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Supramolecular modification of commonly used photoactive drugs regarding their photochemistry, stability, and safety

Kang, Xu
http://orcid.org/0000-0002-1957-6910
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1626456443488287

Abstract Details

2021, PhD, University of Cincinnati, Pharmacy: Pharmaceutical Sciences.
Photoactive compounds can be found in several areas of our daily life. For example, several acne drugs are photoactive, like retinoids and benzoyl peroxide; and sunscreens that absorb or reflect UV rays to keep our skin from aging and prevent us from getting skin cancer, are photoactive too. Both sunscreens and anti-acne actives are photoactive in nature; however, the inherent instability of photoactive drugs can cause phototoxicity, and/or cause long-term side effects due to skin penetration. Hence, photoactives are in general very concerning for industry and consumers and require thorough investigation. Photodegradation of actives leads to skin irritation after drug administration. Most patients experience skin irritation, redness, and burning when their skin is exposed to light, especially when exposed to UV rays. Benzoyl peroxide (BPO), as an anti-acne drug, has been a focus in clinical research for many years due to its powerful broad-spectrum antimicrobial effect; however, the exact mechanism of how BPO works is still unclear. Unlike antibiotics, no bacterial resistance has been found for BPO, but the instability, free radical irritation, and phototoxicity post-application of BPO are growing concerns for industry and consumers. Oxybenzone (OXB) is a sunscreen active ingredient that can penetrate the skin and is found in the blood and urine of most humans, which may do long-term harm to our health. The purpose of this study is to propose a novel methodology to combine photoactive compounds with macrocycles through non-covalent interactions to address the current concerns for the two drugs: BPO and OXB. Macrocycles are highly important in the understanding of supramolecular chemistry. They differ from linear molecules in that they are relatively large molecules with hydrophobic cavities that can host small molecules; commonly bowl-shaped, cylindrical, and tubular. Previous studies of macrocycles have shown that they can alter the physical and chemical properties of encapsulated guest molecules. In this project, we examined how the host environment affects the drug stability and excited-state reaction intermediates of photoactive compounds. We report the complexation of BPO with C-alkylpyrogallol[4]arenes (PgCn, where n= 5, 6, 11) macrocycle through non-covalent interactions. We also investigated the formation of host-guest complexes between C-methylresorcin[4]arene and OXB. NMR spectroscopy confirmed the formation of a weak host-guest complex and molecular dynamics docking simulations indicated that this complex likely had a 1:1 stoichiometry. Furthermore, skin permeation testing revealed that complexation by C-methylresorcin[4]arene significantly reduced the amount of OXB that permeated skin. These results show the potential of supramolecular complexation for improving the stability and decreasing the skin permeability of OXB, thus limiting harmful side effects. We also did pilot studies on avobenzone and curcumin to demonstrated how they can form complexations with macrocycles. This research is expected to make a significant contribution in terms of using supramolecular chemistry to stimulate skincare science. The multifaceted outcome could include a decrease in penetration of sunscreen active ingredients, decrease in skin irritation, reduction in fine lines caused by free radicals, improvement in the overall safety of phototoxic drugs, and enhancement of both their photostability and thermostability.
Harshita Kumari, Ph.D. (Committee Chair)
Kavssery Ananthapadmanabhan, ENG.SC.D. (Committee Member)
Anna Gudmundsdottir, Ph.D. (Committee Member)
Gerald Kasting, Ph.D. (Committee Member)
Nalinikanth Kotagiri, Ph.D. (Committee Member)
146 p.
Pharmaceuticals
Supramolecular chemistry; Acne drug; Photoactive compounds; Sunscreens; Skincare; NMR

Recommended Citations

Citations

  • Kang, X. (2021). Supramolecular modification of commonly used photoactive drugs regarding their photochemistry, stability, and safety [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1626456443488287

    APA Style (7th edition)

  • Kang, Xu. Supramolecular modification of commonly used photoactive drugs regarding their photochemistry, stability, and safety. 2021. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1626456443488287.

    MLA Style (8th edition)

  • Kang, Xu. "Supramolecular modification of commonly used photoactive drugs regarding their photochemistry, stability, and safety." Doctoral dissertation, University of Cincinnati, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1626456443488287

    Chicago Manual of Style (17th edition)

ucin1626456443488287
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This open access ETD is published by University of Cincinnati and OhioLINK.