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High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.
- Source :
-
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2011 Jan; Vol. 77 (1), pp. 26-35. Date of Electronic Publication: 2010 Nov 18. - Publication Year :
- 2011
-
Abstract
- Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Acetylation
Cell Line
Chemical Phenomena
Delayed-Action Preparations administration & dosage
Delayed-Action Preparations chemistry
Delayed-Action Preparations pharmacology
Drug Carriers pharmacology
Drug Compounding
Drug Stability
Emulsions
Excipients chemistry
Gene Silencing drug effects
Humans
Nanoparticles ultrastructure
Nanotechnology
Particle Size
Polylactic Acid-Polyglycolic Acid Copolymer
RNA, Small Interfering chemistry
RNA, Small Interfering pharmacology
Serum Albumin, Bovine chemistry
Solubility
Surface Properties
Viscosity
Drug Carriers administration & dosage
Drug Carriers chemistry
Lactic Acid chemistry
Nanoparticles chemistry
Polyglycolic Acid chemistry
RNA, Small Interfering administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3441
- Volume :
- 77
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
- Publication Type :
- Academic Journal
- Accession number :
- 21093589
- Full Text :
- https://doi.org/10.1016/j.ejpb.2010.11.008