Preparation and characterization of poly(DL-lactide-co-glycolide) nanoparticles for siRNA delivery.
Synthetic short interfering RNA (siRNA) is promising for specific and efficient knockdown of disease-related genes. However, in vivo application of siRNA requires an effective delivery system. Commonly used siRNA carriers are based on polycations, which form electrostatic complexes with siRNA. Such poly- or lipoplexes are of limited use in vivo due to severe problems associated with toxicity, serum instability and non-specific immune-responses. The aim of the present study was to prepare uniformly sized nanoparticles (NPs) with a high load of siRNA by use of the safe and biodegradable poly-(DL-lactide-co-glycolide) (PLGA) polymer without including polycations. The siRNA was encapsulated in the core of NPs by the double emulsion solvent evaporation method. To optimize the NP formulation, the effects of important formulation and processing parameters were investigated systematically. Generally, spherical siRNA-loaded NPs (<300 nm, PDI<0.2, zeta potential -40 mV) were obtained. An encapsulation efficiency of up to 57% was achieved by adjusting the inner water phase volume, the PLGA concentration, the first emulsification sonication time, and stabilization of the water-oil interface with serum albumin. The integrity of siRNA was preserved during the preparation. Preparation of core-loaded siRNA-NPs based on PLGA and no cationic excipient seems possible and promising for delivery of siRNA.
Cun
Dongmei
D
Department of Pharmaceutics and Analytical Chemistry, The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Foged
Camilla
C
Yang
Mingshi
M
Frøkjaer
Sven
S
Nielsen
Hanne Mørck
HM
D000107:Acetylation; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics; D019344:Lactic Acid / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry* / Q000235:genetics; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013010:Sonication; D055672:Static Electricity; D013499:Surface Properties; D013997:Time Factors; D014867:Water / Q000737:chemistry
D004337:Drug Carriers; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D014867:Water; D049452:Green Fluorescent Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid