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PLA‐PEG Nanospheres: New Carriers For Transmucosal Delivery Of Proteins And Plasmid DNA

A. Vila, A. Sánchez, Celso Pérez, M. Alonso
Published 2002 · Materials Science

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There is little doubt that advances in polymer synthesis and in the design of delivery systems will have a profound impact on future therapeutics and immunization practices based on complex molecules such as proteins and plasmids. Our approach in this area has been the design of nanoparticles made of poly(lactic acid)-poly(ethyleneglycol) (PLA-PEG), for mucosal delivery of proteins and plasmid DNA. The technologies for the formation of these nanoparticles, were conveniently adapted in order to encapsulate proteins efficiently (i.e., tetanus toxoid) and DNA (i.e., pCMV-βGal) into a PLA core coated by PEG. These techniques include the w/o/w emulsion–solvent evaporation technique and the w/o emulsion–solvent diffusion technique, both providing high protein/DNA loadings. Results showed that the presence of a PEG coating around the nanoparticles significantly enhanced their stability in the gastrointestinal fluids, as well as in contact with mucus enzymes. This coating was also found to be responsible for the enhanced transport of 125I-radiolabelled tetanus toxoid and its delivery to the blood circulation and the lymph nodes, following nasal administration to rats. Additionally, fluorescent microscopy studies aimed at examining the interaction and transport of the nanoparticles through the nasal mucosa demonstrated that these nanoparticles can, indeed, cross the nasal epithelium. Finally, the efficacy of these PEG-coated nanoparticles as nasal vaccine delivery vehicles was shown in vivo. More specifically, the tetanus toxoid-loaded nanoparticles were able to elicit enhanced and long-lasting immunogenic responses following nasal administration. On the other hand, a single dose of encapsulated DNA administered intranasally led to a significant systemic antibody response to the encoded protein, confirming that plasmid DNA can be encapsulated in PLA-PEG nanoparticles with significant retention of biological function. To summarize, the data reported in the present paper provide evidence of the potential of PLA-PEG nanoparticles as carriers for the transport of proteins and DNA across mucosal surfaces. Copyright © 2003 John Wiley & Sons, Ltd.
This paper references
10.1016/S0927-7765(99)00157-5
The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration.
Tobío (2000)
10.1002/(SICI)1097-4636(199810)42:1<45::AID-JBM7>3.0.CO;2-O
Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization.
P. Quellec (1998)
10.1016/S0168-3659(01)00397-2
Poly(lactic acid)-poly(ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA.
C. Pérez (2001)
10.1023/A:1011063232257
Tetanus Toxoid Loaded Nanoparticles from Sulfobutylated Poly(Vinyl Alcohol)-Graft-Poly(Lactide-co-Glycolide): Evaluation of Antibody Response After Oral and Nasal Application in Mice
T. Jung (2004)
10.1016/0169-409X(95)00025-3
Long circulating microparticulate drug carriers
S. Stolnik (1995)
10.1023/A:1011922819926
Stealth PLA-PEG Nanoparticles as Protein Carriers for Nasal Administration
M. Tobío (2004)
10.1023/A:1016039330870
Polyvinyl Derivatives as Novel Interactive Polymers for Controlled Gene Delivery to Muscle
R. Mumper (2004)
10.1016/S0264-410X(99)00313-8
Improved immunogenicity of a core-coated tetanus toxoid delivery system.
M. Tobío (1999)
10.1002/(SICI)1097-4636(19991205)47:3<388::AID-JBM14>3.0.CO;2-V
Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II. Controlled release properties.
P. Quellec (1999)
10.1016/S0939-6411(96)00013-6
Aqueous pseudolatex of zein for film coating of solid dosage forms
P. B. O'donnell (1997)
10.1016/S0939-6411(97)00056-8
Development and characterization of protein-loaded poly(lactide-co-glycolide) nanospheres
M. D. Blanco (1997)
10.1016/0169-409X(95)00026-4
The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres.
R. Gref (1995)
10.1016/S0939-6411(00)00143-0
Development and characterization of CyA-loaded poly(lactic acid)-poly(ethylene glycol)PEG micro- and nanoparticles. Comparison with conventional PLA particulate carriers.
R. Gref (2001)
10.1126/SCIENCE.8128245
Biodegradable long-circulating polymeric nanospheres.
R. Gref (1994)
10.1080/026520499289338
Comparative degradation study of biodegradable microspheres of poly(DL-lactide-co-glycolide) with poly(ethyleneglycol) derivates.
J. García (1999)
10.1016/0169-409X(95)00022-Y
Which polymers can make nanoparticulate drug carriers long-circulating?
V. Torchilin (1995)
10.1016/S0168-3659(97)00215-0
Protective interactive noncondensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle.
R. Mumper (1998)



This paper is referenced by
10.1016/J.JCONREL.2006.03.017
PLGA:poloxamer and PLGA:poloxamine blend nanostructures as carriers for nasal gene delivery.
N. Csaba (2006)
10.1517/17425247.3.4.463
The performance of nanocarriers for transmucosal drug delivery
N. Csaba (2006)
10.3724/SP.J.1105.2009.00097
BIODEGRADABLE POLYMERS FOR CONTROLLED RELEASE OF GENE DELIVERY SYSTEMS: BIODEGRADABLE POLYMERS FOR CONTROLLED RELEASE OF GENE DELIVERY SYSTEMS
Huili Fu (2009)
Microencapsulación de nanopartículas de quitosano para la administración pulmonar de macromoléculas terapéuticas
A. Grenha (2011)
Desarrollo de nuevos vehículos para la administración de vacunas genéticas
N. Csaba (2005)
10.2217/17435889.2.4.483
Use of degradable and nondegradable nanomaterials for controlled release.
W. Wan (2007)
10.1016/j.addr.2008.09.005
Nanoparticles for nasal vaccination.
N. Csaba (2009)
10.1016/J.EJPB.2003.09.006
Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice.
A. Vila (2004)
10.1016/J.IJPHARM.2007.08.022
Tyrosine-derived nanospheres for enhanced topical skin penetration.
L. Sheihet (2008)
Investigation of functionalized carbon nanotubes as a delivery system for enhanced gene expression with implications in developing DNA vaccines for hepatitis C virus
W. Chen (2008)
10.1016/J.JCONREL.2004.04.026
Transport of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density.
A. Vila (2004)
10.1002/PI.2173
Formation of honeycomb films from poly(L‐lactide)‐block‐poly(ethylene glycol) via water‐droplet templating
Ye Tian (2007)
10.1002/jps.22019
Effect of encapsulating arginine containing molecules on PLGA: a solid-state NMR study.
Jean-Baptiste Guilbaud (2010)
10.1080/10611860600721051
The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats
Q. Zhang (2006)
10.1016/S1773-2247(10)50044-3
From single-dose vaccine delivery systems to nanovaccines
Sara Vicente (2010)
10.1186/s12917-015-0481-y
Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves
Fawad Mansoor (2015)
10.1016/j.nano.2012.06.001
Polymeric nanogels as vaccine delivery systems.
S. A. Ferreira (2013)
10.2174/157341311794653541
Nanocarriers for Transmucosal Vaccine Delivery
S. Jain (2011)
10.1101/pdb.prot5468
Preparation of poly(lactic acid) (PLA) and poly(ethylene oxide) (PEO) nanoparticles as carriers for gene delivery.
N. Csaba (2010)
Synthesis of polymeric nanoparticles for the controlled release of hydrophobic and hydrophillic therapeutic compounds
Jiang Xu (2016)
10.1016/j.micpath.2020.104061
Comparison of immune responses in guinea pigs by intranasal delivery with different nanoparticles-loaded FMDV DNA vaccine.
H. Zheng (2020)
10.1517/17425247.2.2.205
Bioadhesive properties of pegylated nanoparticles
K. Yoncheva (2005)
10.2217/17435889.3.6.845
Nanoparticles as protein and gene carriers to mucosal surfaces.
M. de la Fuente (2008)
Structural Control of Monodisperse Polylactide Microspheres by Microfluidic Emulsification and Solvent Diffusion
Takaichi Watanabe (2014)
10.1201/9781420004137.CH3
Pharmaceutical Excipient Development—A Preclinical Challenge
P. Baldrick (2006)
10.3390/PR7060331
Development of Hydrophilic Drug Encapsulation and Controlled Release Using a Modified Nanoprecipitation Method
J. Xu (2019)
10.1016/J.PROGPOLYMSCI.2007.05.007
Polymer systems for gene delivery - Past, present, and future
S. Y. Wong (2007)
10.1002/mabi.201400488
Three-Layered Biodegradable Micelles Prepared by Two-Step Self-Assembly of PLA-PEI-PLA and PLA-PEG-PLA Triblock Copolymers as Efficient Gene Delivery System.
Daniel G. Abebe (2015)
10.1201/9781420008449.CH20
Nanoparticles as Adjuvant-Vectors for Vaccination
S. Espuelas (2007)
Nanoparticulate Drug Delivery Systems
Jaya Raja Kumar Kalaimani (2016)
10.1039/C1SM05910F
Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion
Takaichi Watanabe (2011)
10.1016/J.JCONREL.2004.07.030
Transmucosal macromolecular drug delivery.
C. Prego (2005)
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