Transdermal therapeutic polymer: in situ synthesis of biocompatible polymer using 5-aminolevulinic acid as a photosensitizer precursor and a polymer initiator

Abstract

Melanoma is the most malignant skin tumor caused by the malignancy of melanocytes that produce the melanin pigment. Various methods have been developed to combat melanoma, with photodynamic therapy (PDT) gaining the spotlight for its ability to eliminate cancer cells by generating reactive oxygen species through light-sensitive photosensitizers. 5-aminolevulinic acid (5-ALA) is the most commonly used PDT agent, which could be converted to the PpIX photosensitizer molecule within cancer cells. However, its high hydrophilicity limits effective transdermal and oral delivery. In this work, we present a novel polymer formulation, named 5-AP, designed for the transdermal delivery of 5-ALA to deep melanoma tumor sites. 5-AP was prepared by the in situ polymerization of dimethylsiloxane, using 5-ALA as a photosensitizer precursor and a ring-opening polymerization initiator. 5-AP exhibited enhanced hydrophobicity compared to 5-ALA, facilitating improved transdermal penetration. In a melanoma mouse model, 5-ALA was released from the polymer and then converted to PpIX, emitting fluorescence and demonstrating high tumor treatment efficacy under laser irradiation. We believe these findings can usher in a new era of transdermal photodynamic therapy.