Drug Delivery Strategies for Avobenzone: A Case Study of Photostabilization

Abstract

Several developments and research methods are ongoing in drug technology and chemistry research to elicit effectiveness regarding the therapeutic activity of drugs along with photoprotection for their molecular integrity. The detrimental effect of UV light induces damaged cells and DNA, which leads to skin cancer and other phototoxic effects. The application of sunscreen shields to the skin is important, along with recommended UV filters. Avobenzone is widely used as a UVA filter for skin photoprotection in sunscreen formulations. However, keto-enol tautomerism propagates photodegradation into it, which further channelizes the phototoxic and photoirradiation effects, further limiting its use. Several approaches have been used to counter these issues, including encapsulation, antioxidants, photostabilizers, and quenchers. To seek the gold standard approach for photoprotection in photosensitive drugs, combinations of strategies have been implemented to identify effective and safe sunscreen agents. The stringent regulatory guidelines for sunscreen formulations, along with the availability of limited FDA-approved UV filters, have led many researchers to develop perfect photostabilization strategies for available photostable UV filters, such as avobenzone. From this perspective, the objective of the current review is to summarize the recent literature on drug delivery strategies implemented for the photostabilization of avobenzone that could be useful to frame industrially oriented potential strategies on a large scale to circumvent all possible photounstable issues of avobenzone.

Keywords: avobenzone; drug delivery; encapsulation; photostabilization; sunscreen.

Figure 1

Schematics of the utilization of sunscreens to protect against damaging impacts of sunrays wherein UV rays are responsible for noxious effects attributed to sunlight. Three bands make up the UV region, which has a wavelength range of 100–400 nm: UVA (315–400 nm), UVB (280–315 nm), and UVC (100–280 nm). The ozone layer is currently shielded from UVC rays. High-intensity UVB radiation causes more rapid harm than low-energy UVA radiation, which can penetrate further into the skin and cause long-term impact. Utilizing inorganic UV filters can create a barrier that keeps UV rays from penetrating the skin. This barrier could either reflect or scatter light.

Figure 2

Structure and keto-enol tautomerism of avobenzone.

Figure 3

Structure-activity relationship and photodegradation of avobenzone: The substitution of the R group on ring ‘A’ of avobenzone with electron-withdrawing groups increases the photostability, while electron-donating groups destabilize it (entries 1, 2 and 3). Furthermore, blocking the keto-enol tautomerism by replacing the acidic hydrogen with the methyl group also contributes positively to the photostability of avobenzone (entry 4). Avobenzone degrades into 4-t-butyl benzoic acid and 4-methoxy benzoic acid [37,38].

Figure 4

Schematic representation of sunscreen agent-loaded micro/nanocarriers wherein the delivery systems that surround the sunscreen agent prevent skin penetration and limit exposure to possibly dangerous substances. Encapsulation and photostabilizer compounds are used to make photostable formulations for photounstable UV filters such as AVOB. Generally, a stable UV filter after UV ray exposure undergoes an excited state and returns to a stable ground state by using phosphorescence and fluorescence. After prolonged UV exposure, such UV filters undergo interstate system crossing to form photograded metabolites, which further induce skin cancer.

Figure 5

Avobenzone & β Cyclodextrin Inclusion Complex. AVOB undergoes photodegradation through keto-enol tautomerism to produce photodegraded products, which further induces phototoxicity. Such issues are countered by effective encapsulation by β-cyclodextrin by forming an avobenzone photostable comp.

Figure 6

Mechanism of reactive oxygen species interactions with the body to induce skin cancer and other side effects. Several antioxidants are used to counter damage, such as DNA damage, apoptosis, and cell proliferation, induced by ROS. Different process parameters, including metabolic reactions in peroxisomes, oxidative phosphorylation in mitochondria and enzymatic reactions, play pivotal roles in the generation of ROS. Endogenous antioxidants are implemented to stabilize reactive oxygen species. In the absence of their interference, the enhanced oxidative stress will form several harmful effects on the body that need to be addressed by exogenous antioxidant agents.

Figure 7

The nanodispersion of titanium dioxide nanoparticles and zinc oxide microparticles is achieved with a shaker mixer by using an alumina ball. Prior to mixing, titanium dioxide nanoparticles were prepared by using hydrothermal and ultrasonic treatment. The shaker mixer ensures agglomeration breaking and provides photostable nanodispersions ready for drug use.

Figure 8

The interaction of organic and inorganic UV filters from sunscreen formulation with UV light. The organic UV filter undergoes conformational changes after UV exposure, followed by heat release. The organic UV filter works through the reflection, scattering or absorption of UV light.