title: 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 O2to 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.
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University , 2100 Adelbert Road, Cleveland, Ohio 44106, United States.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Hutnick
authors.affiliation: Department of Dermatology, Case Skin Disease Research Center, Case Western Reserve University/University Hospitals Cleveland Medical Center , Cleveland, Ohio 44106, United States.
authors.forename: Sayeeda
authors.initials: S
authors.lastname: Ahsanuddin
authors.affiliation: Department of Dermatology, Case Skin Disease Research Center, Case Western Reserve University/University Hospitals Cleveland Medical Center , Cleveland, Ohio 44106, United States.
authors.forename: Linna
authors.initials: L
authors.lastname: Guan
authors.affiliation: Department of Dermatology, Case Skin Disease Research Center, Case Western Reserve University/University Hospitals Cleveland Medical Center , Cleveland, Ohio 44106, United States.
authors.forename: Minh
authors.initials: M
authors.lastname: Lam
authors.affiliation: Department of Dermatology, Case Skin Disease Research Center, Case Western Reserve University/University Hospitals Cleveland Medical Center , Cleveland, Ohio 44106, United States.
authors.forename: Elma D
authors.initials: ED
authors.lastname: Baron
authors.affiliation: Department of Macromolecular Science and Engineering, Case Western Reserve University , 2100 Adelbert Road, Cleveland, Ohio 44106, United States.
authors.forename: Jonathan K
authors.identifier: 0000-0001-5869-6942
authors.initials: JK
authors.lastname: Pokorski
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D017646:Organosilicon Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D050091:Dendrimers; D007211:Indoles; D017646:Organosilicon Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C082854:silicon phthalocyanine