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Review
. 2021 Aug 6;14(8):772.
doi: 10.3390/ph14080772.

Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies

Isabella Portugal  1 , Sona Jain  1 , Patrícia Severino  1 , Ronny Priefer  2
Affiliations
Review

Micro- and Nano-Based Transdermal Delivery Systems of Photosensitizing Drugs for the Treatment of Cutaneous Malignancies

Isabella Portugal et al. Pharmaceuticals (Basel). .

Abstract

Photodynamic therapy is one of the more unique cancer treatment options available in today's arsenal against this devastating disease. It has historically been explored in cutaneous lesions due to the possibility of focal/specific effects and minimization of adverse events. Advances in drug delivery have mostly been based on biomaterials, such as liposomal and hybrid lipoidal vesicles, nanoemulsions, microneedling, and laser-assisted photosensitizer delivery systems. This review summarizes the most promising approaches to enhancing the photosensitizers' transdermal delivery efficacy for the photodynamic treatment for cutaneous pre-cancerous lesions and skin cancers. Additionally, discussions on strategies and advantages in these approaches, as well as summarized challenges, perspectives, and translational potential for future applications, will be discussed.

Keywords: cancer; cutaneous; drug delivery; photodynamic therapy; transdermal.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The developmental timeline of photodynamic therapy through the centuries. Abbr.: hematoporphyrin (HP), photodynamic therapy (PDT), hematoporphyrin derivative (HpD), head-and-neck squamous carcinoma (HNSC), phthalocyanine (Pc).
Figure 2
Figure 2
Current chemical and physical strategies to enhance transdermal drug delivery of photodynamic therapy.
Figure 3
Figure 3
Mechanisms of skin permeation of lipid-based nano-vesicular systems for transdermal drug delivery in photodynamic therapy. (A) Conventional liposomes are superficially retained in the stratum corneum, disrupting and releasing the drug, which continues the epidermal penetration through diffusion. (B) Transfersomes have edge activators (surfactants) in their composition, which confer deformability, allowing for deeper drug release in the skin. (C) Ethosomes have a higher concentration of ethanol in their composition, increasing their flexibility and allowing for deeper drug release in the skin.
Figure 4
Figure 4
Enhanced photodynamic therapy combining neoadjuvant topical depigmentation and liposomal photosensitizing drug delivery to treat resistant melanotic melanoma.
Figure 5
Figure 5
Mechanism of action of fractional laser-assisted photosensitizing drug delivery systems for PDT enhancement.
Figure 6
Figure 6
Mechanism of action of current microneedle (MN)-based systems for photosensitizing drug delivery enhancement in photodynamic therapy. (A) Graphical representation of current microneedling systems applied to the skin. (B) Graphical representation of skin permeation of photosensitizer microneedle-based platforms.
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