A sunblock based on bioadhesive nanoparticles

Journal name:
Nature Materials
Volume:
14,
Pages:
1278–1285
Year published:
DOI:
doi:10.1038/nmat4422
Received
Accepted
Published online

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 5wt% 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.

At a glance

Figures

  1. Comparison of BNP-based sunscreen and commercial sunscreen.
    Figure 1: Comparison of BNP-based sunscreen and 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 that 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.

  2. Evaluation of BNP adhesion.
    Figure 2: Evaluation of BNP adhesion.

    a, Surface aldehyde concentration on nanoparticles was recorded as a function of incubation time with NaIO4. Data are shown as mean ± s.d. (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 (0min) represents NNPs (non-adhesive control). Data are shown as mean ± s.d. (n = 4). c, BNPs and NNPs at 1mgml−1 were incubated on pig skin for six hours in a humidity chamber at 32°C. Scale bars, 200μm. d, The fluorescence was quantified and normalized to the average fluorescence of BNPs. Data are shown as mean ± s.d. (n = 10), P < 0.0001 (Student t-test). e, BNPs encapsulating an infrared dye, IR-780, were applied on the dorsal skin of mice and their skin retention was imaged with Xenogen at different time points. f, The fluorescence was quantified and normalized to the fluorescence intensity at time zero. Error bars represent standard deviations of measurements on 4 animals. 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), their skin retention was imaged with Xenogen. h, The fluorescence after wiping or washing was quantified and normalized to the fluorescence intensity at time zero.

  3. Synthesis and in vitro evaluation of PO/BNPs.
    Figure 3: Synthesis and in vitro evaluation of PO/BNPs.

    a, TEM image of PO/BNPs. Scale bar, 200nm. b, PO retention within PO/BNPs in artificial human sweat at 32°C and 37°C. Data are shown as mean ± s.d. (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 0.01mgml−1, and sunscreen dissolved in mineral oil (Sunscreen/oil) at 0.01mgml−1 of active ingredients. UV filters within their vehicles were scanned for UV absorbance between 260 and 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 ± s.d. (n = 8), P < 0.0001. NS, not significant.

  4. Histology of dorsal mouse skin sections receiving different topical interventions three days after high dose UV (2,160[thinsp]J[thinsp]m-2).
    Figure 4: Histology of dorsal mouse skin sections receiving different topical interventions three days after high dose UV (2,160Jm−2).

    aj, Topical interventions included normal skin without UV exposure (a,b), and with UV exposure with protection from sunscreen (c,d), PO/BNPs (e,f), blank BNPs (g,h) and no protection (i,j). There was significant acanthosis (double-headed arrow) with prominent rete ridges (yellow 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,l, Epidermal thickness (k) and percentage area of keratin (l) within the dorsal skin after receiving topical interventions and UV irradiation. Scale bar, 100μm. Haematoxylin and eosin staining (a,c,e,g,i). Trichrome staining (b,d,f,h,j). P < 0.05 compared with all other treatment groups.

  5. CPD staining of mouse dorsal epidermal sheets after receiving different topical interventions and UVB irradiation (160[thinsp]J[thinsp]m-2).
    Figure 5: CPD staining of mouse dorsal epidermal sheets after receiving different topical interventions and UVB irradiation (160Jm−2).

    a, Epidermal sheets were prepared five minutes after exposure to UVB. Scale bar, 50μm. b, The fluorescence of CPD on skin receiving different topical interventions was quantified. Normal skin represents tissue that was not UV irradiated. Data are shown as mean ± s.d. (n = 3), P < 0.01 (Student t-test). NS, not significant.

  6. Staining for [gamma]H2AX on mouse dorsal epidermal sheets receiving different topical interventions and UVB irradiation (160[thinsp]J[thinsp]m-2).
    Figure 6: Staining for γH2AX on mouse dorsal epidermal sheets receiving different topical interventions and UVB irradiation (160Jm−2).

    a, Epidermal sheets were prepared 20h after exposure to UVB. Scale bar, 50μm. b, The γH2AX+ cells within the epidermis for each intervention were enumerated. Normal skin represents tissue that was not UV irradiated. Data are shown as mean ± s.d. (n = 3), P ≤ 0.01 (Student t-test). NS, not significant.

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Author information

  1. These authors contributed equally to this work.

    • Yang Deng &
    • Asiri Ediriwickrema

Affiliations

  1. Department of Biomedical Engineering, Yale University, 55 Prospect Street, New Haven, Connecticut 06511, USA

    • Yang Deng,
    • Asiri Ediriwickrema,
    • Fan Yang &
    • W. Mark Saltzman
  2. Department of Dermatology, Yale University, 333 Cedar Street, New Haven, Connecticut 06520, USA

    • Julia Lewis &
    • Michael Girardi

Contributions

Y.D., A.E., J.L., F.Y., M.G. and W.M.S. designed the experiments. Y.D., A.E., F.Y. and J.L. performed the experiments. All the authors were involved in the analyses and interpretation of data. Y.D., A.E., M.G. and W.M.S. wrote the paper, with the help of the co-authors.

Competing financial interests

The authors declare no competing financial interests.

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