4/21/2019 Nanotechnology in medicine and relevance to dermatology: Present concepts :[PAUTHORS], Indian Journal of Dermatology

REVIEW ARTICLE
Year : 2012 | Volume : 57 | Issue : 3 | Page : 169--174

Nanotechnology in medicine and relevance to dermatology: Present

concepts
KH Basavaraj
Department of Dermatology, Venereology and Leprosy, JSS Medical College, JSS University, Mysore, Karnataka, India

Correspondence Address:
K H Basavaraj
Banu, A-27, K-Block, Adichunchanagiri Road, Kuvempunagar, Mysore - 570 023, Karnataka
India

Abstract
Nanotechnology and nanomedicine are complementary disciplines aimed at the betterment of human
life. Nanotechnology is an emerging branch of science for designing tools and devices of size 1-100 nm,
with unique functions at the cellular, atomic and molecular levels. The concept of using nanotechnology
in medical research and clinical practice is known as nanomedicine. Today, nanotechnology and
nanoscience approaches to particle design and formulations are beginning to expand the market for
many drugs and forming the basis for a highly profitable niche within the industry, but some predicted
benefits are hyped. Under many conditions, dermal penetration of nanoparticles may be limited for
consumer products such as sunscreens, although additional studies are needed on potential
photooxidation products, experimental methods and the effect of skin condition on penetration. Today,
zinc oxide and titanium dioxide nanoparticles (20-30 nm) are widely used in several topical skin care
products such as sunscreens. Thus, in the present scenario, nanotechnology is spreading its wings to
address the key problems in the field of medicine. The benefits of nanoparticles have been shown in
several scientific fields, but very little is known about their potential to penetrate the skin. Hence, this
review discusses in detail the applications of nanotechnology in medicine with more emphasis on the
dermatologic aspects.

How to cite this article:

Basavaraj K H. Nanotechnology in medicine and relevance to dermatology: Present concepts.Indian J Dermatol
2012;57:169-174

How to cite this URL:

Basavaraj K H. Nanotechnology in medicine and relevance to dermatology: Present concepts. Indian J
Dermatol [serial online] 2012 [cited 2019 Apr 21 ];57:169-174
Available from: http://www.e-ijd.org/text.asp?2012/57/3/169/96186

Full Text

Introduction

Nanotechnology is the creation of functional materials, devices and systems through control of matter
on the nanometer length scale and exploitation of novel phenomena and properties (physical, chemical,
biological, mechanical, electrical) at that length scale. In the area of cosmetics and anti-aging, in
particular, as well as in the pharmaceutical arena, nanotechnology has played an important role in
delivering active ingredients to the skin, in both patch delivery and timed release application.
Nanoparticles/nanospheres sound like futuristic technology [1] The application of nanotechnology
concepts to medicine joins two large-scale cross-disciplinary fields with an unprecedented societal and
economical potential arising from the natural combination of specific achievements in the respective
fields. [2] As the need for the development of new medicines is pressing and given the inherent
nanoscale functions of the biological components of living cells, nanotechnology has been applied to
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diverse medical fields such as oncology and cardiovascular medicine. Indeed, nanotechnology is being
used to refine discovery of biomarkers, molecular diagnostics, drug discovery and drug delivery which
could be applicable to management of these patients. To achieve these aims, nanotechnology strives to
develop and combine new materials by precisely engineering atoms and molecules to yield new
molecular assemblies on the scale of individual cells, organelles or even smaller components, providing
a personalized medicine. [3],[4] Because of increased use of nanotechnology, the risk associated with
exposure to nanoparticles, the routes of entry and the molecular mechanisms of any cytotoxicity need
to be well understood. In fact, these tiny particles are able to enter the body through the skin, lungs or
intestinal tract, depositing in several organs and may cause adverse biological reactions by modifying
the physiochemical properties of living matter at the nanolevel. [5],[6],[7] Nanotechnology is being
applied to biomarker-based proteomics and genomics technologies. Nanoparticles can be used for
qualitative or quantitative in vivo or ex vivo diagnosis by concentrating, amplifying and protecting a
biomarker from degradation, in order to provide more sensitive analysis. [8] Nanoparticles are currently
being tested for molecular imaging to achieve a more precise diagnosis with high-quality images. In
fact, contrast agents have been loaded onto nanoparticles for tumor and atherosclerosis diagnosis.
Different nanoparticles have been used for molecular imaging with magnetic resonance images (MRI),
ultrasound, fluorescence, nuclear, and computed tomography imaging. [9] Nanotechnology is being
applied extensively to provide targeted drug therapy, diagnostics, tissue regeneration, cell culture,
biosensors and other tools in the field of molecular biology. Various nanotechnology platforms like
fullerenes, nanotubes, quantum dots, nanopores, dendrimers, liposomes, magnetic nanoprobes and
radio-controlled nanoparticles are being developed.

Nanomedicine

Nanomedicine is the use of nanotechnology to achieve innovative medical breakthroughs.

Nanomedicine, with its broad range of ideas, hypotheses, concepts, and undeveloped clinical devices, is
still in its early stage. This article outlines the present developments and future prospects for the use of
nanotechnology techniques in experimental in vivo and in vitro studies and in engineering nanodevices
and biosensors for clinical and investigative use in diagnosis and therapy in the fields of genetics,
oncology, cardiology, dermatology and also in the field of medicine, in general, and molecular biology, in
particular. [10] The early genesis of the concept of nanomedicine sprang from the visionary idea that
tiny nanorobots and related machines could be designed, manufactured, and introduced into the human
body to perform cellular repairs at the molecular level. Nanomedicine today has branched out in
hundreds of different directions, each of them embodying the key insight that the ability to structure
materials and devices at the molecular scale can bring enormous immediate benefits in the research
and practice of medicine. [11] Nanomedicine is the application of nanotechnologies in medicine for
maintenance and improvement of human life using the knowledge on human organism at a molecular
level [Figure 1]. Application of nanoparticles and nanomaterials for the diagnostic and therapeutic
purposes is now significantly extended in nanomedicine. [12] Nanomedicine involves utilization of
nanotechnology for the benefit of human health and well-being. The use of nanotechnology in various
sectors of therapeutics has revolutionized the field of medicine where nanoparticles of dimensions
ranging between 1 and 100 nm are designed and used for diagnostics, therapeutics and as biomedical
tools for research. [13]{Figure 1}

Nanotechnology in Dermatology

Today, cosmetic formulation contains nano-sized structures.Nanoemulsions are commonly used in

certain cosmetic products such as conditioners or lotions. [14] Many modern cosmetic or sunscreen
products contain nano-sized components [Figure 2]. Nanoemulsions are transparent and have unique
tactile and texture properties; nanocapsule, nanosome, noisome, or liposome formulations contain
small vesicles (range: 50-5000 nm) consisting of traditional cosmetic materials that protect light- or
oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic research suggests that
vesicle materials may penetrate the stratum corneum (SC) of the human skin, but not into living skin.
Modern sunscreens contain insoluble titanium dioxide (TiO 2 ) or zinc oxide (ZnO) nanoparticles (NP),
which are colorless and reflect/scatter ultraviolet (UV) more efficiently than larger particles. Also,
nanomaterials such as nano-sized vesicles or TiO 2 and ZnO nanoparticles which are currently used in
cosmetic preparations or sunscreens pose no risk to human skin or human health, although other NP
may have properties that warrant safety evaluation on a case-by-case basis before human use. [15]
The first generation of lipid nanoparticles was introduced as solid lipid nanoparticles (SLN) and the
second, improved generation as nanostructured lipid carriers (NLC). Identical to the liposomes, the lipid

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nanoparticles appeared as products first on the cosmetic market. The cosmetic benefits of lipid
nanoparticles include enhancement of chemical stability of actives, film formation, controlled occlusion,
skin hydration, enhanced skin bioavailability and physical stability of the lipid nanoparticles as topical
formulations. NLC are on the market as concentrates to be used as cosmetic excipients, special
formulation challenges for these products and they also appeared in a number of finished cosmetic
products worldwide. [16]{Figure 2}

Due to the lower risk of systemic side effects, topical treatment of skin disease appears favorable, yet
the SC counteracts the penetration of xenobiotics into viable skin. Particulate carrier systems may
mean an option to improve dermal penetration. Since epidermal lipids are found in high amounts within
the penetration barrier, lipid carriers attaching themselves to the skin surface and allowing lipid
exchange between the outermost layers of the SC and the carrier appear promising. Besides liposomes,
SLN and NLC have been studied intensively. [17] Today, SLN and NLC exhibit many features for dermal
application of cosmetics and pharmaceutics, i.e. controlled release of actives, drug targeting, occlusion
and penetration enhancement and also increase of skin hydration associated with it [Figure 3]. [18] The
potential of topically applied NP to penetrate human skin and produce a systemic health risk has been
suggested in reviews by Hoet et al. [19]{Figure 3}

With advances in nanotechnology, pure silver has been recently engineered into nanometer-sized
particles (diameter <100 nm) for use in the treatment of wounds. In conjunction with other studies, it
was demonstrated that the topical application of silver nanoparticles (AgNPs) can promote wound
healing through the modulation of cytokines. Nonetheless, the question as to whether AgNPs can affect
various skin cell types - keratinocytes and fibroblasts - during the wound-healing process still remains.
[20] A study was conducted for evaluating in vitro skin penetration of AgNPs and the results showed
that AgNPs' absorption through intact and damaged skin was very low but detectable, and that in case
of damaged skin it was possible to increase permeation of silver when applied as nanoparticles.
Moreover, AgNPs could be detected in the SC and the outermost surface of the epidermis by electron
microscopy, and silver applied as nanoparticles coated with polyvinylpirrolidone is able to permeate the
damaged skin in an in vitro diffusion cell system. [21] The topical administration of the lyotropic liquid
crystal nanocube to SC rapidly broke down the lipid lamella structure which would be recognized as a
wound without organ change and the observations suggested that a structural change in lipid can
stimulate and trigger recognition of a slight injury in the wound defense and a repair response as
homeostasis and this actually succeeded in improving photo-induced hyperpigmentation on human
face. [22]

Skin can be exposed to solid nanoscale particles through either intentional or non-intentional means.
Intentional dermal exposure to nanoscale materials may include the application of lotions or creams
containing nanoscale TiO 2 or ZnO as a sunscreen component or fibrous materials coated with
nanoscale substances for water- or stain-repellent properties. Non-intentional exposure could involve
dermal contact with anthropomorphic substances generated during nanomaterial manufacture or
combustion. [23] Tinkle et al. provided compelling evidence that nanoparticles could penetrate the skin
in demonstrating epidermal and dermal penetration by fluorescent microspheres (0.5-1.0 μm) in human
skin in an in vitro flexed skin model. [23]

Dermal Exposure to Nanoparticles

The interaction of nanoparticles with skin has received significant attention recently because of the
increasing use of nanoscale particles in stain-resistant clothing, cosmetics, and sunscreens. The dermal
route of exposure is also important because of the tendency of agglomerated airborne nanoparticles to
settle on surfaces and the difficulties in preventing dermal contact with these settled particles. Several
studies have been conducted examining the ability of nanoscale TiO 2 , used as an ultraviolet (UV)-
absorbing component in sunscreens, to penetrate the epidermis in human volunteers and animal and in
vitro models. [24],[25],[26],[27],[28] The primary TiO2 particles used in these studies ranged in size
from 10 to 60 nm, with larger-sized aggregates present. In all of these studies, nanoparticles did not
appear to penetrate past the SC of the epidermis, though in some cases, accumulation in the hair
follicles was observed. [7] Studies have found 20-nm, negatively charged polystyrene spheres to
behave similarly to nanoscale TiO 2 with regard to their follicular localization and lack of SC
penetration. [29]

In contrast to the studies of nanoscale TiO 2 and polystyrene, a study examining the dermal
penetration of quantum dots has shown limited dermal penetration. [30] This study [30] utilized
scanning fluorescent confocal microscopy to examine the influence of size, shape and surface charge on
quantum dot penetration in an in vitro, flow-through diffusion porcine skin model. A small fraction of
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the applied dose for some quantum dot species was shown to penetrate the SC, with an even smaller
fraction escaping the epidermis and accumulating within the dermis. This penetration was dependent
upon size, shape and surface charge of the quantum dots, with smaller, spherical particles
demonstrating greater penetration than larger, ellipsoidal particles. None of the quantum dot species
were shown to pass through the entire skin thickness to the opposing perfusate side of the diffusion
cell. This limited dermal penetration has also been shown recently for <10-nm maghemite and iron
nanoparticles using an in vitro human skin model, [31] suggesting that "smaller" nanoparticles may
have this ability. Though studies have yet to examine the effect of skin condition on nanoparticle
absorption, damaged skin would be expected to provide less of a barrier, and this issue may be
important in certain situations such as the application of nanoparticle-containing sunscreens to sun-
damaged skin. In support of this idea, the flexing of skin in vitro has been shown to increase dermal
penetration of micron-sized dextran particles and derivatized fullerenes. [23],[32] Together, the
available data suggest that healthy, intact skin is a significant barrier to certain nanomaterials.

Conclusion

Nanotechnology is a fast-expanding area of science. This area of research is anticipated to lead to the
development of novel, sophisticated, multifunctional applications which can recognize cancer cells,
deliver drugs to target tissue, aid in reporting outcome of therapy, provide real-time assessment of
therapeutic and surgical efficacy, and most importantly, monitor intracellular changes to help prevent
precancerous cells from becoming malignant. Although the expectations from nanotechnology in
medicine are high and the potential benefits are endlessly enlisted, the safety of nanomedicine is not
yet fully defined. Use of nanotechnology in medical therapeutics needs adequate evaluation of its risk
and safety factors. However, it is possible that nanomedicine in future would play a crucial role in
treatment of human diseases and also in enhancement of normal human physiology. With concurrent
application of nanotechnology in other fields, its utility is likely to extend further into diagnostics,
molecular research techniques and tools.

Future of Nanotechnology

Nanotechnology has a bright future with multiple applications in many areas including engineering,
optics, energy, and consumer products. Nanomedicine will develop applications for novel and superior
diagnostic, therapeutic and preventive measures. Exciting achievements based on nanotechnology and
nanomedicine await us in the future. Yet, there are as many challenges to get it right, and recognize
and avoid potential risks associated with these new developments. Essential for the successful present
and future development is a multidisciplinary team approach involving material scientists, physicians
and toxicologists who work closely together.

We will also need to push the existing knowledge as far as it will go in the service of protecting people.
Where existing knowledge fails, new research is needed to fill the gaps. This must be administered
strategically and targeted to addressing specific issues in a timely manner. Failing to take these steps
will ultimately lead to people's health being endangered and emerging nanotechnologies floundering.
But with foresight, sound science and strategic research, we have the opportunity to ensure that
emerging nanotechnologies are as safe as possible, while reaching their full potential.

Ongoing efforts by scientists, researchers, and medical personnel can sincerely ensure to "do big things
using the very small." But as such, the applications of nanotechnology in dermatology are still a
developing and challenging field to dermatologists.

Future of Nanomedicine

Nanotechnology is beginning to change the scale and methods of vascular imaging and drug delivery.
Indeed, the National Institutes of Health (NIH) Roadmap's "Nanomedicine Initiatives" envisage that
nanoscale technologies will begin yielding more medical benefits within the next 10 years. This includes
the development of nanoscale laboratory-based diagnostic and drug discovery platform devices such as
nanoscale cantilevers for chemical force microscopes, microchip devices, nanopore sequencing, etc. The
National Cancer Institute has related programs too, with the goal of producing nanometer scale
multifunctional entities that can diagnose and deliver therapeutic agents and monitor cancer treatment
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progress. These include design and engineering of targeted contrast agents that improve the resolution
of cancer cells to the single cell level and nanodevices capable of addressing the biological and
evolutionary diversity of the multiple cancer cells that make up a tumor within an individual. Thus, for
the full in vivo potential of nanotechnology in targeted imaging and drug delivery to be realized,
nanocarriers have to get smarter. Pertinent to realizing this promise is a clear understanding of both
physicochemical and physiological processes. These form the basis of complex interactions inherent to
the fingerprint of a nanovehicle and its microenvironment, the examples of which include carrier
stability, extracellular and intracellular drug release rates in different pathologies, interaction with
biological milieu, such as opsonization and other barriers en route to the target site, be it anatomical,
physiological, immunological or biochemical, and exploitation of opportunities offered by disease states
(e.g. tissue-specific receptor expression and escape routes from the vasculature). Inherently, carrier
design and targeting strategies may vary in relation to the type, developmental stage, and location of
the disease. Toxicity issues are of particular concern but are often ignored. Therefore, it is essential that
fundamental research be carried out to address these issues if successful efficient application of these
technologies has to be achieved. The future of nanomedicine will depend on rational design of
nanotechnology materials and tools based on a detailed and thorough understanding of biological
processes rather than forcing applications for some materials currently in vogue.

Acknowledgement

Dr. K H Basavaraj thanks Professor Suresh, Vice Chancellor, JSS University. Mysore, India, and the
Principal, JSS Medical College, India, for their support and encouragement.

Multiple Choice Questions

Nanotechnology is an emerging branch of science for designing tools and devices of size:

1-100 mm1-100 nm1-100 cm1-100 mNanotechnology is the creation of:

Functional materialsControl on the nanometer length scale

Exploitation of propertiesAll of the aboveTiny particles enter the body through:

SkinLungs or intestinal tracta and b

EyesNanotechnology is being applied extensively to provide targeted:

Drug therapyDiagnosticsTissue degenerationAll of the aboveEarly genesis of the concept of

nanomedicine sprang from the visionary idea:

EndoscopeNanorobots and related machinesMagnetic resonance imagesGenetic

engineeringNanoparticles are:

TransparentOpaqueTurbidGreasyStratum corneum counteracts the penetration of:

AntibioticsXenobioticsDeodorantsConditionersSilver nanoparticles can promote wound healing through

the modulation of:LymphocytesLeukocytesPlateletsCytokinesIncreasing use of nanoscale particles in:

Stain resistant clothingCosmeticsSunscreensAll of the aboveScientists, researchers and medical

personnel can sincerely ensure to do:

Small things using the very bigBig things using the very smallBoth of the aboveNone of the above

Answers:

1. b

2. d

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3. c

4. d

5. b

6. a

7. b

8. d

9. d

10. b

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