title: Gelatin nanocarrier enables efficient delivery and phototoxicity of hypocrellin B against a mice tumour model.
abstract: Nanoparticles formulated from biodegradable and natural polymer gelatin, were investigated for their potential to enable efficient delivery and enhanced efficacy of a well-known photodynamic agent, Hypocrellin B (HB). The HB-loaded poly(ethylene glycol) modified gelatin nanoparticles (HB-PEG-GNP) possessed near-spherical shape, with particle size in the range of 292 +/- 42 nm, and demonstrated characteristic optical properties for photodynamic therapy (PDT). Photophysical studies of the HB-PEG-GNP demonstrated photogeneration of reactive oxygen species (ROS). The nanoparticles were tested for cellular uptake in vitro, on Daltons' Lymphoma Ascites (DLA) cells and demonstrated dose dependent phototoxicity upon visible light treatment. HB-PEG-GNP induced mitochondrial damage, as investigated by JC-1 staining, leading to apoptotic cell death. Biodistribution measurements revealed that nanoformulation reduces liver uptake of HB-PEG-GNP and increases tumour uptake with time. In vivo PDT studies in solid tumour bearing mice showed markedly significant regression (38.5 +/- 2.2%, p < 0.05) for HB-PEG-GNP treated mice in contrast to those treated with free HB (29.36 +/- 1.62%). The present study reveals gelatin nanocarrier to be an effective drug delivery system for enhancement of therapeutic efficacy of the PDT agent, HB.
authors.affiliation: School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, (TN), India.
authors.forename: Anish
authors.initials: A
authors.lastname: Babu
authors.forename: Kadarkaraithangam
authors.initials: K
authors.lastname: Jeyasubramanian
authors.forename: Paramasamy
authors.initials: P
authors.lastname: Gunasekaran
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murugesan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005780:Gelatin / Q000737:chemistry*; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011809:Quinones / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D011809:Quinones; D017382:Reactive Oxygen Species; D010569:Perylene; D005780:Gelatin; C064522:hypocrellin B