Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA
Abstract
The purpose of the present work was to produce and characterize poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) nanoparticles (size lower than 300 nm) containing a high loading of plasmid DNA in a free form or co-encapsulated with either poly(vinyl alcohol) (PVA) or poly(vinylpyrrolidone) (PVP). The plasmid alone or with PVA or PVP was encapsulated by two different techniques: an optimized w/o/w emulsion-solvent evaporation technique as well as by a new w/o emulsion-solvent diffusion technique. Particle size, zeta potential, plasmid DNA loading and in vitro release were determined for the three plasmid-loaded formulations. The influence of the initial plasmid loadings (5, 10, 20 microg plasmid DNA/mg PLA-PEG) on those parameters was also investigated. The plasmid loaded into the nanoparticles and released in vitro was quantified by fluorimetry and the different molecular forms were identified by gel electrophoresis. PLA-PEG nanoparticles containing plasmid DNA in a free form or co-encapsulated with PVA or PVP were obtained in the range size of 150-300 nm and with a negative zeta potential, both parameters being affected by the preparation technique. Encapsulation efficiencies were high irrespective of the presence of PVA or PVP (60-90%) and were slightly affected by the preparation technique and by the initial loading. The final plasmid DNA loading in the nanoparticles was up to 10-12 microg plasmid DNA/mg polymer. Plasmid DNA release kinetics varied depending on the plasmid incorporation technique: nanoparticles prepared by the w/o diffusion technique released their content rapidly whereas those obtained by the w/o/w showed an initial burst followed by a slow release for at least 28 days. No significant influence of the plasmid DNA loading and of the co-encapsulation of PVP or PVA on the in vitro release rate was observed. In all cases the conversion of the supercoiled form to the open circular and linear forms was detected. In conclusion, plasmid DNA can be very efficiently encapsulated, either in a free form or in combination with PVP and PVA, into PLA-PEG nanoparticles. Additionally, depending on the processing conditions, these nanoparticles release plasmid DNA either very rapidly or in a controlled manner.
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Polymeric nanoparticles can be formulated for encapsulation of various hydrophilic and hydrophobic smaller molecules, particularly drugs and macromolecules such as proteins or peptides.
“Polymeric nanoparticles can be formulated for the encapsulation of various hydrophilic and hydrophobic smaller molecules, particularly drugs and macromolecules such as proteins or peptides.232”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [232]
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- Authors
- Perez, C., Sanchez, A., Putnam, D., Ting, D., Langer, R., & Alonso, M. J.
- Affiliations
- Massachusetts Institute of Technology (US)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 75
- Issue
- 1-2
- Pages
- 211-224
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2056831300
- Cited by
- 313
- References
- 27
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 5 · 2022: 11 · 2021: 4 · 2020: 13 · 2019: 10 · 2018: 9 · 2017: 12 · 2016: 9 · 2015: 15 · 2014: 13 · 2013: 14 · 2012: 21
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- plasmid DNA delivery, gene delivery, polyvinyl alcohol, polyvinylpyrrolidone, encapsulation efficiency, controlled release, DNA supercoiling, nanoparticle size and zeta potential
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Chemistry, Physical, Diffusion, DNA, Drug Carriers, Drug Compounding, Emulsions, Excipients, Microspheres, Particle Size, Plasmids, Polyethylene Glycols, Polyglycolic Acid, Polymers, Polyvinyl Alcohol, Solvents, Genetic Therapy, Drug Delivery Systems, Lactic Acid, Chemical Phenomena
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