title: Three-Layered Biodegradable Micelles Prepared by Two-Step Self-Assembly of PLA-PEI-PLA and PLA-PEG-PLA Triblock Copolymers as Efficient Gene Delivery System.
abstract: "Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.
authors: Department of Chemistry, The University of Memphis, 213 Smith Chemistry Building, Memphis, Tennessee, 38152, USA.
authors: Daniel G
authors: DG
authors: Abebe
authors: College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue., Detroit, Michigan, 48201, USA.
authors: Rima
authors: R
authors: Kandil
authors: College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue., Detroit, Michigan, 48201, USA.
authors: Teresa
authors: T
authors: Kraus
authors: College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue., Detroit, Michigan, 48201, USA.
authors: Maha
authors: M
authors: Elsayed
authors: College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue., Detroit, Michigan, 48201, USA. olivia.merkel@wayne.edu.
authors: Olivia M
authors: OM
authors: Merkel
authors: Department of Chemistry, The University of Memphis, 213 Smith Chemistry Building, Memphis, Tennessee, 38152, USA. tfjiwara@memphis.edu.
authors: Tomoko
authors: T
authors: Fujiwara
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002412:Cations; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D000067493:Dynamic Light Scattering; D018014:Gene Transfer Techniques; D051379:Mice; D008823:Micelles; D008970:Molecular Weight; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D000067996:RAW 264.7 Cells; D012996:Solutions; D055672:Static Electricity; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D008823:Micelles; D011091:Polyesters; D012996:Solutions; D013501:Surface-Active Agents; C000604720:poly(lactide)-b-polyethyleneimine-b-poly(lactide); C507889:polylactide-polyethylene glycol-polylactide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA
keywords: block copolymers; gene delivery; micelles; poly(lactic acid); polyethyleneimine