title: Controlled Endolysosomal Release of Agents by pH-responsive Polymer Blend Particles.
abstract: OBJECTIVE
  A key step of delivering extracellular agents to its intracellular target is to escape from endosomal/lysosomal compartments, while minimizing the release of digestive enzymes that may compromise cellular functions. In this study, we examined the intracellular distribution of both fluorecent cargoes and enzymes by a particle delivery platform made from the controlled blending of poly(lactic-co-glycolic acid) (PLGA) and a random pH-sensitive copolymer.
  
  
  METHODS
  We utilized both microscopic and biochemical methods to semi-quantitatively assess how the composition of blend particles affects the level of endosomal escape of cargos of various sizes and enzymes into the cytosolic space.
  
  
  RESULTS
  We demonstrated that these polymeric particles enabled the controlled delivery of cargos into the cytosolic space that was more dependent on the cargo size and less on the composition of blend particles. Blend particles did not induce the rupture of endosomal/lysosomal compartments and released less than 20% of endosomal/lysosomal enzymes.
  
  
  CONCLUSIONS
  This study provides insight into understanding the efficacy and safety of a delivery system for intracellular delivery of biologics and drugs. Blend particles offer a potential platform to target intracellular compartments while potentially minimizing cellular toxicity.
authors.affiliation: Department of Biological Structure, University of Washington School of Medicine, Seattle, WA, 98195, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhan
authors.forename: Kenny K
authors.initials: KK
authors.lastname: Tran
authors.forename: Liguo
authors.initials: L
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
mesh_terms: D000165:Acridine Orange / Q000008:administration & dosage; D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D004705:Endocytosis; D011992:Endosomes / Q000201:enzymology / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D008689:Methacrylates; D004364:Pharmaceutical Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000165:Acridine Orange; C049840:2-(dimethylamino)ethyl methacrylate; C016284:butyl methacrylate