title: Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery.
abstract: The endo-lysosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially the payloads that are susceptible to lysosomal degradation. Current vectors that enable the endo-lysosomal escape of macromolecules such as DNA are limited by their toxicity and by their ability to carry only limited classes of therapeutic agents. In this paper, we report the rapid (<10 min) endo-lysosomal escape of biodegradable nanoparticles (NPs) formulated from the copolymers of poly(DL-lactide-co-glycolide) (PLGA). The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endo-lysosomal compartment, which causes the NPs to interact with the endo-lysosomal membrane and escape into the cytosol. PLGA NPs are able to deliver a variety of therapeutic agents, including macromolecules such as DNA and low molecular weight drugs such as dexamethasone, intracellularly at a slow rate, which results in a sustained therapeutic effect. PLGA has a number of advantages over other polymers used in drug and gene delivery including biodegradability, biocompatibility, and approval for human use granted by the U.S. Food and Drug Administration. Hence PLGA is well suited for sustained intracellular delivery of macromolecules.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
authors.forename: Wen-Zhong
authors.initials: WZ
authors.lastname: Zhou
authors.forename: Swayam
authors.initials: S
authors.lastname: Prabha
authors.forename: Sanjeeb K
authors.initials: SK
authors.lastname: Sahoo
authors.forename: Vinod
authors.initials: V
authors.lastname: Labhasetwar
mesh_terms: D001692:Biological Transport; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D015316:Genetic Therapy; D006131:Growth Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D014162:Transfection
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006131:Growth Inhibitors; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone