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Science Highlight: December 14, 2015

Bioengineered sunscreen blocks skin penetration and toxicity

New sunscreen encased in nanoparticles eliminates cancer-causing potential of traditional sunscreens

A research team including NIBIB-funded scientists has developed a nanotechnology-based sunscreen that provides excellent protection from ultraviolet (UV) damage while eliminating a number of harmful effects of currently used sunscreens. The team encapsulated the UV-blocking compounds in bio-adhesive nanoparticles, which adhere to the skin well, but do not penetrate beyond the skin’s surface. These properties resulted in highly effective UV protection in a mouse model, without the adverse effects observed with commercial sunscreens, including penetration into the bloodstream and generation of reactive oxygen species, which can damage DNA and lead to cancer.

Commercial sunscreens use compounds that effectively filter out damaging UV light. However, there is concern that these agents have a variety of harmful effects due to penetration past the surface skin. For example, these products have been found in human breast tissue and urine and are known to disrupt the normal function of some hormones. Also, the exposure of the UV filters to light can produce toxic reactive oxygen species that are destructive to cells and tissues and can cause tumors through DNA damage. 

BNPs adhere to mouse skin for a day but exfoliate by day 5.

BNPs remain on skin for a full day but are gone due to normal exfoliation in five days. Credit: Macmillan Publishers Ltd1

“This work applies a novel bioengineering idea to a little known but significant health problem, adds Jessica Tucker, Ph.D., Director of the NIBIB Program in Delivery Systems and Devices for Drugs and Biologics. “While we are all familiar with the benefits of sunscreen, the potential toxicities from sunscreen due to penetration into the body and creation of DNA-damaging agents are not well known. Bioengineering sunscreen to inhibit penetration and keep any DNA-damaging compounds isolated in the nanoparticle and away from the skin is a great example of how a sophisticated technology can be used to solve a problem affecting the health of millions of people.”

Bioengineers and dermatologists at Yale University in New Haven, Connecticut combined their expertise in nanoparticle-based drug delivery and the molecular and cellular characteristics of the skin to address these potential health hazards of current commercial sunscreens. The results of their collaboration were reported in the September issue of Nature Materials.1

Minute vessels filled with sunscreen

The group encapsulated a commonly used sunscreen, padimate O (PO), inside a nanoparticle (a very small molecule often used to transport drugs and other agents into the body). PO is related to the better-known sunscreen PABA.

The bioadhesive nanoparticle containing the sunscreen PO was tested on pigs for penetration into the skin. A control group of pigs received the PO alone, not encapsulated in a nanoparticle. The PO penetrated beyond the surface layers of skin where it could potentially enter the bloodstream through blood vessels that are in the deeper skin layers. However, the PO inside the nanoparticle remained on the surface of the skin and did not penetrate into deeper layers. 

cross-sections show similar UV protection from sunscreen alone and encapsulated in BNPs

Mouse skin is protected equally by sunscreen alone and encapsulated in BNPs. b. No UV exposure, d. UV plus sunscreen, f. UV plus sunscreen encapsulated in BNPs, h. UV with no protection. Credit: Macmillan Publishers Ltd1

Because the bioadhesive nanoparticles, or BNPs are larger than skin pores it was somewhat expected that they could not enter the body by that route. However, skin is full of hair follicles that are larger than BNPs and so could be a way for migration into the body. Surprisingly, BNPs did not pass through the hair follicle openings either. Tests indicated that the adhesive properties of the BNPs caused them to stick to the skin surface, unable to move through the hair follicles.

Further testing showed that the BNPs were water resistant and remained on the skin for a day or more, yet were easily removed by towel wiping. They also disappeared in several days through natural exfoliation of the surface skin.

BNPs enhance the effect of sunscreen

An important test was whether the BNP-encapsulated sunscreen retained its UV filtering properties. The researchers used a mouse model to test whether PO blocked sunburn when encapsulated in the BNPs. The BNP formulation successfully provided the same amount of UV protection as the commercial products applied directly to the skin of the hairless mouse model. Surprisingly, this was achieved even though the BNPs carried only a fraction (5%) of the amount of commercial sunblock applied to the mice.

Finally, the encapsulated sunscreen was tested for the formation of damaging oxygen-carrying molecules known as reactive oxygen species, (ROS) when exposed to UV light. The researchers hypothesized that any ROS created by the sunscreen’s interaction with UV would stay contained inside the BNP, unable to damage surrounding tissue. Following exposure to UV light, no damaging ROS were detected outside of the nanoparticle, indicating that any harmful agents that were formed remained inside of the nanoparticle, unable to make contact with the skin. 

BNPs wipe off of skin with towel but remain adhered after water exposure

BNPs were easily wiped away with a towel (T) but remain on skin following water exposure (W). Credit: Macmillan Publishers Ltd1

“We are extremely pleased with the properties and performance of our BNP formulation,” says senior author Mark Saltzman, Ph.D., Yale School of Engineering and Applied Science. “The sunscreen loaded BNPs combine the best properties of an effective sunscreen with a safety profile that alleviates the potential toxicities of the actual sunscreen product because it is encapsulated and literally never touches the skin.” Adds co-senior author, Michael Girardi, M.D. “Our nanoparticles performed as expected, however, these are preclinical findings. We are now in a position to assess the effects on human skin.”

The work was supported by the National Institutes of Health through grant EB000487 from the National Institute of Biomedical Imaging and Bioengineering, and grants CA102703 and CA149128 from the National Cancer Institute. Additional funding was provided by the Yale School of Medicine Office of Student Research, and the Howard Hughes Medical Research Fellowship.

1. A sunblock based on bioadhesive nanoparticles. Deng Y, Ediriwickrema A, Yang F, Lewis J, Girardi M, Saltzman WM. Nat Mater. 2015 Sep 28

Health Terms: 
Biomaterials,
Cancer,
Nanotechnology