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Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal
Melanie A Hutnick1, Sayeeda Ahsanuddin2, Linna Guan2
1Department of Macromolecular Science and Engineering, Case Western Reserve University , 2100 Adelbert Road, Cleveland, Ohio 44106, United States.
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 O2 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.
Insights
This study introduces a novel nanoparticle drug delivery system for photodynamic therapy (PDT) to combat drug-resistant Candida albicans infections. The new formulation effectively kills fungi without causing solvent toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Mycology
Background:
- Fungal infections, particularly those caused by Candida albicans, are a significant global health concern.
- Increasing antifungal resistance necessitates novel therapeutic strategies.
- Photodynamic therapy (PDT) offers a promising alternative, but photosensitizer formulation remains a challenge.
Purpose of the Study:
- To develop and evaluate a nanoparticle-based drug delivery vehicle for the hydrophobic photosensitizer Pc 4.
- To improve the formulation and delivery of Pc 4 for treating fungal infections.
- To assess the efficacy of encapsulated Pc 4 in combating drug-resistant Candida albicans.
Main Methods:
- Synthesis of a poly(amidoamine) dendrimer-based delivery vehicle with PEGylated amine chain ends.
- Encapsulation of the photosensitizer Pc 4 within the dendrimer nanoparticles.
- In vitro studies using Candida albicans to evaluate ROS generation and fungal cell obliteration upon photoactivation.
Main Results:
- The dendrimer vehicle successfully formulated the hydrophobic photosensitizer Pc 4, enhancing its water solubility.
- Encapsulated Pc 4 retained its potency, effectively generating reactive oxygen species (ROS) upon photoactivation.
- The nanoparticle formulation demonstrated significant efficacy in killing drug-resistant Candida albicans in vitro, with reduced solvent toxicity.
Conclusions:
- A novel nanoparticulate delivery system for Pc 4 has been successfully developed.
- This formulation overcomes the challenges associated with hydrophobic photosensitizers, improving PDT applicability for fungal infections.
- The developed system offers a viable strategy for treating drug-resistant Candida albicans infections.

