Nano-emulgel: Emerging as a Smarter Topical Lipidic Emulsion-based Nanocarrier for Skin Healthcare Applications

Author(s): Kumar Anand*, Subhabrata Ray, Mahfoozur Rahman, Adil Shaharyar, Rudranil Bhowmik, Rammohan Bera, Sanmoy Karmakar.

Journal Name: Recent Patents on Anti-Infective Drug Discovery

Volume 14 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: In recent decades, enormous efforts for different drug discovery processes have led to a number of drug molecules available today to overcome different challenges of the health care system. Unfortunately, more than half of these drugs are listed in either BCS (biopharmaceutical classification system) class II/ IV or both are eliminated from the development pipeline due to their limited clinical use. A nanotechnological approach bears much hope and lipoidal fabrication is found to be suitable for the delivery of such drugs. Nanoemulsion based gel i.e. nanoemulgel out of different nanolipoidal formulations has been found to be a suitable approach to successful drug delivery through topical routes. In past few years many herbal and synthetic active pharmaceutical ingredients (APIs) has been patented as nano sized emulsified gel for various therapeutic activities.

Methods: Nanoemulgel is basically an emulsion-based topical gel formulation, where nanosized emulsion globules can be prepared with the help of high energy or low energy methods and further converted into nanoemulgel by adding a suitable gelling agent. Nanoemulgel fabrication enlists various kinds of polymeric materials, surfactants and fatty substances of natural, synthetic and semi-synthetic nature with a globule size range from 5 to 500 nm.

Results: Nanoemulgel can be applicable to various acute and chronic diseases through topical routes.

Conclusion: Nanoemulgel preparations of many recently approved drugs are being used successfully in different areas of health care and have re-defined the significance of topical route of delivery as compared to other routes. However, along with various improvements in the current state of the delivery system, the safety factor needs to be taken into account by toxicological studies of the materials used in such formulations.

Keywords: Health care, topical route, BCS class II/IV, bioavailability, nanotechnology, nanoemulgel.

[1]
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol 2008; 26(11): 1261-8.
[2]
Tamjidi F, Shahedia M, Varshosazb J, Nasirpoura A. Nanostructured lipid carriers (NLC): A potential delivery system for bioactive food molecules. Innov Food Sci Emerg Technol 2103(19): 29-43.
[3]
Rahman M, Kumar V, Beg S, Sharma G, Katare OP, Anwar F. Emergence of liposome as targeted magic bullet for inflammatory disorders: current state of the art. Artif Cells Nanomed Biotechnol 2016; 44(7): 1597-608.
[4]
Kim BS, Won M, Lee KM, Kim CS. In vitro permeation studies of nanoemulsions containing ketoprofen as a model drug. Drug Deliv 2008; 15(7): 465-9.
[5]
Kale SN, Deore SL. Emulsion, micro-emulsion and nano emulsion. Sys Rev Pharm 2017; 8(1): 39-47.
[6]
Abd E, Benson HAE, Roberts MS, Grice JE. Minoxidil skin delivery from nanoemulsion formulations containing eucalyptol or oleic acid: enhanced diffusivity and follicular targeting. Pharmaceutics 2018; 10(1): 19.
[7]
Schroeter A, Engelbrecht T, Neubert RH, Goebel AS. New nanosized technologies for dermal and transdermal drug delivery. A review. J Biomed Nanotechnol 2010; 6(5): 511-28.
[8]
Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci 2006; 123-126: 369-85.
[9]
Rahman M, Akhter S, Ahmad J, Ahmad MZ, Beg S, Ahmad FJ. Nanomedicine-based drug targeting for psoriasis: potentials and emerging trends in nanoscale pharmacotherapy. Expert Opin Drug Deliv 2015; 12(4): 635-52.
[10]
Barry BW. Breaching the skin’s barrier to drugs. Nat Biotechnol 2004; 22(2): 165-7.
[11]
Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv 2010; 1(1): 109-31.
[12]
O López, M Cócera, Wertz PW, López-Iglesias C, de la Maza A. New arrangement of proteins and lipids in the stratum corneum cornified envelope. Biochim Biophys Acta Biomembr 2007; 1768(3): 521-9.
[13]
Panwar N. Upadhyay, M Bairagi, S Gujar, G Darwhekar emulgel. A review. Asian J Pharm Life Sci 2011; 1(3): 333-43.
[14]
Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces 2012; 100: 50-61.
[15]
Singh Y, Meher JG, Raval K, Khan FA, Chaurasia M, Jain NK, et al. Nanoemulsion: Concepts, development and applications in drug delivery. J Control Release 2017; 252: 28-49.
[16]
Calder PC. Hot topics in parenteral nutrition. Rationale for using new lipid emulsions in parenteral nutrition and a review of the trials performed in adults. Proc Nutr Soc 2009; 68(3): 252-60.
[17]
Manuel-y-Keenoy B, Nonneman L, De Bosscher H, Vertommen J, Schrans S, Klütsch K, et al. Effects of intravenous supplementation with alpha-tocopherol in patients receiving total parenteral nutrition containing medium- and long-chain triglycerides. Eur J Clin Nutr 2002; 56(2): 121-8.
[18]
Hippalgaonkar K, Majumdar S, Kansara V. Injectable lipid emulsions-advancements, opportunities and challenges. AAPS PharmSciTech 2010; 11(4): 1526-40.
[19]
Choudhury H, Gorain B, Karmakar S, Biswas E, Dey G, Barik R, et al. Improvement of cellular uptake, in vitro antitumor activity and sustained release profile with increased bioavailability from a nanoemulsion platform. Int J Pharm 2014; 460(1-2): 131-43.
[20]
Derle D, Sagar B, Sagar P. Microemulsion as a vehicle for transdermal permeation of nimesulide. Indian J Pharm Sci 2006; 68(5): 622-5.
[21]
Pawar KR, Babu RJ. Lipid materials for topical and transdermal delivery of nanoemulsions. Crit Rev Ther Drug Carrier Syst 2014; 31(5): 429-58.
[22]
Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics 2017; 9(4)9040037
[23]
Lee SY, Pung YY, Khor BK, Kong WE, Tan CT, Teo SY. Lipid-based delivery system for topical phenytoin. J Appl Pharm Sci 2016; 6(11): 14-20.
[24]
Dhawan B, Aggarwal G, Harikumar S. Enhanced transdermal permeability of piroxicam through novel nanoemulgel formulation. Int J Pharm Investig 2014; 4(2): 65-76.
[25]
Bajerski L, Michels LR, Colomé LM. Bender www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502016000300347- aff2 EA, Freddo RJ, Bruxel F, et al. The use of Brazilian vegetable oils in nanoemulsions: an update on preparation and biological applications. Braz J Pharm Sci 2016; 52(3): 347-63.
[26]
Deapsari, Erawati TM, Soeratri W. Penetration of ubiquinone (Q10) nanoemulsion using olive oil through rat skin. Int J Pharm Clin Res 2017; 9(2): 169-72.
[27]
Scholfield CR. Composition of soybean lecithin. Reprinted from. J Am Oil Chem Soc 1981; 58(10): 889-92.
[28]
van Hoogevest P, Wendel A. The use of natural and synthetic phospholipids as pharmaceutical excipients. Eur J Lipid Sci Technol 2014; 116(9): 1088-107.
[29]
Kato A, Ishibashi Y, Miyake Y. Effect of egg yolk lecithin on transdermal delivery of bunazosin hydrochloride. J Pharm Pharmacol 1987; 39(5): 399-400.
[30]
Hoeller S, Sperger A, Valenta C. Lecithin based nanoemulsions: A comparative study of the influence of non-ionic surfactants and the cationic phytosphingosine on physicochemical behaviour and skin permeation. Int J Pharm 2009; 370(1-2): 181-6.
[31]
Wu H, Ramachandran C, Weiner ND, Roessler BJ. Topical transport of hydrophilic compounds using water-in-oil nanoemulsions. Int J Pharm 2001; 220(1-2): 63-75.
[32]
Barry BW. Lipid-protein-partitioning theory of skin penetration enhancement. J Control Release 1991; 15(3): 237-48.
[33]
Lopes LB, VanDeWall H, Li HT, Venugopal V, Li HK, Naydin S, et al. Topical delivery of lycopene using microemulsions: enhanced skin penetration and tissue antioxidant activity. J Pharm Sci 2010; 99(3): 1346-57.
[34]
Khani S, Keyhanfar F, Amani A. Design and evaluation of oral nanoemulsion drug delivery system of mebudipine. Drug Deliv 2016; 23(6): 2035-43.
[35]
Syamala U. Development & optimization of allyl amine antifungal nanoemulgel using 23 factorial design: for the treatment of tinea pedis Eur Sci J
[http://dx.doi.org/10.19044/esj.2013.v9n10p%25p]
[36]
Pund S, Pawar S, Gangurde S, Divate D. Transcutaneous delivery of leflunomide nanoemulgel: Mechanistic investigation into physicomechanical characteristics, in vitro anti-psoriatic and anti-melanoma activity. Int J Pharm 2015; 487(1-2): 148-56.
[37]
Radhika PR, Guruprasad S. Nanoemulsion based emulgel formulation of lipophilic drug for topical delivery. Int J Pharm Tech Res 2016; 9(6): 210-23.
[38]
Sonal S. Appraisal of transdermal water-in-oil nanoemulgel of selegiline HCl for the effective management of parkinson’s disease: pharmacodynamic, pharmacokinetic, and biochemical investigations. AAPS PharmSciTech 2018; 19(2): 573-89.
[39]
Hauss DJ. Oral lipid-based formulations. Adv Drug Deliv Rev 2007; 59(7): 667-76.
[40]
Mortazavi S, Aboofazeli R. An investigation into the effect of various penetration enhancers on percutaneous absorption of piroxicam. Iran J Pharm Res 2003; 2: 135-40.
[41]
Pathan IB, Setty CM. Chemical penetration enhancers for transdermal drug delivery systems. Trop J Pharm Res 2009; 8(2): 173-9.
[42]
Srivastava M, Kohli K, Ali M. Formulation development of novel in situ nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Deliv 2016; 23(1): 154-66.
[43]
Ernoviya E, Masfria M, Sinaga KR, et al. Optimization and evaluation of topical ketoconazole nanoemulsion. Asian J Pharm Clin Res 2018; 11(5): 143-6.
[44]
Solè I, Maestro A, Gonzalez C, Solans C, Gutiérrez JM. Optimization of nano-emulsion preparation by low-energy methods in an ionic surfactant system. Langmuir 2006; 22(20): 8326-32.
[45]
Mason TG, Graves SM, Wilking JN, Lin MY. Extreme emulsification: Formation and structure of nanoemulsions. J Phys Condens Matter 2006; 9(1): 193-9.
[46]
Graves S, Meleson K, Wilking J, Lin MY, Mason TG. Structure of concentrated nanoemulsions. J Chem Phys 2005; 122(13)134703
[47]
Peng Jie, Dong Wu-jun, Li Ling, Xu JM, Jin DJ, Xia XJ, et al. Effect of high-pressure homogenization preparation on mean globule size and large diameter tail of oil-in-water injectable emulsions. J Food Drug Analysis 2015; 23: 828-35.
[48]
Kotta S, Khan AW, Ansari SH, Sharma RK, Ali J. Formulation of nanoemulsion: A comparison between phase inversion composition method and high-pressure homogenization method. Drug Deliv 2015; 22(4): 455-66.
[49]
Lovelyn C, Attama AA. Current state of nanoemulsions in drug delivery. J Biomater Nanobiotechnol 2011; 2: 626-39.
[50]
Leong TS, Wooster TJ, Kentish SE, Ashokkumar M. Minimising oil droplet size using ultrasonic emulsification. Ultrason Sonochem 2009; 16(6): 721-7.
[51]
Forgiarini A, Esquena J, González C, Solans C. Formation of nano-emulsions by low energy emulsification methods at constant temperature. Langmuir 2001; 17: 2076-83.
[52]
Porras M, Solans C, González C, Gutiérrez JM. Properties of water-in-oil (W/O) nano-emulsions prepared by a low-energy emulsification method. Colloids Surf A Physicochem Eng Asp 2008; 324(1-3): 181-8.
[53]
Chime SA, Kenechukwu FC, Attama AA. Nanoemulsions - Advances in formulation, characterization and applications in drug delivery In: Application of Nanotechnology in Drug Delivery Sezer AD, Ed London: IntechOpen 2014; pp. 76-126.
[54]
Komaiko JS, McClements DJ. Formation of food-grade nanoemulsions using low-energy preparation methods: A review of available methods. Compr Rev Food Sci Food Saf 2016; 15: 331-52.
[55]
Sengupta P, Chatterjee B. Potential and future scope of nanoemulgel formulation for topical delivery of lipophilic drugs. Int J Pharm 2017; 526(1-2): 353-65.
[56]
Pund S, Rasve G, Borade G. Ex vivo permeation characteristics of venlafaxine through sheep nasal mucosa. Eur J Pharm Sci 2013; 48(1-2): 195-201.
[57]
Schmolka IR. Artificial skin I. Preparation and properties of pluronic F-127 gels for the treatment of burns. J Biomed Mater Res 1972; 6: 571-82.
[58]
Barnes HA. Thixotropy-a review. J Non-Newt Fluid Mech 1997; 70(1-2): 1-33.
[59]
Arora R, Aggarwal G, Harikumar SL, Kaur K. Nanoemulsion based hydrogel for enhanced transdermal delivery of ketoprofen. Adv Pharm 2014; 2014: 1-2.
[60]
Bhura MRG, Bhagat KA, Shah SK. Formulation and evaluation of topical nano emulgel of adapalene World. J Pharm Sci 2015; 3(4): 1013-24.
[61]
Kaur A, Saxena Y, Bansal R, Gupta S, Tyagi A, Sharma RK, et al. Intravaginal delivery of polyphenon 60 and curcumin nanoemulsion gel. AAPS PharmSciTech 2017; 18(6): 2188-202.
[62]
Hosny KM, Banjar ZM. The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia. Expert Opin Drug Deliv 2013; 10(8): 1033-41.
[63]
Elosaily GH. Formulation and in vitro evaluation of nystatin nanoemulsion-based gel for topical delivery. J Am Sci 2012; 2012(8): 541-8.
[64]
Lakshmi P, Kumar GA. Nanosuspension technology: A review. Int J Pharm Pharm Sci 2010; 2(4): 35-40.
[65]
Hasenhuettl GL. Synthesis and commercial preparation of food emulsifiers.In: Food Emulsifiers and Their Applications. 2nd ed. New York: Springer Science Business Media 2008; pp. 11-37.
[66]
Araújo FA, Kelmann RG, Araújo BV, Finatto RB, Teixeira HF, Koester LS. Development and characterization of parenteral nanoemulsions containing thalidomide. Eur J Pharm Sci 2011; 42(3): 238-45.
[67]
Silva HD, Cerqueira MA, Vicente AA. Nanoemulsions for food applications: Development and characterization. Food Bioprocess Technol 2012; 5: 854-67.
[68]
Horne DS. Light scattering studies of colloid stability and gelation.In: New physicochemical techniques for the characterization of complex food systems. London: Blackie Academic & Professional 1995; pp. 240-67.
[69]
Saifullah M, Ahsan A, Shishir MRI. Production, stability and application of micro- and nanoemulsion in food production and food processing industry Emulsions: Nanotechnology in the AgriFood Industry. London: Academic press, Elsevier Inc. 2016; Vol. 3: pp. 405-42.
[70]
Chiesa M, Garg J, Kang YT, Chen G. Thermal conductivity and viscosity of water-in-oil nanoemulsions. Colloids Surf A Physicochem Eng Asp 2008; 326(1-2): 67-72.
[71]
Lakshmana PS, Sharvanan SP, Aravindan S, Bhuvaneswari A, Manikandan V. Nanoemulgel for transdermal delivery of cyclobenzaprine hydrochloride: design, characterization and in vitro studies. Nov Appr Drug Des Dev 2017; 1(5): 555-75.
[72]
Jones DS, Woolfson AD, Brown AF, Coulter WA, McClelland C, Irwin CR. Design, characterisation and preliminary clinical evaluation of a novel mucoadhesive topical formulation containing tetracycline for the treatment of periodontal disease. J Control Release 2000; 67(2-3): 357-68.
[73]
Majithiya RJ, Ghosh PK, Umrethia ML, Murthy RSR. Thermoreversible mucoadhesive gel for nasal delivery of sumatriptan 2006.
[74]
Kumar L, Verma R. In vitro evaluation of topical gel prepared using natural polymer. Int J Drug Deliv 2010; 2: 58-63.
[75]
Kaur G, Bedi PMS, Narang JK. Topical nanoemulgel: a novel pathway for investigating alopecia. J Nanomed Nanotechnol 2017; 8: 472.
[76]
Srdan V. Stankov. Definition of inflammation, causes of inflammation and possible anti-inflammatory strategies. Open Inflamm J 2012; 5: 1-9.
[77]
Dasgupta S, Ghosh SK, Ray S, Kaurav SS, Mazumder B. In vitro & in vivo studies on lornoxicam loaded nanoemulsion gels for topical application. Curr Drug Deliv 2014; 11(1): 132-8.
[78]
Mustafa A, Eid M, Elmarzugi NA, El-Enshasy HA. A review on the phytopharmacological effect of Swietenia macrophylla. Int J Pharm Pharm Sci 2013; 5(Suppl. 3): 47-53.
[79]
Eid AM, El-Enshasy HA, Aziz R, Elmarzugi NA. Preparation, characterization and anti-inflammatory activity of Swietenia macrophylla nanoemulgel. J Nanomed Nanotechnol 2014; 5(2): 190.
[80]
Jaganmohan S. Nanomiemgel - a novel drug delivery system for topical application - in vitro and in vivo evaluation. PLoS One 2014; 9(12)e115952
[81]
Rahman BS, Anwar F, Al-Abbasi FA, Kumar V. Nanotechnology-based nano bullets in anti-psoriatic drug delivery: state of the art nanoscience in dermatology. UK: Elsevier 2016; pp. 157-66.
[82]
Sarfaraz MA, Sajid M, Alam N, Alam MI. Design and characterization of nanostructure topical gel of betamethasone dipropionate for psoriasis. J Appl Pharm Sci 2012; 2(10): 148-58.
[83]
Herrmann ML, Schleyerbach R, Kirschbaum BJ. Leflunomide: an immunomodulatory drug for the treatment of rheumatoid arthritis and other autoimmune diseases. Immunopharmacology 2000; 47(2-3): 273-89.
[84]
Kaltwasser JP. Leflunomide in psoriatic arthritis. Autoimmun Rev 2007; 6(8): 511-4.
[85]
Elewski BE, Hay RJ. Update on the management of onychomycosis: highlights of the Third Annual International Summit on Cutaneous Antifungal Therapy. Clin Infect Dis 1996; 23(2): 305-13.
[86]
Mahtab A, Anwar M, Mallick N, Naz Z, Jain GK, Ahmad FJ. Transungual delivery of ketoconazole nanoemulgel for the effective management of onychomycosis. AAPS PharmSciTech 2016; 17(6): 1477-90.
[87]
Elmataeeshy ME, Sokar MS, Bahey-El-Din M, Shaker DS. Enhanced transdermal permeability of Terbinafine through novel nanoemulgel formulation; Development, in vitro and in vivo characterization. Future J Pharm Sci 2018; 4(1): 18-28.
[88]
Aparna C. Enhanced transdermal permeability of telmisartan by a novel nanoemulsion gel. Int J Pharm Pharm Sci 2015; 7(4): 335-42.
[89]
Parhi R, Terapalli BR, Teja BB. Formulation and in vivo evaluation of minoxidil topical gel. Turk J Pharm Sci 2014; 11: 153-62.
[90]
Usmania BA, Kataria MK. Minoxidil emulgel for androgenic alopecia: A literature review including patents. Int J Pharm Drug Anal 2017; 5(3): 49-58.
[91]
Olsen EA, Dunlap FE, Funicella T, Koperski JA, Swinehart JM, Tschen EH, et al. A randomized clinical trial of 5% topical minoxidil versus 2% topical minoxidil and placebo in the treatment of androgenetic alopecia in men. J Am Acad Dermatol 2002; 47(3): 377-85.
[92]
Rani D, Singh C, Kumar A, Sharma VK. Formulation development and in vitro evaluation of minoxidil bearing glycerosomes. AJBR 2016; 4: 27-37.
[93]
Sunitha S, Wankar J, Ajimera T. Design, Development and evaluation of nanoemulsion and nanogel of itraconazole for transdermal delivery. J Sci Res Pharm 2014; 3(1): 6-11.
[94]
Aithal GC, Nayak UY, Mehta C, Narayan R, Gopalkrishna P, Pandiyan S, et al. Localized in situ nanoemulgel drug delivery system of quercetin for periodontitis: development and computational simulations. Molecules 2018; 23(6): 1363.
[95]
Jeengar MK, Rompicharla SV, Shrivastava S, Chella N, Shastri NR, Naidu VG, et al. Emu oil based nano-emulgel for topical delivery of curcumin. Int J Pharm 2016; 506(1-2): 222-36.
[96]
Mahesh B, Vasanth KP, Gowda DV, Atul S, Raghundan HV, Chetan SG. Enhanced permeability of cyclosporine from a transdermally applied nanoemulgel. Der Pharm Sinica 2015; 6: 69-7.
[97]
Mohammad W, Abdus S, Iram Z, Anubha K, Mohd A, Mohib K. Formulation development Ex-vivo and in-vivo evaluation of nanoemulsion for transdermal delivery of glibenclamide. 2013; 5(Suppl 4): 747-54.
[98]
Singh BP, Kumar B, Jain SK, Shafaat K. Development and characterization of a nanoemulsion gel formulation for transdermal delivery of carvedilol. Int J Drug Dev Res 2012; 4(1): 151-61.
[99]
Drais HK, Hussein AA. Formulation characterization and evaluation of meloxicam nanoemulgel to be used topically. Iraqi J Pharm Sci 2017; 26(1)
[100]
Mulia K, Ramadhan RMA, Krisanti EA. Formulation and characterization of nanoemulgel mangosteen extract in virgin coconut oil for topical formulation. MATEC Web of Conferences 2018; 156: 01013.
[101]
Harwansh RK, Mukherjee PK, Bahadur S, Biswas R. Enhanced permeability of ferulic acid loaded nanoemulsion based gel through skin against UVA mediated oxidative stress. Life Sci 2015; 141: 202-11.
[102]
Pathak MK, Chhabra G, Pathak K. Design and development of a novel pH triggered nanoemulsified in-situ ophthalmic gel of fluconazole: ex-vivo transcorneal permeation, corneal toxicity and irritation testing. Drug Dev Ind Pharm 2013; 39(5): 780-90.
[103]
Singh KK, Tatke PA, Dhuru S. Neem oil contraceptive formulations. WO2006082596A2 (2006).
[104]
Novartis AG. Diclofenac in emulsion-gel form EP2055298A1 (2009).
[105]
Bhushanm RS, Shafiqm S, Jay K, Jitendra P. Stable pharmaceutical composition of diclofenac. US20120093882A1 (2012).
[106]
James R. Nanoemulsion containing Composition having anti- inflammatory activity. WO2008051186A2 (2008).
[107]
Azeem A, Rizwan M, Ahmad FJ, Iqbal Z, Khar RK, Aqil M, et al. Nanoemulsion components screening and selection: a technical note. AAPS PharmSciTech 2009; 10(1): 69-76.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 1
Year: 2019
Page: [16 - 35]
Pages: 20
DOI: 10.2174/1574891X14666190717111531

Article Metrics

PDF: 10