412 JOURNAL OF COSMETIC SCIENCE SKIN DELIVERY METHODS OF CURCUMIN Even though curcumin has several potential applications in many fields, its targeted outcomes are limited by its low hydrophilicity, low bioactive absorption, bioavailability, rapid metabolization, low penetration, and targeted application efficacy (72). Therefore, the careful selection and improvements on the delivery mechanisms of curcumin to the targeted site of action are critical factors to get optimum benefits from curcumin products in combatting skin aging. Several delivery mechanisms including the delivery of curcumin in the form of solvent extracts, as conjugates with other molecules or structures, and using nano-carriers are discussed in this section. CURCUMIN EXTRACTS Several studies have reported that both oral and topical administration of curcumin have enhanced skin antiaging properties. One study revealed that there is a significant difference in C-reactive protein levels, an antiaging inflammatory marker, in rats treated with curcumin at doses of 100 mg, 200 mg, and 400 mg/kg of body weight (73). In addition, this study also showed that oral administration of curcumin daily for 6 months ensured the maintenance of antioxidant capacity and super oxide dismutase at a satisfactory range even in older rats (73), as curcumin exhibits favorable influence in slowing down aging by suppressing age-related changes in inflammatory indices. On the other hand, topical treatment of 2 mg/mL of curcumin in 0.5% carboxymethyl cellulose sodium was reported to exert effective photo-protective effects on UVB-induced hairless mice and immortalized HaCaTs (49). Further, treatment of human skin fibroblasts with low doses of curcumin (20 μM) in dimethyl sulfoxide showed induction of heme oxygenase-1 (HO-1), which led to a protective hormetic effect to further stress responses during cellular aging of the skin (69). Topical formulations of curcumin using hydroalcoholic extract, dry extract, and β-cyclodextrin extract prepared with other ingredients were evaluated for skin permeation and anti-inflammatory activity, where cyclodextrin encapsulation exerted better stability during skin permeation, hence revealing an effective way of using curcumin in antiaging formulations. Moreover, the formulations developed enabled limited penetration of curcumin to the superficial layers of the skin, thus permitting local use as a topical anti- inflammatory (74). CURCUMIN CONJUGATES In order to enhance the delivery efficiency of curcumin for cosmetic applications, formation of curcumin conjugates with other delivery-assisting molecules is an attractive option to overcome the challenges of low water solubility, less bioavailability, and rapid metabolization. For example, curcumin encapsulated in silk fibroin films (silk/cur), which were developed for the study of cell proliferation and regulation of markers, resulted in remarkable antiaging properties when compared to free curcumin (75). Slow release of curcumin is due to the strong binding of curcumin molecules to the beta-sheet domains of silk fibroin. In another study, curcumin encapsulated in bio glass chitosan having a number of compact and well-aligned collagen showed significant DPPH radical antioxidant scavenging activity (91%), which has a potential application for skin health (76). As skin inflammation plays

413 Curcumin Against Skin Aging an effective role in skin aging, curcumin micelles prepared with methoxy poly (ethylene glycol) and block-poly (ε-caprolactone) displayed better anti-inflammatory effects than dexamethasone ointments (77). NANO-ENCAPSULATED CURCUMIN Many research studies are focusing on the use of nanocarriers for cosmetic applications. Curcumin delivery via nanocarriers such as nanospheres, nanocapsules, nanoemulsions, etc., has been reported. Nanospheres and nanocapsules: Curcumin nanospheres have been shown to exhibit high antioxidant activities and anti-inflammatory responses (78). Lipid core nanocapsules prepared by the encapsulation of curcumin and resveratrol showed enhanced photo stability and antioxidant capacity (79). Lipid core nanocapsules can be an excellent candidate for skin treatment via codelivery of resveratrol and curcumin when applied topically. Nanoparticles and nanofilms: In another study, silk curcumin nanoparticles (silk/cur NP) have been shown to be superior to free curcumin in retarding cell aging (75). In a study conducted to evaluate dermal penetration, curcumin smart films prepared using printer paper as a matrix and ethanol (96% v/v) as the solvent showed more effective dermal and transdermal penetration of curcumin than curcumin bulk and curcumin nanosuspensions. The result suggests a new dermal penetration mechanism of curcumin for the development of antiaging topical drug products (80). Nanosomes: In a similar study, skin penetration capabilities were evaluated by using the ethanolic curcumin extract loaded to liposomes, ethosomes, and transfersomes. The efficacy of penetration was greater with the extract loaded to transfersomes than to liposomes and ethosomes. These vesicles with better skin penetration have shown improvement in skin properties like skin hydration and sebum content (81). Solid lipid nanoparticles: Curcumin-loaded solid lipid nanoparticles with an average particle size of 134.6 nm and a total drug content of 92.63% were produced using a micro-emulsification technique, where the main focus was to enhance the bioavailability of curcumin and to assess its therapeutic usefulness (82). Another study reported the encapsulation of curcumin into two biodegradable polymeric nanospheres, ethyl cellulose and methyl cellulose, prepared by dialysis. The application of these nanospheres on pig- ear skin revealed a better radical scavenging activity than curcumin. Nanoencapsulation of the light-sensitive curcumin also offers protection from photo degradation and enables curcumin to retain its antioxidant capacity (83). Microemulsions and nanoemulsions: Incorporating curcumin into a microemulsion was reported to improve the antioxidant capacity and reduce UV-induced photo damage during a study conducted using immortalized HaCaT cells (84). Curcumin-loaded coconut oil and honey nanoemulsion was prepared by varying honey (1–3%), virgin coconut oil (1.0–1.5%), and Tween 80 (Croda, Inc., Princeton, NJ, USA) (5.0–9.0%) amounts using phase inversion temperature, a low-energy emulsifying technique. This nanoemulsion was found to have high stability, but the radical scavenging activity of nanoemulsion was lower (20%) than that of free curcumin. However, the nanoemulsion appeared to increase the in vitro release rate of curcumin by about 42%, especially in improving skin permeation and kinetic release (85). A similar study conducted with the preparation of curcumin nanoemulsions