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. 2015 Dec;14(12):1278-85.
doi: 10.1038/nmat4422. Epub 2015 Sep 28.

A sunblock based on bioadhesive nanoparticles

Yang Deng  1 , Asiri Ediriwickrema  1 , Fan Yang  1 , Julia Lewis  2 , Michael Girardi  2 , W Mark Saltzman  1
Affiliations

A sunblock based on bioadhesive nanoparticles

Yang Deng et al. Nat Mater. 2015 Dec.

Abstract

The majority of commercial sunblock preparations use organic or inorganic ultraviolet (UV) filters. Despite protecting against cutaneous phototoxicity, direct cellular exposure to UV filters has raised a variety of health concerns. Here, we show that the encapsulation of padimate O (PO)--a model UV filter--in bioadhesive nanoparticles (BNPs) prevents epidermal cellular exposure to UV filters while enhancing UV protection. BNPs are readily suspended in water, facilitate adherence to the stratum corneum without subsequent intra-epidermal or follicular penetration, and their interaction with skin is water resistant yet the particles can be removed via active towel drying. Although the sunblock based on BNPs contained less than 5 wt% of the UV-filter concentration found in commercial standards, the anti-UV effect was comparable when tested in two murine models. Moreover, the BNP-based sunblock significantly reduced double-stranded DNA breaks when compared with a commercial sunscreen formulation.

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Figures

Figure 1
Figure 1. Comparison of BNP based sunscreen to commercial sunscreen
(A) Sunscreen formulations are applied onto the skin. (B) After application, commercial sunscreen penetrates into the skin whereas the BNP formulation remains on the stratum corneum. (C) After sunlight exposure, UV filters produce deleterious ROS which can damage adjacent tissue, however, BNPs do not penetrate into the skin and prevent ROS mediated toxicity by confining these toxic products within the particle. BNP - bioadhesive nanoparticle, ROS - reactive oxygen species, UV – ultraviolet.
Figure 2
Figure 2. Evaluation of BNP adhesion
(A) Surface aldehyde concentration on nanoparticles were recorded as a function of incubation time with NaIO4. Data are shown as mean ± SD (n = 4). (B) Surface immobilization of BNPs on lysine coated slides. The surface density of aldehydes was controlled by incubation time with NaIO4. The non-treated group (0 min) represent NNPs (non-adhesive control). Data are shown as mean ± SD (n = 4). (C) BNPs and NNPs at 1 mg/ml were incubated on pig skin for six hours in a humidity chamber at 32°C. The scale bar represents 200 µm. (D) The fluorescence was quantified and normalized to the average fluorescence of BNPs. Data are shown as mean ± SD (n = 10), ****P < 0.0001 (student t-test). (E) BNPs encapsulating an infrared dye, IR-780, were applied on dorsal skin of mice and BNP skin retention was imaged with Xenogen at different time points. (F) The fluorescence was quantified and normalized to the fluorescence intensity at time zero. (G) BNPs encapsulating an infrared dye, IR-780, were applied to the dorsal skin of mice. After wiping with a wet towel (T) or washing with water (W), BNP skin retention was imaged with Xenogen. (H) The fluorescence after wiping or washing was quantified and normalized to the fluorescence intensity at time zero. BNP - bioadhesive nanoparticle, NNP - non-bioadhesive nanoparticles.
Figure 3
Figure 3. Synthesis and in vitro evaluation of PO/BNPs
(A) TEM image of PO/BNPs. The scale bar is 200 nm. (B) PO retention within PO/BNPs in artificial human sweat at 32°C and 37°C. Data are shown as mean ± SD (n = 4). (C) Absorbance efficiency of PO/BNPs, PO emulsion in water (PO/water), PO dissolved in mineral oil (PO/Oil), PO dissolved in DMSO (PO/DMSO) at a PO concentration of 0.01 mg/ml, and sunscreen dissolved in mineral oil (Sunscreen/Oil) at 0.01 mg/ml of active ingredients. UV filters within their vehicles were scanned for UV absorbance between 260–400nm. The data are plotted with background subtraction of blank vehicles. Data are shown as mean (n=4). (D) ROS formation as measured by DHR fluorescence after UV irradiation. DHR was incubated with PO/BNPs, blank BNPs, PO emulsion and PBS control. Data are shown as mean ± SD (n = 8), ****P<0.0001. BNP - bioadhesive nanoparticle, DHR – Dihydrorhodamine, DMSO - dimethyl sulfoxide, PO – padimate O, ROS – reactive oxygen species, TEM - transmission electron microscopy, UV – ultraviolet.
Figure 4
Figure 4. Histology of dorsal mouse skin sections receiving different topical interventions three days after high dose UV (2160 J/m2)
Topical interventions included (A–B) normal skin without UV exposure, (C–D) sunscreen, (E–F) PO/BNPs, (G–H) blank BNPs, (I–J) no protection. There was significant acanthosis (double arrow) with prominent rete ridges (arrow) and orthokeratosis (*) present in the unprotected samples, consistent with epidermal hypertrophy. Skin protected by sunscreen showed thickened orthokeratosis as well relative to the skin protected by PO/BNPs and the normal skin control. (K) Epidermal thickness and (L) percent area of keratin within the dorsal skin after receiving topical interventions and UV irradiation. The scale bar represents 100 µm. Hematoxylin and eosin staining (A, C, E, G, I). Trichrome staining (B, D, F, H, J). *p<0.05 compared to all other treatment groups. BNP - bioadhesive nanoparticle, PO – padimate O.
Figure 5
Figure 5. CPD staining of mouse dorsal epidermal sheets after receiving different topical interventions and UVB irradiation (160 J/m2)
Epidermal sheets were prepared one hour after exposure to UVB (A). The fluorescence of CPD on skin receiving different topical interventions was quantified (B). The scale bar represents 50 µm. Data are shown as mean ± SD (n=3), **p<0.01 (student t-test). Normal skin represents tissue that was not UV irradiated. BNP - bioadhesive nanoparticle, CPD - cyclobutane pyrimidine dimers, PO – padimate O.
Figure 6
Figure 6. Staining for γH2AX on mouse dorsal epidermal sheets receiving different topical interventions and UVB irradiation (160 J/m2)
(A) Epidermal sheets were prepared 20 hours after exposure to UV-B. (B) The γH2AX+ cells within the epidermis for each intervention were enumerated. The scale bar represents 50 µm. Data are shown as mean ± SD (n=3), **p ≤ 0.01 (student t-test). Normal skin represents tissue that was not UV irradiated. γH2AX – phosphorylated histone H2A variant H2AX, BNP - bioadhesive nanoparticle, NS – not significant, PO – padimate O, UV – ultraviolet.
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