Beruflich Dokumente
Kultur Dokumente
1
Department of Dermatology, Uniformed Services University of the Health
Sciences, Bethesda, MD, USA
2
Center for Prostate Disease Research, Department of Surgery, Uniformed
Services University of the Health Sciences, Bethesda, MD, USA
3
Department of Pathology, Uniformed Services University of the Health
Sciences, Bethesda, MD, USA
Abstract
Curcumin, an active constituent of the spice turmeric, is well the chemopreventive potential of curcumin in various skin
known for its chemopreventive properties and is found to be diseases like psoriasis, vitiligo, and melanoma is discussed.
beneficial in treating various disorders including skin dis- The application of curcumin in skin regeneration and wound
eases. Curcumin protects skin by quenching free radicals healing is also elucidated. We also explored the recent inno-
and reducing inflammation through the inhibition of nuclear vations and advances involved in the development of trans-
factor-kappa B. Curcumin also affects other signaling path- dermal delivery systems to enhance the bioavailability of
ways including transforming growth factor-b and mitogen- curcumin, particularly in the skin. Recent clinical trials per-
activated protein kinase pathway. Curcumin also modulates taining to the use of curumin in skin diseases establishes its
the phase II detoxification enzymes which are crucial in benefits and also the need for additional clinical trials in
detoxification reactions and for protection against oxidative other diseases are discussed. V C 2013 BioFactors, 39(1):141–
BioFactors 141
BioFactors
pharmacologic agents to inhibit or reverse the development of developed [65]. Some adjuvants that may block metabolic
cancer. Curcumin is known for its chemopreventive and anti- pathways of curcumin are also being used to improve the bioa-
carcinogenic activity. It has been shown to induce autophagy vailability of curcumin. Other promising formulations such as
along with apoptosis in the treatment of melanoma, which liposomes, micelles, nanoparticles, and phospholipid com-
provides a nontoxic option for combinatorial chemotherapy plexes, which provide longer circulation, better permeability,
with significant potential [61]. and resistance to metabolic processes are also being used [1].
NF-jB has been reported to play a central role in cell sur- In vitro skin penetration study showed that curcumin- soy-
vival and growth in many types of cancer including melanoma. bean phospholipids-loaded liposomes can significantly endorse
Curcumin has been shown to inhibit NF-jB activity in several drug permeation and deposition and also inhibited the growth
cell types and selectively inhibit the growth of melanoma cells, of melanoma cells to a greater extent. These results suggest
but not normal melanocytes [62]. Curcumin induced apoptosis that curcumin-soybean phospholipids-loaded liposomes may
and inhibit NF-kappa B-driven reporter activity with decreased act as a transdermal carrier for curcumin in cancer treatment
levels of phospho-I jB a, and also decreased expression of NF- [66]. Earlier, Wang et al. developed doxorubicin (DOX)-loaded
jB-target genes like COX-2 and cyclin D1 in melanoma cells. long circulating liposomes combined with curcumin (CUR)
Curcumin also inhibited skin squamous cell carcinoma growth (DOX-CUR-LCLs), as a novel formulation for cancer treatment.
and blocks tumor progression by inhibiting mTOR signaling. Cytotoxicity evaluation showed that DOX-CUR-LCLs had a sig-
Dibenzoylmethane, a b-diketone structural analogue of curcu- nificantly higher antitumor activity than other DOX prepara-
min, has also been reported to exhibit antitumorigenic and tions. These observations suggest that this novel DOX-CUR-
chemopreventive activities [63]. It has also been shown that LCLs, combination of DOX and CUR administered in long-cir-
curcumin inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)- culating liposomes, could possibly improve antitumor activity
induced tumor promotion and TPA-responsive markers in [67].
mouse skin [64]. The protein kinase C (PKC), the major cellular Recently, a new magnetic-based core-shell particles
receptor of TPA, mediates TPA-induced biological responses in (MBCSPs) were also developed to target skin cancer cells to
mouse skin and curcumin modulates transmembrane signal deliver chemotherapeutic drugs in a controlled way. These
transduction via PKC to affect TPA-induced biochemical and particles are made up of a thermo-responsive shell of poly (N-
molecular alterations in mouse skin. isopropylacrylamide-acrylamide-allylamine) and a core of pol-
Photocarcinogenesis is caused by DNA damage to the skin y(lactic-co-glycolic acid) (PLGA) embedded with magnetite
from solar radiation in the ultraviolet range and resulting in nanoparticles. These shell particles have unique multifunc-
the development of both melanoma and nonmelanoma skin tional and controlled drug delivery characteristics with an
cancers. Curcumin has been shown to protect against the dele- ability to provide dual drug release mechanisms (a sustained
terious effects of injury by attenuating oxidative stress and release of drugs through degradation of PLGA core and a con-
suppressing inflammation [64]. Curcumin block multiple tar- trolled release in response to changes in temperature via ther-
gets of these pathways and can be used in the chemopreven- moresponsive polymer shell), and dual targeting mechanisms
tion of photoaging skin and photocarcinogenesis. Curcumin not (magnetic localization and receptor-mediated targeting) [68].
only activates caspase-3 and caspase-8 in human melanoma In vitro studies demonstrated a sustained release of curcumin
cell lines, it also induces activation of a death receptor path- from the core and a temperature-dependent release of doxoru-
way, by inducing Fas receptor [64]. bicin from the shell of MBCSPs were observed with no cytotox-
icity to normal fibroblasts [68]. MBCSPs has a great potential
as a platform technology to target, treat and monitor mela-
noma for targeted drug delivery and to reduce the side effects
5. Development of Transdermal of chemotherapeutic reagents [68].
Delivery Systems to Enhance As an alternative to traditional gels for the topical applica-
Bioavailability of Curcumin tions of hydrophobic drugs, Koop et al. demonstrated that the
xanthan-galactomannan (X:G) hydrogels system with addition
Curcumin is one of the most health beneficial components of of curcumin in microemulsion, exhibited a significantly higher
turmeric. One of the biggest challenges to use curcumin as a elastic response. In vitro skin permeation tests showed a more
therapeutic and nutritional supplement effectively is the poor pronounced lag time and more efficient permeation with their
solubility, bioavailability, and photostability of curcumin in its novel delivery system [69]. Similarly, curcumin loaded chitin
raw form. Studies to date have shown the reduced bioavaila- nanogels (CCNGs) were developed, using biocompatible and
bility of curcumin within the body is due to high intrinsic activ- biodegradable chitin. Both chitin and curcumin are insoluble
ity, poor absorption, rapid metabolism, inactivity of metabolic in water but CCNGs developed by Mangalathillam et al. form a
products, and/or rapid elimination and clearance from the very good and stable dispersion in water and their study sug-
body [1]. To overcome these limitations, efficacious formula- gested that the formulated CCNGs have specific advantage for
tions of curcumin, including nanocrystal solid dispersion, the treatment of melanoma, the most common and serious
amorphous solid dispersion, and nanoemulsion, are being type of skin cancer, by effective transdermal penetration [70].
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