Drug delivery strategies for porphyrin-based photosensitizers in photodynamic antimicrobial chemotherapy

In the face of increasing antimicrobial resistance (AMR) and the looming threat of a return to a pre-antibiotics era, the exploration of alternative antimicrobial strategies becomes imperative. Among these, Photodynamic Antimicrobial Chemotherapy (PACT) stands out as a promising solution due to its multi-target principle, diverging from the key-lock mechanism inherent in conventional antibiotics. However, the hydrophobic nature, non-targeted distribution, stability issues, and limited tissue penetration of photosensitizers (PSs), particularly the extensively studied porphyrin-based compounds, pose structural limitations impacting their bioavailability and effective delivery to target sites. Therefore, various delivery strategies are adopted to improve their effectiveness in PACT. This includes attaching the PS to a variety of delivery vehicles such as nanoparticles, and liposomes, or encapsulating them in nanostructures, such as micelles or dendrimers. This helps protect the PS from degradation, improve their solubility and bioavailability, and enhance their photophysical and photochemical properties, ultimately improving their effectiveness in PACT. In this paper, recent studies focusing on strategies used to improve the delivery of porphyrin-based PS in PACT are reviewed. Porphyrins have significant potential as photosensitizers in photodynamic antimicrobial chemotherapy (PACT), but their hydrophobic nature and aggregation tendencies limit their clinical applications. Researchers have addressed these issues by employing diverse delivery strategies, including nanoparticle attachment and encapsulation in nanostructures like liposomes and micelles. These approaches enhance porphyrin solubility, stability, and photophysical properties, ultimately improving their effectiveness in PACT, as comprehensively discuessed in this review.