title: SiRNA drug delivery by biodegradable polymeric nanoparticles.
abstract: RNA interference (RNAi) is an emerging technology in which the introduction of double-stranded RNA (dsRNA) into a diverse range of organisms and cell types causes degradation of the complementary mRNA. It offers a broad spectrum of applications in both biological and medical research. Small interference RNA (siRNA) was recently explored for its therapeutical potential. However, the drug delivery of siRNA oligos is very novel and is in great need of future research. To this end, a biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle drug carrier system was prepared to load siRNA oligos with desired physicochemical properties. The nanoparticles were characterized by scanning electron microscopy and laser diffraction particle sizer. The delivery of siRNA into the targeted 293T cells was observed using fluorescent-labeled double-stranded Cy3-oligos. The model siRNA oligos, si-GFP-RNA, were also successfully loaded into PLGA nanoparticles and delivered in 293T cells. The gene silencing effect and the inhibition of GFP expression were investigated using fluorescent microscopy. Both positive and negative controls were used to compare with the new siRNA nanoparticle delivery system. It was found that nanoparticles offered both effective delivery of siRNA and prominent GFP gene silencing effect. Compared to conventional carrier systems, the new biodegradable polymeric nanoparticle system may also offer improved formulation stability, which is practically beneficial and may be used in the future clinical studies of siRNA therapeutics.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, 75 Dekalb Avenue, NY 11201, USA.
authors.forename: Xudong
authors.initials: X
authors.lastname: Yuan
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Appu
authors.initials: A
authors.lastname: Rathinavelu
authors.forename: Jinsong
authors.initials: J
authors.lastname: Hao
authors.forename: Madhusudhanan
authors.initials: M
authors.lastname: Narasimhan
authors.forename: Matthew
authors.initials: M
authors.lastname: He
authors.forename: Viviene
authors.initials: V
authors.lastname: Heitlage
authors.forename: Linda
authors.initials: L
authors.lastname: Tam
authors.forename: Sana
authors.initials: S
authors.lastname: Viqar
authors.forename: Mojgan
authors.initials: M
authors.lastname: Salehi
mesh_terms: D020341:Absorbable Implants; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology*; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid