title: Specific uptake of folate-decorated triamcinolone-encapsulating nanoparticles by retinal pigment epithelium cells enhances and prolongs antiangiogenic activity.
abstract: We are proposing folate-decorated polymeric nanoparticles as carriers of poorly soluble drug molecules for intracellular and prolonged delivery to retinal pigment epithelium (RPE) cells. RPE is a monolayer of epithelial cells that forms the outer blood-retinal barrier in the posterior segment of the eye, and is also implicated in the pathology of, such as neovascularization in age-related macular degeneration (AMD). In this study, folate-functionalized poly(ethylene glycol)-b-polycaprolactone (folate-PEG-b-PCL) were synthesized for assembling into nanoparticles of ~130nm. These nanoparticles were internalized into ARPE-19 (human RPE cell line) via receptor-mediated endocytosis, and the cellular uptake was significantly higher than particles without folate modification. Triamcinolone acetonide (TA) was efficiently encapsulated (>97%) into the folate-decorated nanoparticles and was slowly released over a period of 4 weeks at pH 5.5 and 8 weeks at pH 7.4. The enhanced uptake and controlled release resulted in prolonged anti-angiogenic gene expression of RPE cells. In cell culture, the down-regulation of vascular endothelial growth factor (VEGF) and up-regulation of pigment epithelium derived factor (PEDF) lasted for at least 3 weeks. Unlike benzyl alcohol, the surfactant found in commercial formulation, folate-modified nanoparticles were non-toxic. Furthermore, TA became less cytotoxic by being encapsulated in the nanoparticles. Our findings suggest that folate-PEG-PCL nanoparticles are promising drug carriers for RPE targeting.
authors: Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors: Wai-Leung Langston
authors: WL
authors: Suen
authors: Ying
authors: Y
authors: Chau
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D005136:Eye Proteins / Q000235:genetics; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D009414:Nerve Growth Factors / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000166:cytology*; D015843:Serpins / Q000235:genetics; D014221:Triamcinolone / Q000737:chemistry / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005136:Eye Proteins; D005492:Folic Acid; D007783:Lactones; D009414:Nerve Growth Factors; D011092:Polyethylene Glycols; D015843:Serpins; D014221:Triamcinolone; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C467484:VEGFA protein, human; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone)