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PEER-REVIEW | COSMECEUTICALS | action in the target cell or tissue in human


skin; and finally, are there published, peer- reviewed, double-blind, placebo-controlled, statistically significant, clinical trials to substantiate the efficacy claims? However, since cosmeceuticals remain an unrecognised category by the US Food and Drug Administration (FDA) stringent regulatory pathways do not exist to guide research and marketing. Efforts have only recently been initiated to address the issues surrounding quality control and to establish industry standards, since cosmeceuticals intend to deliver on a higher level than cosmetics that simply colour and scent the skin, and should be clinically tested for efficacy not only to insure a proven skin


skin ageing process has enabled manufacturers to design cosmeceuticals with active ingredients that mitigate or reverse the mechanisms of skin ageing.


benefit but also to substantiate marketing claims3


. There is limited


research being done on cosmeceuticals in academic dermatology, and there have been no NIH grants available for cosmeceutical research to date. As a result, the best research comes from industry- sponsored studies, which may lead to the development of inherent biases. Cosmeceuticals are developed in


formulations around an active ingredient that is thought to have a functional benefit to skin health. Once a possible functional cosmeceutical active ingredient has been identified, it is synthesized and typically applied to a fibroblast cell culture to identify the key skin mediators that are modulated. The ingredient is usually tested in a rodent model


for elucidation of


further its


mechanism of action and to confirm the desired skin benefits. After the active ingredient is placed in a vehicle suitable for human application clinical studies are undertaken, and successful human clinical


14 ❚


NouriCel- MD


NouriCel -MD


PSP


Neocutis SCA


14 –


60 + 12


Table 1 ASPS evidence rating scale for therapeutic studies


Rating Description I


II III


IV V


High quality, multi/single centered, randomised controlled trials with adequate power; systematic review of these studies (minimum 100 study subjects)


Lesser quality randomized controlled trial; prospective cohort or comparative study


Retrospective cohort/comparative study; case-control study


Cases series with pre/post-test; only post-test


Expert opinion; case report; evidence based on bench research, physiology


Deeper understanding of the


studies pave the way for introduction into the marketplace via ingredient licensing arrangements. The applications of cosmeceuticals are


broad and include improving skin radiance and texture, acne reduction, and decreasing pigmentation. However, they are most well-known for combating the effects of ageing. In fact, deeper understanding of the skin ageing process has enabled manufacturers to design cosmeceuticals with active ingredients that mitigate or reverse the mechanisms of skin ageing. Both intrinsic and extrinsic ageing, the former largely determined by genetics and the latter by environmental factors such as UV exposure and lifestyle, result in reduction of skin collagen and


elasticity, dermis thinning, heterogeneous pigmentation, and wrinkling4


. This article will


focus on the clinical evidence available regarding the efficacy and safety of common active ingredients of cosmeceuticals including growth factors, peptides, stem cells, antioxidants and pigment/ erythema reducing agents. The American Society of Plastic Surgeons rating scale of therapeutic studies was utilized to assign the relevant level of evidence (Table 1).


Growth factors


Growth factors (GF’s) comprise a large group of regulatory proteins that attach to cell surface receptors and mediate inter- and intracellular signalling pathways that control fibroblast and keratinocyte proliferation within the dermis, thus inducing extracellular matrix (ECM)


formation5


Table 2 Overview of clinical studies with topical growth factors


. Studies have shown minimal penetration of intact stratum corneum by hydrophilic molecules that have a molecular weight greater than 0.5 KDa6


, and


Photodamage Topical 60 days Photodamage Topical 3-6


months – Periorbital,


perioral wrinkles


25 + Periocular rhytides


78.6% Significant


56/LOE-III 57/LOE-II


Topical 6 months 33 and 25% 58/LOE-III Topical 14 weeks Significant


in periocular rhytides and skin texture


March 2015 | prime-journal.com 59/LOE-II


GFs are large, hydrophilic molecules with a molecular weight of over 15 KDa. However it is proposed that topical absorption occurs by way of hair follicles, sweat


compromised skin 7, 8


glands, and . In


regards to their functionality outside their physiologic environment, it was shown they can retain stability for over 24 months9


. FDA investigation into the


Growth factors


Patients


Placebo controlled Study


endpoints


Route of administration Treatment


Results/ improvement


Reference/ level of evidence


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