|Year : 2019 | Volume
| Issue : 4 | Page : 290-294
Nanotechnology in pediatric dermatology
Sandipan Dhar1, Ramkumar Rammoorthy2, Samujjala Deb3, Deepak Parikh4
1 Department of Pediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India
2 Department of Pediatric Dermatology, Kanchi Kamakoti Childs Trust Hospital, Chennai, Tamil Nadu, India
3 Department of Dermatology, Bardhaman Medical College, Kolkata, West Bengal, India
4 Department of Pediatric Dermatology, Wadia Children Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||30-Sep-2019|
Dr Sandipan Dhar
Flat 9C, Palazzo, 35, Panditia Road, Kolkata- 700 029
Source of Support: None, Conflict of Interest: None
Nanotechnology is the manipulation of material with size <100 μ. Application of nanotechnology in medicine is also known as nanomedicine. Nanotechnology has found varied applications in medicine, ranging from diagnostic devices, contrast agents, tools for analysis, and most importantly in the field of drug delivery.
Keywords: Nanotechnology, pediatric dermatology, nanomedicine, particle size
|How to cite this article:|
Dhar S, Rammoorthy R, Deb S, Parikh D. Nanotechnology in pediatric dermatology. Indian J Paediatr Dermatol 2019;20:290-4
|How to cite this URL:|
Dhar S, Rammoorthy R, Deb S, Parikh D. Nanotechnology in pediatric dermatology. Indian J Paediatr Dermatol [serial online] 2019 [cited 2020 Apr 5];20:290-4. Available from: http://www.ijpd.in/text.asp?2019/20/4/290/268404
| Introduction|| |
Nanomedicine is the field of science dealing with the application of nanotechnology in medicine. Nanotechnology encompasses the science behind the manipulation of particles of size <100 μ. The concepts of nanotechnology were put forward by the famed physicist Richard Feynman. The term “nano-technology” was used in the year 1974 by Norio Taniguchi. Since then, this field has expanded exponentially and has found widespread application in all aspects of life. In medicine too, nanotechnology has revolutionized the understanding and application of biological sciences.
In nanomedicine, there has been extensive interest and research for applications in newer techniques for drug delivery, diagnostic modalities, contrast agents, and analytical tools.
In pediatric dermatology too, there has been interest in applying nanotechnology to aid in the diagnosis and management of various conditions.
This review seeks to explore this nascent concept of nanotechnology in the field of dermatology, potentially pediatric dermatology.
| Types of Nanoparticles|| |
Nanoparticles are substances measuring between 1 nm and 100 nm. They can be either organic or inorganic. They can also be further classified on the basis of their size, shape, surface, or physicochemical properties.
They can also be differentiated into rigid and malleable types. Malleable nanoparticles can be made to change their shape by stress or on coming in contact with other substances.
The various malleable and rigid particles are elaborated in [Table 1].
| Future Directions in Nanodermatology Research|| |
Nanodermatology is being explored in a multitude of ways to evaluate its utility in various areas.
Some of the avenues being explored are the field of consumer products such as sunscreens, dressings, antimicrobials and insect repellants, diagnostic equipment for real-time visualization of tumors and sentinel lymph nodes, real-time diagnosis of infections and malignancies, and minimally invasive biopsies, and lastly the most important application in the field of therapeutics such as antimicrobials, fillers, corticosteroids, vaccines, and skin treatments with optical, magnetic, thermal, and radiofrequency devices.
Thus, nanodermatology has made a foray into every conceivable aspect and thus shows a very promising future.
| Mode of Action of Nanomaterials|| |
The absorption of substance across the skin is under the control of the epidermal barrier. Thus, it has to cross the various layers of the skin before it can be absorbed into the systemic circulation. This is a tightly controlled and highly regulated process. Sometimes, products such as cosmeceutical are not required to be absorbed into the systemic circulation but have to be able to be absorbed into the skin. Some of the mechanisms that have been described for the transepidermal absorption are the transfollicular, transcellular, and intercellular pathways.,,
The maximum size that can permeate through the skin is around 400 Daltons. The skin by itself acts as a mechanical barrier which is porous to nano-sized particles and is traversed by a plenty of semi-circular-to-circular channels. A number of research publications have demonstrated that these pores often measure between 0.4 and 36.0 nm. Moreover, different molecules which are passively absorbed pass through these channels. It has thus been shown that nanoparticles actively participate in movement through these channels.,
Some of the systems that are being used to transport substances in topical formulations are liposomes and noisomes, cyclodextrins, microparticles, and nanoparticles. These nanoparticles are the most promising as they have high levels of physicochemical stability along with no technological limitations and can be used in various formulations.,,
Moreover, it is not just the delivery of topical formulations that have found nanoparticles to be effective. Nanoparticles (especially liposomes) are being tried in drug delivery for malignancies such as skin cancers. Thus, these nanoparticles can encapsulate the drug, enhancing drug absorption and delivery to the target site while minimizing the toxicity of the same.
| Applications in Pediatric Dermatology|| |
Nanotechnology has found wide use in the field of photoprotection. The compounds which have been developed are nanoparticle titanium dioxide and zinc oxide.
The advantage of these nano-formulations is that they cause less skin whitening as compared to conventional organic sunscreen agents, thus making them more effective in absorbing or deflecting ultraviolet radiation as well as better esthetic acceptability among caregivers.
One of the concerns which has come up is the absorption of these nanoparticles if the skin barrier is damaged in any way, thus requiring further studies and evaluations till they become accepted as mainstream products.,,,,,,,,,,,
Another concern is regarding the generation of free radicals and reactive oxygen species by these nanoparticles on exposure to ultraviolet radiation. These free radicals can damage DNA, thus causing mutations as well as irreversible cell damage.,
Therapeutics for inflammatory disorders
This has a very promising potential in the management of one of the most common pediatric dermatologic disorders such as atopic dermatitis. In atopic dermatitis, there is an impairment of the barrier function of the skin. This damaged barrier needs to be repaired with the help of emollients and creams and at the same time prevent further damage to it from the irritant effect of the topical medication.
Nanoparticles have found their way in this scenario due to the fact that nanoparticle-containing barrier creams and emollients are more effective than lipid-containing moisturizers against loss of water and also decrease the chance of developing contact dermatitis.
Similarly, nanoparticle-containing corticosteroids have also found to be more beneficial than conventional preparations. They reach the target site of action easily and the chance of developing steroid-induced side effects such as atrophy are also less. Similar results have also been demonstrated with liposomal delivery formulations of cyclosporine A and tacrolimus as well.,
This is another important area of nanotechnology research and development. A nanoparticle-containing formulation of chlorhexidine gluconate (Nanochlorex®) was found to have an earlier onset of antibacterial effect due to enhanced absorption along with extended duration of action due to slow and gradual liberation from the nanoparticles.,
One of the more common and widely used antibacterial-containing nanoparticles in the recent times is nanosilver and there are plenty of products currently available in the markets.,
Therapeutics in pilosebaceous dermatoses
The sebaceous glands open into the hair follicles. As has been previously discussed, transfollicular route is an important pathway for percutaneous absorption. Thus, it is more than natural that nanoparticles have been evaluated for the management of disorders of the pilosebaceous units.
In pediatric dermatology, one of the most common complaints in the growing up years is that of or acne vulgaris. In a study done by Rolland et al., adapalene when conjugated with polymerized particles such as poly(lactic acid) and poly(lactic-co-glycolic acid), the intrafollicular drug delivery and distribution was found to be much better in comparison to conventional formulations.
Other nanoparticles which have been studied for intrafollicular delivery include liposomes, solid lipid nanoparticles, and polymerized nanoparticles.
Other retinoids which have been evaluated for nanoparticle formulations include liposomal retinol and tretinoin.,
The greatest advantage of these nano-formulations is decreased irritation due to retinoid as well as enhanced drug delivery and minimal systemic side effect. Both these factors together enhance patient compliance which is of utmost importance, especially in the pediatric age group.
These advancements in acne therapy have not been limited to retinoids alone. It has been evaluated for other drugs as well such as benzoyl peroxide creams, benzoyl peroxide facewash, and antiandrogens.,,
Therapeutics for scalp dermatoses
Based on the principle of enhanced absorption of nanoparticles across the intrafollicular pathway, formulations containing these have a better suitability as compared to aqueous and alcoholic solutions in the treatment of conditions such as alopecia areata and androgenetic alopecia.
Encapsulation of hinokitiol, a substance commonly used in hair tonics, substantially increased the transition from telogen to anagen phase for the hair in comparison to conventional solutions for the same. Similarly, Minoxidil when formulated with polyethylene glycol nanoparticles had improved permeability in the hair follicles.
Novel areas for the treatment of alopecia areata are liposomal formulations of cyclosporine A and have been experimentally tried in rats.
| Nanotechnology in Diagnostics|| |
Nanoparticles have found enhanced interest in the field of diagnostics due to the fact that smaller quantities of tissue samples are required along with higher sensitivity, specificity, and rapidity of the method for detection.
The two promising modalities that are currently being extensively studied are optical fiber and quantum dots.
Fabrics made from optical fibers have great application in pediatric dermatology. They can be used in a number of situations such as mapping of nevi and studying the course of diseases such as atopic dermatitis.
Quanta are fluorescent particles. They can be used to locate malignancies and also sentinel lymph nodes. Thus, they are being evaluated in the diagnosis of various malignancies.
| Risk of Nanotechnology|| |
Nanotechnology and nanomedicine are relatively new fields of scientific research. Thus, extensive data regarding the efficacy and safety are yet to be determined.
Since the materials being used are in the range of nanometric scale, they are prone to chemical volatility; there is a chance that there may be a possibility of tissue and cellular damage. There is still scarce data describing the environmental and biological interactions with nanoparticles. The most important concerns are regarding the life cycle of these particles in the body, the various routes of exposure, and lastly their behavior inside the human body.
Furthermore, there is no data correlating the effects of these particlesin vitro(cellular and molecular) andin vivo(animal studies).
A study by Crosera M et al. is one of the few studies which has attempted to establish the various physicochemical properties of these nanoparticles and their interactions in animal models. However, still there is scarce data elucidating the immediate toxic effect and long-term oncogenic potential of nanoparticles in comparison to asbestos, which was proven to have a definite role in the development of mesothelioma on chronic exposure., It thus becomes imperative to determine the exact pharmacokinetics/pharmacodynamics, toxicities, efficacy, and lastly benefits. Thus, there is still a long way to go with adequate studies before nanoparticles and nanomedicine become accepted in mainstream medicine.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Freitas RA Jr. Nanomedicine: Basic Capabilitie. Vol. I. New York: McGraw-Hill;1999.
Papakostas D, Rancan F, Sterry W, Blume-Peytavi U, Vogt A. Nanoparticles in dermatology. Arch Dermatol Res 2011;303:533-50.
Jung S, Otberg N, Thiede G, Richter H, Sterry W, Panzner S, et al.
Innovative liposomes as a transfollicular drug delivery system: Penetration into porcine hair follicles. J Invest Dermatol 2006;126:1728-32.
Peek LJ, Middaugh CR, Berkland C. Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 2008;60:915-28.
de Vries JJ, Bungener L, Ter Veer W, van Alphen L, van der Ley P, Wilschut J, et al.
Incorporation of LpxL1, a detoxified lipopolysaccharide adjuvant, in influenza H5N1 virosomes increases vaccine immunogenicity. Vaccine 2009;27:947-55.
Ludwig C, Wagner R. Virus-like particles-universal molecular toolboxes. Curr Opin Biotechnol 2007;18:537-45.
Mahe B, Vogt A, Liard C, Duffy D, Abadie V, Bonduelle O, et al.
Nanoparticle-based targeting of vaccine compounds to skin antigen-presenting cells by hair follicles and their transport in mice. J Invest Dermatol 2009;129:1156-64.
Chirico F, Fumelli C, Marconi A, Tinari A, Straface E, Malorni W, et al.
Carboxyfullerenes localize within mitochondria and prevent the UVB-induced intrinsic apoptotic pathway. Exp Dermatol 2007;16:429-36.
Kato S, Taira H, Aoshima H, Saitoh Y, Miwa N. Clinical evaluation of fullerene-C60 dissolved in squalane for anti-wrinkle cosmetics. J Nanosci Nanotechnol 2010;10:6769-74.
Villalonga-Barber C, Micha-Screttas M, Steele BR, Georgopoulos A, Demetzos C. Dendrimers as biopharmaceuticals: Synthesis and properties. Curr Top Med Chem 2008;8:1294-309.
Venuganti VV, Perumal OP. Poly (amidoamine) dendrimers as skin penetration enhancers: Influence of charge, generation, and concentration. J Pharm Sci 2009;98:2345-56.
Kristl J, Teskac K, Grabnar PA. Current view on nanosized solid lipid carriers for drug delivery to the skin. J Biomed Nanotechnol 2010;6:529-42.
Saupe A, Wissing SA, Lenk A, Schmidt C, Müller RH. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) - Structural investigations on two different carrier systems. Biomed Mater Eng 2005;15:393-402.
Schäfer-Korting M, Mehnert W, Korting HC. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev 2007;59:427-43.
Walther C, Meyer K, Rennert R, Neundorf I. Quantum dot-carrier peptide conjugates suitable for imaging and delivery applications. Bioconjug Chem 2008;19:2346-56.
Zhou M, Nakatani E, Gronenberg LS, Tokimoto T, Wirth MJ, Hruby VJ, et al.
Peptide-labeled quantum dots for imaging GPCRs in whole cells and as single molecules. Bioconjug Chem 2007;18:323-32.
Nasir A. Nanodermatology: A glimpse of caution just beyond the horizon - Part II. Skin Therapy Lett 2010;15:4-7.
Nasir A, Friedman A, Wang S (Eds). Nanotechnology in Dermatology. Springer, New York ; 2015. p. 74.
Gupchup GV, Zatz J. Target delivery to pilosebaceous structures. Cosmet Toiler 1997;112:79-88.
Abraham MH, Chadha HS, Mitchell RC. The factors that influence skin permeation of solutes. J Pharm Pharmacol 1955;47:8-16.
Cevc G, Blume G, Schätzlein A, Gebauer D, Paul A. The skin: A pathway for systemic treatment with patches and lipid based carriers. Adv Drug Deliv Rev 1996;18:349-78.
Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci 2001;14:101-14.
Rogers K. Controlled release technology and delivery systems. Cosmet Toiler 1999;114:53-60.
Nacht S. Encapsulation and other topical delivery systems: A review of the state of-the-art for controlled topical delivery. Cosmet Toiler 1995;110:25-30.
Wang SQ, Tooley IR. Photoprotection in the era of nanotechnology. Semin Cutan Med Surg 2011;30:210-3.
Tan MH, Commens CA, Burnett L, Snitch PJ. A pilot study on the percutaneous absorption of microfine titanium dioxide from sunscreens. Australas J Dermatol 1996;37:185-7.
Dussert AS, Gooris E, Hemmerle J. Characterization of the mineral content of a physical sunscreen emulsion and its distribution onto human stratum corneum. Int J Cosmet Sci 1997;19:119-29.
Lademann J, Weigmann H, Rickmeyer C, Barthelmes H, Schaefer H, Mueller G, et al.
Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Pharmacol Appl Skin Physiol 1999;12:247-56.
Schulz J, Hohenberg H, Pflücker F, Gärtner E, Will T, Pfeiffer S, et al.
Distribution of sunscreens on skin. Adv Drug Deliv Rev 2002;54 Suppl 1:S157-63.
Gontier E, Ynsa MD, Biro T, Hunyadij J, Kiss B, Gáspár K, et al
. Is there penetration of Titania nanoparticles in sunscreens through skin? A comparative electron and ion microscopy study. Nanotoxicology 2008;2:218-31.
Cross SE, Innes B, Roberts MS, Tsuzuki T, Robertson TA, McCormick P, et al.
Human skin penetration of sunscreen nanoparticles: In-vitro
assessment of a novel micronized zinc oxide formulation. Skin Pharmacol Physiol 2007;20:148-54.
Mavon A, Miquel C, Lejeune O, Payre B, Moretto P.In vitro
percutaneous absorption andin vivo
stratum corneum distribution of an organic and a mineral sunscreen. Skin Pharmacol Physiol 2007;20:10-20.
Pinheiro T, Pallon J, Alves LC, Veríssimo A, Filipe P, Silva JN. The influence of corneocyte structure on the interpretation of permeation profiles of nanoparticles across skin. Nucl Instrum Methods Phys Res B 2007;260:119-23.
Zvyagin AV, Zhao X, Gierden A, Sanchez W, Ross JA, Roberts MS, et al.
Imaging of zinc oxide nanoparticle penetration in human skinin vitro
and in vivo
. J Biomed Opt 2008;13:64031.
Sadrieh N, Wokovich AM, Gopee NV, Zheng J, Haines D, Parmiter D, et al.
Lack of significant dermal penetration of titanium dioxide from sunscreen formulations containing nano-and submicron-size TiO2 particles. Toxicol Sci 2010;115:156-66.
Filipe P, Silva JN, Silva R, Cirne de Castro JL, Marques Gomes M, Alves LC, et al.
Stratum corneum is an effective barrier to TiO2 and ZnO nanoparticle percutaneous absorption. Skin Pharmacol Physiol 2009;22:266-75.
Durand L, Habran N, Henschel V, Amighi K.In vitro
evaluation of the cutaneous penetration of sprayable sunscreen emulsions with high concentrations of UV filters. Int J Cosmet Sci 2009;31:279-92.
Johnston HJ, Hutchison GR, Christensen FM, Peters S, Hankin S, Stone V, et al.
Identification of the mechanisms that drive the toxicity of TiO2 particulates: The contribution of physicochemical characteristics. Part Fibre Toxicol 2009;6:33.
Hirakawa K, Mori M, Yoshida M, Oikawa S, Kawanishi S. Photo-irradiated titanium dioxide catalyzes site specific DNA damage via generation of hydrogen peroxide. Free Radic Res 2004;38:439-47.
de Fine Olivarius F, Hansen AB, Karlsmark T, Wulf HC. Water protective effect of barrier creams and moisturizing creams: A newin vivo
test method. Contact Dermatitis 1996;35:219-25.
Santos Maia C, Mehnert W, Schaller M, Korting HC, Gysler A, Haberland A, et al.
Drug targeting by solid lipid nanoparticles for dermal use. J Drug Target 2002;10:489-95.
Erdogan M, Wright JR Jr., McAlister VC. Liposomal tacrolimus lotion as a novel topical agent for treatment of immune-mediated skin disorders: Experimental studies in a murine model. Br J Dermatol 2002;146:964-7.
Egbaria K, Ramachandran C, Weiner N. Topical application of liposomally entrapped cyclosporin evaluated byin vitro
diffusion studies with human skin. Skin Pharmacol 1991;4:21-8.
Lboutounne H, Chaulet JF, Ploton C, Falson F, Pirot F. Sustained ex vivo
skin antiseptic activity of chlorhexidine in poly (epsilon-caprolactone) nanocapsule encapsulated form and as a digluconate. J Control Release 2002;82:319-34.
Lboutounne H, Faivre V, Falson F, Pirot F. Characterization of transport of chlorhexidine-loaded nanocapsules through hairless and Wistar rat skin. Skin Pharmacol Physiol 2004;17:176-82.
Chen X, Schluesener HJ. Nanosilver: A nanoproduct in medical application. Toxicol Lett 2008;176:1-2.
Rolland A, Wagner N, Chatelus A, Shroot B, Schaefer H. Site-specific drug delivery to pilosebaceous structures using polymeric microspheres. Pharm Res 1993;10:1738-44.
Jenning V, Gysler A, Schäfer-Korting M, Gohla SH. Vitamin A loaded solid lipid nanoparticles for topical use: Occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm 2000;49:211-8.
Patel VB, Misra A, Marfatia YS. Topical liposomal gel of tretinoin for the treatment of acne: Research and clinical implications. Pharm Dev Technol 2000;5:455-64.
Queille-Roussel C, Poncet M, Mesaros S, Clucas A, Baker M, Soloff AM, et al.
Comparison of the cumulative irritation potential of adapalene gel and cream with that of erythromycin/tretinoin solution and gel and erythromycin/isotretinoin gel. Clin Ther 2001;23:205-12.
Bernard E, Dubois JL, Wepierre J. Importance of sebaceous glands in cutaneous penetration of an antiandrogen: Target effect of liposomes. J Pharm Sci 1997;86:573-8.
Münster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, et al.
RU 58841-myristate – Prodrug development for topical treatment of acne and androgenetic alopecia. Pharmazie 2005;60:8-12.
Bikowski J, Del Rosso JQ. Benzoyl peroxide microsphere cream as monotherapy and combination treatment of acne. J Drugs Dermatol 2008;7:590-5.
Tsujimoto H, Hara K, Tsukada Y, Huang CC, Kawashima Y, Arakaki M, et al.
Evaluation of the permeability of hair growing ingredient encapsulated PLGA nanospheres to hair follicles and their hair growing effects. Bioorg Med Chem Lett 2007;17:4771-7.
Shim J, Seok Kang H, Park WS, Han SH, Kim J, Chang IS, et al.
Transdermal delivery of mixnoxidil with block copolymer nanoparticles. J Control Release 2004;97:477-84.
Vogt A, Combadiere B, Hadam S, Stieler KM, Lademann J, Schaefer H, et al.
40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+cells after transcutaneous application on human skin. J Invest Dermatol 2006;126:1316-22.
Hia J, Nasir A. Photonanodermatology: The interface of photobiology, dermatology and nanotechnology. Photodermatol Photoimmunol Photomed 2011;27:2-9.
Eden JG, Park SJ, Ostrom NP, Chen KF. Recent advances in microcavity plasma devices and arrays: A versatile photonic platform. J Phys D Appl Phys 2005;38:1644-8.
Jain KK. Nanotechnology in clinical laboratory diagnostics. Clin Chim Acta 2005;358:37-54.
Crosera M, Bovenzi M, Maina G, Adami G, Zanette C, Florio C, et al.
Nanoparticle dermal absorption and toxicity: A review of the literature. Int Arch Occup Environ Health 2009;82:1043-55.
Nel A, Xia T, Meng H, Wang X, Lin S, Ji Z, et al.
Nanomaterial toxicity testing in the 21st
century: Use of a predictive toxicological approach and high-throughput screening. Acc Chem Res 2013;46:607-21.
George S, Pokhrel S, Xia T, Gilbert B, Ji Z, Schowalter M, et al.
Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide nanoparticle through iron doping. ACS Nano 2010;4:15-29.
Mura S, Couvreur P. Nanotheranostics for personalized medicine. Adv Drug Deliv Rev 2012;64:1394-416.