title: Novel Layer-by-Layer Deposition Technique for the Preparation of Double-Chambered Nanoparticle Formulations.
abstract: In this work, we report a novel method of layer-by-layer (LbL) deposition using concentration tubes that enables faster process and less damage to fragile nanocores than previously described methods. Such methods are generally based on continuous cycles of centrifugation/resuspension for long times and at high speeds, which may eventually lead to the aggregation of the deflocculated suspension of nanoparticles into a compact, non-resuspendable cake. The new method was applied to the preparation of a double-chambered nanocarrier system, which was successfully loaded with a fluorescently labeled model protein (lysozyme) and a model small molecule (fluorescein) in two defined and separate compartments, namely the poly lactide-co-glycolide (PLGA) core (∼110 nm) and an outer shell obtained by LbL surface coating. The new method yielded stable suspensions of drug-loaded, LbL-coated PLGA nanoparticles, while centrifugation at high speeds and long time intervals leads to a compact cake of non-resuspendable aggregates. These nanocarriers were taken up by MDCK cells in vitro, where a colocalization of both model compounds was shown by confocal imaging.
authors.affiliation: School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne, CH-1211, Geneva, 4, Switzerland.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Sakr
authors.affiliation: School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne, CH-1211, Geneva, 4, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Jordan
authors.affiliation: School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne, CH-1211, Geneva, 4, Switzerland.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
mesh_terms: D065567:Absorption, Physiological; D000464:Alginates / Q000737:chemistry; D000818:Animals; D011232:Chemical Precipitation; D004285:Dogs; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004355:Drug Stability; D019793:Fluorescein / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D061985:Madin Darby Canine Kidney Cells; D008956:Models, Chemical; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D000459:Phaeophyceae / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000464:Alginates; D005456:Fluorescent Dyes; D006603:Hexuronic Acids; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid; C421864:hen egg lysozyme; D009113:Muramidase; D019793:Fluorescein
keywords: PLGA; alginate; biomaterials; codelivery; layer-by-layer; nanoparticles; protein delivery