PMID- 18188727
OWN - NLM
STAT- MEDLINE
DCOM- 20080502
LR  - 20191210
IS  - 0265-2048 (Print)
IS  - 0265-2048 (Linking)
VI  - 25
IP  - 1
DP  - 2008 Feb
TI  - Comparative study of poly (lactic-co-glycolic acid)-poly ethyleneimine-plasmid 
      DNA microparticles prepared using double emulsion methods.
PG  - 1-12
LID - 10.1080/02652040701659347 [doi]
AB  - Controlled release of plasmid DNA (pDNA) from biodegradable poly 
      lactic-co-glycolic acid (PLGA) microparticles has the potential to enhance 
      transgene expression. However, barriers to this approach include limited 
      encapsulation efficiency, pDNA damage during fabrication and confinement of the 
      microparticles inside phagolysosomal compartments. Combining PLGA with poly 
      ethyleneimine (PEI) can improve protection of pDNA during fabrication, increase 
      encapsulation efficiencies and impart the PLGA microparticles with the capacity 
      to escape the phagolysosomal compartments. This study compares three promising 
      formulation methods for preparing PLGA PEI pDNA microparticles and evaluates for 
      buffering capacity, cellular uptake, transfection efficiency and toxicity. In the 
      first method, PLGA PEI pDNA microparticles are prepared by entrapping pDNA in 
      blended PLGA/PEI using the double emulsion water-in-oil-in-water solvent 
      evaporation technique (PA). In a second approach, PEI-pDNA polyplexes are 
      prepared and then entrapped in PLGA microparticles using a double emulsion 
      solvent evaporation method (PB). Microparticles prepared using formulation 
      methods PA and PB are then compared against PLGA microparticles with PEI 
      conjugated to the surface using carbodiimide chemistry (PC); 0.5% PVA is 
      identified as the optimum concentration of surfactant for generating the 
      strongest transfection efficiencies. N:P ratios of 5 and 10 are selected for 
      preparation of each group. Gel electrophoresis demonstrates that all PLGA 
      microparticle formulations have strong pDNA binding capacity. An MTT assay shows 
      that in vitro cytotoxicity of PLGA PEI microparticles is significantly lower than 
      PEI alone. PLGA PEI pDNA microparticles mediate higher cellular uptake efficiency 
      and consequently higher transgene expression than unmodified PLGA microparticles 
      in COS7 and HEK293 cells. Preparing PEI-pDNA polyplexes prior to entrapment in 
      PLGA microparticles (PB) results in the highest pDNA loading. This is 2.5-fold 
      higher than pDNA loading in unmodified PLGA microparticles. PLGA PEI pDNA 
      microparticles prepared using method PB generates the strongest transfection 
      efficiencies, which are 500-fold higher than unmodified PLGA pDNA microparticles 
      in HEK293 cells and 1800-fold higher in COS-7 cells. The highest transfection 
      efficiencies generated from microparticles prepared using method PB is achieved 
      using an N:P ratio of 5.
FAU - Zhang, Xue-Qing
AU  - Zhang XQ
AD  - Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 
      52242, USA.
FAU - Intra, Janjira
AU  - Intra J
FAU - Salem, Aliasger K
AU  - Salem AK
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Microencapsul
JT  - Journal of microencapsulation
JID - 8500513
RN  - 0 (Coated Materials, Biocompatible)
RN  - 0 (Emulsions)
RN  - 0 (Polyesters)
RN  - 0 (Polymers)
RN  - 0 (Solvents)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 459TN2L5F5 (poly(lactide))
RN  - 9002-98-6 (Polyethyleneimine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - COS Cells
MH  - Cell Line
MH  - Chlorocebus aethiops
MH  - Coated Materials, Biocompatible/*chemistry
MH  - DNA/*administration & dosage/genetics
MH  - Drug Delivery Systems
MH  - Emulsions/chemistry
MH  - Lactic Acid/*chemistry
MH  - Microspheres
MH  - Particle Size
MH  - Plasmids/*chemistry/genetics
MH  - Polyesters
MH  - Polyethyleneimine/*chemistry
MH  - Polyglycolic Acid
MH  - Polymers/*chemistry
MH  - Solvents/chemistry
EDAT- 2008/01/12 09:00
MHDA- 2008/05/03 09:00
CRDT- 2008/01/12 09:00
PHST- 2008/01/12 09:00 [pubmed]
PHST- 2008/05/03 09:00 [medline]
PHST- 2008/01/12 09:00 [entrez]
AID - 783540301 [pii]
AID - 10.1080/02652040701659347 [doi]
PST - ppublish
SO  - J Microencapsul. 2008 Feb;25(1):1-12. doi: 10.1080/02652040701659347.