Photodynamic Topical Antimicrobial Therapy for Infected Diabetic Foot Ulcers in Patients With Diabetes: A Case Series

Abstract

Diabetic foot ulcers (DFUs) are common, complex, costly complications, associated with frequent recurrences and increased morbidity and mortality. DFUs can be prevented and their healing can be mostly influenced by appropriately and aggressively managing any infection, but the role of antiseptic therapies in reducing healing time lacks sufficient evidence. Several therapeutic interventions have been developed based on the principles of photomedicine to overcome the issue of poor drug circulation in infected areas, with the aim of killing microbial agents while leaving the surrounding host cells unharmed. Such techniques use absorption of photons by specific chromophores. Among these, RLP068 is a tetracationic Zn(II) phthalocyanine derivative activated by exposure to red light, used as a topical treatment for superficial bacterial and fungal infections. The photoactivation of RLP068 results in the production of singlet oxygen and other reactive oxygen species, able to affect a range of cellular targets, including cell membrane and/or wall, cytoplasm, and cellular components, resulting in a rapid, broad range, bactericidal and fungicidal effect. The phase IIa study showed that photoactivated RPL068 is capable of inducing a dose-dependent reduction in total and pathogen microbial load in infected diabetic foot ulcers. In this article, a case series of 22 DFU treated with photoactivated RLP068 at 5 different centers in Italy is presented. Considering microbial agents reduction, ulcer healing facilitation, healing rate (9 DFUs out of 22), and amputation rate (only 1 case over 22), the decrease in the cost of DFU seems to be a point in favor of RLP068 and its cost-effectiveness.

Amplify antimicrobial photo dynamic therapy efficacy with poly-beta-amino esters (PBAEs)

“…aPDT has numerous benefits as potential alternative to antibiotics for the treatment of infections such as skin and tissues that can be accessed with light sources 10 , 12 , 42 ; however a critical drawback is the still relative long treatment time required (in the order of tens of minutes) that impacts the largescale application of this technology 26 . The design of novel and more efficient photosensitisers is generally accompanied by elevated drug costs; similarly, the use of drug delivery systems brings additional costs that must be offset by the enhanced efficacy.…”

“…Photodynamic therapy is a local, repeatable non-invasive technique which might be an effective alternative to antibiotics for the treatment of local infections 9 , periodontitis 10 and diabetic foot ulcer 11 , 12 . The mechanism of action of PDT derives from a light-induced excitation of a photosensitiser (PS) to singlet state and its conversion to triplet state, whose reactivity results in the generation of radicals and ROS 13 , 14 .…”

Amplify Antimicrobial Photo Dynamic Therapy Efficacy With Poly-beta-amino Esters (PBAEs)

“…aPDT has numerous bene ts as potential alternative to antibiotics for the treatment of infections such as skin and tissues that can be accessed with light sources 13,15,39 ; however a critical drawback is the still relative long treatment time required (in the order of tens of minutes) that impacts the largescale application of this technology 25 . The design of novel and more e cient photosensitisers is generally accompanied by elevated drug costs; similarly, the use of drug delivery systems brings additional costs that must be offset by the enhanced e cacy.…”

“…Photodynamic therapy is a local, repeatable non-invasive technique which might be an effective alternative to antibiotics for the treatment of local infections 12 , periodontitis 13 and diabetic foot ulcer 14,15 . The mechanism of action of PDT derives from a light-induced excitation of the PS to singlet state and its conversion to triplet state, whose reactivity results in the generation of radicals and ROS by two different photochemical mechanisms labelled Type I and Type II 16,17 .…”

Photodynamic disinfection and its role in controlling infectious diseases

“…Additionally, amputation was prevented in 95% of the cases. The authors remark that this PDDI treatment healed infected lesions that had already been treated unsuccessfully with all available methods (local and systemic) and thus prevented amputation, which is considered the last resort treatment [ 197 ]. Overall, the clinical studies involving RLP068 (PS 28 ) show its potential for the treatment of infected leg ulcers, a fact clearly highlighted by two recent reviews [ 196 , 206 ].…”