INNOVATIV E SUNFILTER FORMULATIONS AND CARRIERS FOR THE FUTURE. ENCAPSULA TION OF BI2TI2O7 NANOCOMPOSITES WITH DENDRITIC SILICON DIOXIDE MICROSPHERES (DSMS), AND ORGANIC FILTERS INCLUDING SINAPOYL MALATE (SM) AND BAICALIN (BS/BTO-DSM) TiO2 and ZnO particles have been commonly used as inorganic fi lters. Although inorganic fi lters present less skin penetration concerns than organic fi lters, the harmful photocatalytic activity that can induce ROS generation and ultimately damage to cells and DNA eventually may lead to carcinogenesis. Therefore, different surface-coating or encapsulation strategies have been adopted to overcome these challenges to obtain effective and safety inorganic fi lters with low photocatalytic activity. DSMs enca psulated with inorganic fi lter Bi2Ti2O7 nanocomposites (BTO-DSMs) and decorated with organic fi lters including SM and baicalin (BS/BTO-DSM) were rationally designed to effectively enhance UV protection while effectively scavenging the generated ROS and reducing skin permeability (the UV shielding properties were investigated in vitro by the calcein-AM/PI double-staining assay and MTT assay on HaCaT cells). To maintain the amount of active ingredients (Ti and SM) in 0.1 mg/mL, 10 mL of product should contain 22 mg of TiO2-DSM, 25 mg of BTO-DSM, 9 mg of SM/BTO-DSM, and 10 mg of BS/BTO-DSM with 10 mL of emulsion. The baica lin acted as the ROS scavenger to effi ciently eliminate the produced ROS gener- ated from the organic fi lters. The photodegradation of MO (methyl orange) was used to assess the photocatalytic activities of samples. Before the irradiation with UV light, sam- ples (7.5 mg) were added to MO (6 mL, 60 μM) aqueous solution and kept stirring for 0.5 h. Then, the mixture was irradiated with a UVB/UVA (254/365, 16 W) light for 3 h, and the sample was collected at a regular interval (0.5 h). The obtained samples were centrifuged, and the absorbance (465 nm) of solution was measured by a UV-Vis spec- trophotometer. The protect ion effects against UV irradiation on the skin of female BALB/c nude mice were further evaluated. The mice were placed under UVB/UVA (254/365 nm, 16 W) radiation for 0.5 h. Three days after UV radiation, the dorsal skin was re- moved and stained with hematoxylin/eosin (H&E) as well as Masson’s trichome for histology. Moreover, epidermal thickness and relative keratin percentage of each group were measured. To further evaluate the skin penetration in vivo, FITC (fl uorescein isothiocyanate) and FITC/BTO-DSM were applied topically onto the dorsal skin of the mice. Both the FITC and FITC/BTO-DSM samples had the same amount of FITC (0.1 mg/mL). Af- ter applying the samples for 6 h at room temperature, the skin samples were wiped topically fi ve times with PBS buffer and alcohol. After that, the dorsal skin was re- moved, sectioned into slices, mounted on glass slides, and imaged by a laser scanning confocal microscope. Thus, the r esulting BS/BTO-DSM presented excellent in vitro anti-UV performance and in vivo UV protection against keratinocyte apoptosis and epidermal hyperplasia without long-term toxicity. The introduction of SM into BTODSM signifi cantly broadened the UV shield range, which also prevented the SM direct contact with the epidermis and penetration behaviors (73). DISTRIBUTION OF UV FILTERS ON THE SKIN 313

NON-PENETRA TING SUNSCREENS (NPSUNS) A form of s unscreens, the skin NPSUNs, could be used in cosmetics and pharmaceuti- cal personal care products. The main reason that led to the design of the new photopro- tectors was the immobilization of UV-absorbing moieties contained in the chemical backbone of Jojoba oil. Thus, several forms of fi lters were created that included conju- gates of Jojoba oil with UV sunscreen molecules. Jojoba oil consists of esters of fatty acids (C18–C22) with fatty alcohols (C18–C22) and has a wax structure. Its use is rather common in cosmetics and pharmaceutical products. NPSUNs have physico- chemical characteristics, which allow these derivatives to stay on the upper SC, where sunscreen molecules are activated, and, thus, no further penetration to the inner dermal strata or into the systemic circulation is feasible. It was found that OMC-NPSUN pos- sesses a similar UV absorption spectrum as OMC and could be easily formulated in cosmetic and pharmaceutical topical products. No permeation of OMC-NPSUN across the skin was observed in 24-h in vitro permeation experiments after application of ei- ther neat substances or OMC-NPSUNs formulated in oil-in-water cream, in water-in- oil cream, or in Jojoba oil (74). LIPID CARRI ERS Lipid carri ers seem to be a good alternative to formulate chemical UV fi lters reducing their skin penetration while maintaining good photo-protective abilities. Gilbert et al. compared percutaneous absorption and cutaneous bioavailability of BP-3 (concentration 5% w/w) loaded into SLNs, nanostructured lipid carriers (NLCs), nanostructured poly- meric lipid carriers (NPLCs), and NCs. The NLCs ar e considered as the second generation of SLNs that allow a) more effective drug loading, b) an adjustment of the drug distribution profi le, and c) an extended drug entrapment during storage. NCs and NPLCs have a characteristic hydrophobic polymer around their lipid core (Figure 2). This polymeric lipid layer of NCs allows lipophilic compounds to be released and protects the encapsulated molecules from photodegradation. A penetrati on and permeation study was carried out, on porcine ear skin, according to OECD TG 428 guideline (2004). Static Franz diffusion cells were used to evaluate the percutaneous permeation of BP-3 from the developed suspensions. Porcine skin was mounted between donor and receptor compartments. Donor media were composed of 1 mL of the tested formulations containing 5% of BP-3 to ensure BP-3 infi nite dose conditions. Every hour for the six fi rst hours, and then, 22, 23, and 24 h after formulations were applied into Franz cell donor compartment, an aliquot of 500 μL of receptor medium was withdrawn and immediately replaced with an equal volume of freshly prepared one. BP-3 skin dis- tribution study was carried out 24 h after the permeation experiment. Skin samples were removed from Franz diffusion cells and cleaned with a swab that was previously moistened into distilled water. SC was entirely removed applying 20 successive tape stripping (TS) at the skin surface. Samples were analyzed using high-performance liquid chromatography. Results show ed that BP-3 partition coeffi cient between the SC and SLN suspension did not signifi cantly differ from that obtained with the BP-3 albumin aqueous solution (AAS). Compared to SLNs and AAS, BP-3 showed a better affi nity for NLC, NPLC, and NC suspensions, and once BP-3 crosses the SC barrier, it showed a higher tendency to penetrate the epidermis compartment. NLCs did not permit to maintain BP-3 into the SC because JOURNAL OF COSMETIC SCIENCE 314