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Preparation and characterization of poly(DL-lactide-co-glycolide) nanoparticles for siRNA delivery.
- Source :
-
International journal of pharmaceutics [Int J Pharm] 2010 May 05; Vol. 390 (1), pp. 70-5. Date of Electronic Publication: 2009 Oct 15. - Publication Year :
- 2010
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Abstract
- 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.<br /> (Copyright 2009. Published by Elsevier B.V.)
- Subjects :
- Acetylation
Drug Carriers chemical synthesis
Green Fluorescent Proteins genetics
Microscopy, Electron, Transmission
Particle Size
Polylactic Acid-Polyglycolic Acid Copolymer
RNA Stability
RNA, Small Interfering analysis
RNA, Small Interfering genetics
Serum Albumin, Bovine chemistry
Sonication
Static Electricity
Surface Properties
Time Factors
Water chemistry
Drug Carriers chemistry
Lactic Acid chemistry
Nanoparticles chemistry
Polyglycolic Acid chemistry
RNA, Small Interfering administration & dosage
RNA, Small Interfering chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3476
- Volume :
- 390
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 19836438
- Full Text :
- https://doi.org/10.1016/j.ijpharm.2009.10.023