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

Biomacromolecules. 2017 Feb 13;18(2):379-385. doi: 10.1021/acs.biomac.6b01436. Epub 2017 Jan 24.

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.

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Apoptosis / drug effects
  • Candida albicans / drug effects*
  • Candidiasis / drug therapy
  • Dendrimers / administration & dosage
  • Dendrimers / chemistry*
  • Drug Delivery Systems*
  • Indoles / administration & dosage
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Light
  • Organosilicon Compounds / administration & dosage
  • Organosilicon Compounds / chemistry
  • Organosilicon Compounds / pharmacology*
  • Photochemotherapy*
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Antifungal Agents
  • Dendrimers
  • Indoles
  • Organosilicon Compounds
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • silicon phthalocyanine