhar, Punjab, India.
Email: [email protected]
Received: 05/02/2015 Revised: 10/02/2015 Accepted: 15/02/2015
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Psoriasis, Dermatological disorder, Inflammatory.
Psoriasis is a chronic autoimmune inflammatory dermatological disorder [1-3]. Different genetic factors such as HLA-C genes and environmental factors (infection, stress, food or drugs) are considered as pathogenesis of psoriasis [4,5]. Psoriasis is a psychosocially, debilitating disorder that affect 1 to 3% of the population worldwide [6-9]. West African countries like Nigeria, Ghana, Mali, Senegal, Angola etc, have a lower prevalence of psoriasis (0.05 % to 1%) than the eastern countries like Kenya, Uganda, Tanzania (3%). Psoriatic arthropathy also seems higher in white populations (11% in USA) than in Asian (1% in Japan) or African persons, where the prevalence of HLA-B27 haplotype is low (3-6 % in certain African countries) . Psoriasis has a severe influence on physical and emotional well-being. It basically involves hyperproliferation of keratinocytes. The pathogenesis of psoriasis is related with disease-including T helper 1 (Th1) and T helper 17 (Th17) cells [11-17]. Maximum patient of psoriasis vulgaris are treated topically . However, several limitations are associated with the topical medication which acts as a barrier between topical medications and management of psoriasis [19,20]. One of the most important barriers is stratum corneum which reduces the bioavailability by restricting their absorption to a large extent, whereas in case of dermatological disorder topical application of active ingredient enhances therapeutic efficacy [21,22].
Presently, it has become important to ensure advancement and success in drug therapy along with the development of drug, because still the major causes for the failure of topical medications are :
1. Poor drug solubility,
2. Insufficient drug concentration due to poor absorption,
3. Rapid metabolism and elimination,
4. Drug distribution to other tissues combined with high drug toxicity
A promising strategy to avoid these drawbacks of drug is to develop a suitable drug carrier system and to achieve controlled and localized delivery of the active drug according to the specific demand of the therapy .
Transdermal drug delivery is a well-known route of administration, in which active ingredients is delivered via skin for systemic distribution [24,25]. It increases the bioavailability of drugs and reduces the adverse effects . Drug delivery via skin to the systemic circulation is suitable for a number of clinical conditions . Some important advantages of TDDS are mentioned below [28-32]:
• TDDS bypasses the first pass metabolism effect therefore suitable for low bioavailability drugs 
• Controlled drug delivery over extended period of time 
• Drug can be eliminated at any time by removing the transdermal patch [29-34]
• Total absence of gastrointestinal side effects like irritation and bowel ulcers which are invariably associated with oral delivery.
The three main routes by which drugs can primarily penetrate the skin are mentioned in Figure 1
Figure 1: Main routes of drug delivery through skin
As mentioned earlier stratum corneum acts as a barrier for topical therapy. For targeting the drug and to improve pharmacokinetics of drug, the primary skin barriers should be overcome . Some disadvantages of transdermal application are possibility of local skin irritation (due to an active substance or excipient) or absorption diversity due to differences in skin structure and thickness on different body parts . To avoid these problems and skin barrier effect, different modern techniques were developed .
Novel carriers such as liposome, niosome, microemulsion, nanoemulsion, nanostructured lipid carrier and ethosomes have indeed brought us closer to the goal of safe and efficacious treatment of the disease [23,36-38].
Nano/submicron emulsions are attracting researchers because of its increase skin permeation, prolonged action on the skin, and protection of the drug from instability. Nanoemulsions are most important and established novel carrier system which can be defined as isotropic, thermodynamically stable, transparent or translucent dispersions of oil and water stabilized by an interfacial film of surfactant molecules. Nanoemulsions are having the droplet size 20-500nm. Nanoemulsions have attracted the attention of researchers due to its easy method of preparation, high stability with increased bioavailability [23,39-43]. The advantages of nanoemusions are shown in Figure 2 [44-49].
Figure 2: Various advantages of Nanoemulsion
Types of Nanoemulsion
• O/W Nanoemulsion: Where oil droplets are dispersed in the continuous aqueous phase
• W/O Nanoemulsions: Where water droplets are dispersed in the continuous oil phase
• Bi-continuous Nanoemulsions: Where microdomains of oil and water are interdispersed within the system .
The interfacial tensions between oil and water are stabilized by addition of surfactants and cosourfactants.
Component of Nanoemulsion
Nanoemulsion contain four main component which are as follow [23,41]:
• Aqueous Phase
Decision of a suitable oil phase is vital as it influences the determination of other component of nanoemulsion, mostly in case of O/W nanoemulsion. Generally, the oil which has maximum solubilising potential for drug moiety is chosen as oily phase for the formulation of nanoemulsion. Maximum oil solubilizing potential is directly proportional to drug loading .
The surfactant should favournanoemulsification of the oily phase and should also acquire good solubilising potential for the hydrophobic drug compounds. Surfactants with HLB value <10 are hydrophobic (such as sorbitan monoesters) and high HLB (>10) surfactants are hydrophilic and further helps in formation of w/o nanoemulsion and o/w nanoemulsion respectively. The surfactant could be ionic or non-ionic but in few cases ionic surfactants are not preferred because of its toxicological concerns. Non-ionic water soluble surfactants are commonly used for nanoemulsion formulation. Few surfactants which are commonly used are lecithins, poloxamers and polysorbate 80 [23,33,48].
Surfactant alone cannot lower the oil-water interfacial tension adequately to yield a nanoemulsion due to which the addition of an amphiphillic short chain molecule or cosurfactant is compulsory. Hydrophilic cosurfactants preferably alcohols of intermediate chain length such as hexanol, pentanol and octanol, which are known to reduce the oil/water interface and allow the spontaneous formation of nanoemulsion [23,33].
Factors to Be Considered During Preparation of Nanoemulsion
• Surfactants must be precisely chosen so that an ultra-low interfacial tension (< 10-3 mN/m) can be accomplished at the oil/ water interface which is a prime prerequisite to deliver nanoemulsion .
• Concentration of surfactant must be sufficiently high so that it can provide sufficient surfactant molecules which required stabilizing the micro droplet to be created by ultra-low interfacial tension .
• The interface must be fluid enough to promote the formation of nanoemulsion .
Preparation of Nanoemulsion
The drug is dissolved in the lipophilic part (oil) of the nanoemulsion. The aqueous phase is combined with surfactant and a cosurfactant. The aqueous phase is added at a slow rate with gradual stirring until the system is transparent. The amount of surfactant and cosurfactant that can be incorporated shall be determined with the help of pseudo ternary phase diagram. Finally ultra sonicator can be used to achieve the desired range of dispersed globules. Then it is allowed to equilibrate. Gel may be prepared by adding a gelling agent. Most widely used gelling agent is carbomer [47,50].
Table 1: Research work of nanoemulsion for antipsoriatic activity
- Kawtar I, et al. Verrucous Psoriasis and Verrucous Lichen Associated With an Autoimmune Hepatitis. J ClinDiagn Res. 2014; 2:107.
- Lara T, et al. Severity of Psoriasis and Body Mass Index: The Cut off are Overweight Patients rather Than Obese Ones. J ClinExpDermatol Res. 2012; 3:165.
- Blum A, et al.ErythrodermicPustular Psoriasis Triggered by Subcutaneous Flu Vaccine. J Clin Case Rep. 2013; 3:255.
- Kozub P, et al. Management of Infliximab Treated Patients with Psoriasis Based On Infliximab Plasma Levels and Antibodies to Infliximab. J ClinExpDermatol Res. 2014; 5: 214.
- Rozin AP, Toledano K. New Sinusitis Associated Syndrome with Psoriasis and Periophthalmitis. J Clin Case Rep. 2013; 3: 306.
- Gandhi G, et al. Propensity for DNA Damage in Psoriasis Patients Genotyped for Two Candidate Genes. J CarcinogeneMutagene. 2010; 1:112
- Yu X, et al. Successful Treatment of Severe Psoriatic Arthritis and Psoriasis with Double Filtration Plasmapheresis. J Clin Cell Immunol. 2014; 5:222.
- Nakamura S, et al. Levels of Tumor Necrosis Factor-Alpha, Interleukin-6, and Interferon-Gamma during the Active Phases of Bechet’s Disease, Pustular Psoriasis, PalmoplantarPustulosis, and Stevens-Johnson Syndrome: A Pilot Study. J ClinExpDermatol Res. 2013; 4:175.
- Mayo KL, Gupta AK. A Case of Generalized Erythrodermic Psoriasis with Suicidal Ideation: A Unique Association. J ClinExpDermatol Res. 2011; 2:115.
- Diallo M. Psoriasis Epidemiology. J Clinic Case Reports. 2012; 2:e116.
- Antonucci VA, et al. Clubbing/Pseudoclubbing only in Fingernails Previously Affected by Psoriasis. J ClinExpDermatol Res. 2012; S6:005.
- Joseph EE, et al. A Pustular Psoriasis of the Face associated with a Perianal PyodermaGangrenosum: Same Nosologic Entity? J ClinExpDermatol Res. 2014; 5:230.
- Shimizu A, et al. Generalized Pustular Psoriasis Associated with Ulcerative Colitis. J ClinExpDermatol Res. 2013; 4:192.
- Guérard S, Pouliot. The Role of Angiogenesis in the Pathogenesis of Psoriasis: Mechanisms and Clinical Implications. J ClinExpDermatol Res. 2012; S2:007.
- Ibrahimbas Y, et al. Cellular Immune Response in Patients with Chronic Plaque Type Psoriasis: Evaluation of Serum Neopterin, Procalcitonin, Anti-Streptolysin O and C Reactive Protein Levels. J ClinExpDermatol. 2010; 1:107.
- Fthenakis A, et al.BiclonalGammopathy in a Patient taking Efalizumab for the Treatment of Psoriasis. J HematolThromb Dis. 2013; 1:106.
- Piérard GE, et al. Analytical Assessment of TNF-Antagonist Early Effects on Psoriasis: In Vivo Real-time Reflectance Confocal Microscopy and Skin Capacitance Mapping. J Med Diagn Meth. 2014; 3:165.
- Chiriac A, et al. New Onset of Psoriasis within Plaques of Vitiligo Treated with Narrow Band UVB: Case Report. Pigmentary Disorders. 2014; 1: 110.
- Anknegt R.Biologicals in the Treatment of Plaque Psoriasis: Drug Selection by Means of the SOJA Method. J Pharma Care Health Sys. 2014; 1:114.
- Clark BL, et al. Evaluation of a Retrospective Drug Utilization Review Program for the Treatment of Plaque Psoriasis: A Pilot Study. J Pharma Care Health Sys. 2015; 2:126.
- Jampilek J. Transdermal Application of Drugs and Techniques Affecting Skin Barrier. J BioequivAvailab. 2013; 5: 233-235.
- Pandey A, et al. Role of Surfactants as Penetration Enhancer in Transdermal Drug Delivery System. J Mol Pharm Org Process Res. 2014; 2: 1-10.
- Preeti K Suresh, et al. Novel topical drug carriers as a tool for treatment of psoriasis: Progress and advances. African Journal of Pharmacy and Pharmacology. 2013; 7: 138-147.
- Krishnaiah YSR. Pharmaceutical Technologies for Enhancing Oral Bioavailability of Poorly Soluble Drugs. J BioequivAvailab. 2010; 2: 28-36.
- Lakshmi PK, et al. Transdermal Permeation Enhancement of Lamotrigine Using Terpenes. J Pharma Care Health Sys. 2014; 1:103.
- Ahmed T, et al. Bioavailability and Interaction Potential of Atorvastatin and Losartan on Co-administration in Healthy Human Subjects. J BioequivAvailab. 2009; 1: 18-27.
- Parthasarathi D, et al. Analysis of Pharmacokinetic &Pharmacodynamic Models in Oral and Transdermal Dosage Forms. J BioequivAvailab. 2011; 3: 268-276.
- Branvold A, Carvalho M. Pain Management Therapy: The Benefits of Compounded Transdermal Pain Medication. J Gen Practice. 2014; 2: 1-8.
- Lin SL, et al. Enhancement of Transdermal Delivery of Indomethacin and Tamoxifen by Far-Infrared Ray- Emitting Ceramic Material (BIOCERAMIC): A Pilot Study. Transl Med. 2013; 3: 1-5.
- Meier-Davis SR, et al. Comparison of Metabolism of Donepezil in Rat, Mini-Pig and Human, Following Oral and Transdermal Administration, and in an in vitro Model of Human Epidermis. J Drug MetabToxicol. 2012; 3.
- Meier-Davis SR, et al. Absorption, Distribution and Excretion Pattern of Oral and Transdermal Donepezil Hydrochloride after Single and Repeated Administration to the Rat. J Drug MetabToxicol. 2012; 3.
- Malika V, et al. Nano-Carrier for Accentuated Transdermal Drug Delivery. J Develop Drugs 3: 1-9.
- Porras M, Solans C, Gonzalez C, Martinez A, Guinart A, et al. (2004) Studies of formation of w/o nanoemulsions. Col Surf. 2014; 249: 115-118.
- Delicou S, et al. Hyper-Acute Toxic Delirium in a Patient Using Transdermal Fentanyl. J Pain Relief. 2013; 2:125.
- Haritha, et al. A brief introduction to methods of preparation, applications and characterization of nanoemulsion drug delivery systems. IJRPB. 2013; 1: 25-28.
- Thakur Ajay, et al.Nanoemulsion in enhancement of bioavailability of poorly soluble drugs: A review.Pharmacophore. 2013; 4: 15-25.
- Shegokar R, Singh KK. Preparation, Characterization and Cell Based Delivery of Stavudine Surface Modified Lipid Nanoparticles. J NanomedBiotherapeutDiscov. 2012; 2: 2-9.
- Liu R. Nanostructured Lipid Carriers as the Most Promising Approach in Ocular Drug Delivery System. J NanomedBiotherapeutDiscov. 2012; 2: 1.
- Aliosmanoglu A, Basaran I. Nanotechnology in Cancer Treatment. J NanomedBiotherapeutDiscov. 2012 2:1-3.
- Caraglia M, et al. Nanotechnologies: New Opportunities for Old Drugs. The Case of Aminobisphosphonates. J NanomedicBiotherapeu Discover. 20111; 1: 1-2.
- Vaghasia N, Federman N. Liposomes for Targeting Cancer: One Step Closer to the Holy Grail of Cancer Therapeutics? J NanomedicBiotherapeu Discover. 2011; 1: 1-3.
- Said N El, et al. Nanoemulsion for Nanotechnology Size-Controlled Synthesis of Pd (II) Nanoparticles via Nanoemulsion Liquid Membrane. J MembraSci Technol. 2013; 3: 2-6.
- Salim N, et al. Phase Behaviour, Formation and Characterization of Palm-Based Esters Nanoemulsion Formulation containing Ibuprofen. J NanomedicNanotechnol. 2011; 2: 2-5.
- Rocha- Filho PA, et al. Influence of Lavander Essential Oil Addition on Passion Fruit Oil Nanoemulsions: Stability and In vivo Study. J NanomedNanotechnol. 2014; 5: 2-11.
- FaiyazShakeel, et al. Comparative Pharmacokinetic Profile of Aceclofenac from Oral and Transdermal Application Journal of Bioequivalence & Bioavailability. 2009; 1: 13-17.
- Kakumanu S, et al. A Self Assembling Nanoemulsion of Lovastatin (SANEL) Decreases Cholesterol Accumulation and Apob-100 Secretion Greater than Lovastatin alone a Hepg2 Cell Line. J NanomedNanotechol. 2012; 3: 1-4.
- Shakeel F, et al. Comparative Pharmacokinetic Profile of Aceclofenac from Oral and Transdermal Application. J BioequivAvailab. 2009; 1: 013-017.
- Rachmawati H, Haryadi BM. The Influence of Polymer Structure on the Physical Characteristic of Intraoral Film Containing BSA loaded Nanoemulsion. J NanomedNanotechnol. 2014; 5: 2-6.
- Silva HR, et al. Surfactant-based Transdermal System for Fluconazole Skin Delivery. J NanomedNanotechnol. 2014; 5: 1-10.
- Takegami S, et al. Application of 19F NMR Spectroscopy Using a Novel a-Tocopherol Derivative as a 19F NMR Probe for a Pharmacokinetic Study of Lipid Nano-Emulsions in Mice. Pharm Anal Acta. 2015; 6:339.
- Ali MdSajid, et al.Formulation,Characterization and In-vivo assessment of Topical Nanoemulsion of Betamethasone Valerate for psoriasis and dermatose, Int J Pharm. 2013; 3: 186-199.
- Ali MdSajid, et al. Topical nanoemulsion of turmeric oil for psoriasis: characterization, ex vivo and in vivo assessment., International Journal of Drug Delivery. 2012; 4: 184-197.
- Bioavailability and Interaction Potential of Atorvastatin and Losartan on Co-administration in Healthy Human Subjects.
- Ali MdSajid, et al. Formulation, Characterization and In-vivo study of nanoemulsion topical gel of beclomethasonedipropionate for psoriasis, World journal of pharmacy and pharmaceutical sciences. 2012; 1: 839-857.
- MdSarfarazAlama, et al. In vivo study of clobetasol propionate loaded nanoemulsion for topical application in psoriasis and atopic dermatitis. Drug Invention Today. 2013; 5: 8-12.