PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections

Abstract

Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.

Silicon phthalocyanines: synthesis and resurgent applications

“…The promising activity of Pc-4 (6) in clinical trials 89 has sparked renewed interest in researchers to improve efficacy of Pc-4. [90][91][92][93][94] In parallel, several approaches were adopted to increase the aqueous solubility and biocompatibility leading to development of new SiPc photosensitizers. For example, a SiPc derivative with two bulky permethylated cyclodextrin moieties in the axial positions displayed reduced self-aggregation in the cell culture media and remarkable in-vitro and in-vivo PDT effects.…”

Construction and Characterization of Phthalocyanine-Loaded Particles of Curdlan and Their Photosensitivity

“…Through denaturation and renaturation, helical polysaccharide chains—such as a single helix of v-amylose and a triple helix of Schizophyllan—could form functionalized nanostructures, by incorporating multiple hydrophobic guest molecules into their hydrophobic cavities [ 33 , 38 , 39 , 40 ]. Two nanostructures of this type, loaded with PC, have been developed for drug delivery [ 41 , 42 ]. Using a polymer as a carrier, PC has broad application prospects in drug delivery.…”

Dendrimer-based strategies for cancer therapy: Recent advances and future perspectives

“…PDT is a useful method to destroy cancer cells by reactive oxygen species (ROS) and singlet oxygen that are produced by photosensitizers (PS) when exposed to visible or NIR laser light. The PS/dendrimers nanoformulations can be formed by covalent binding [99,123,124], physical encapsulation [100,125,126], electrostatic interaction [101,102] between PS and dendrimers. Meanwhile the PS can be used as branch unit to synthesize PS-based dendrimers for photodynamic treatment of cancer [127].…”