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eration PAMAM dendrimers are cheaper, easier serum containing media increases the potential
to synthesize, less toxic and have longer circula- for translational applications in vivo.
DOI 10.1002/jps JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 99, NO. 1, JANUARY 2010
382 INTRA AND SALEM
CONCLUSIONS 3. O Hagan DT, Singh M, Ulmer JB. 2004. Micropar-
ticles for the delivery of DNA vaccines. Immunol
Rev 199:191 200.
PLGA particles have significant potential for
4. Zhang XQ, Intra J, Salem AK. 2008. Comparative
generating sustained transgene expression. Load-
study of poly(lactic-co-glycolic acid)-poly ethylenei-
ing pDNA into the PLGA microparticles generates
mine-plasmid DNA microparticles prepared using
nonviral vectors with poor transfection efficien-
double emulsion methods. J Microencapsul 25:1
cies. Cationic polymers such as PAMAM dendri-
12.
mer can generate high but transient transgene
5. Walter E, Moelling K, Pavlovic J, Merkle HP. 1999.
expression. However, higher generation PAMAM
Microencapsulation of DNA using poly(DL-lactide-
dendrimers alone are toxic and all PAMAM
co-glycolide): Stability issues and release character-
dendrimers display reduced transfection efficien-
istics. J Control Release 61:361 374.
cies in the presence of serum. Loading PAMAM 6. Tinsley-Bown AM, Fretwell R, Dowsett AB, Davis
SL, Farrar GH. 2000. Formulation of poly(D,L-lac-
pDNA dendriplexes into PLGA microparticles
tic-co-glycolic acid) microparticles for rapid plasmid
generates a delivery system that has several
DNA delivery. J Control Release 66:229 241.
advantages over either PLGA microparticles
7. Kasturi SP, Qin H, Thomson KS, El-Bereir S, Cha
alone or PAMAM dendrimers alone. PLGA
SC, Neelapu S, Kwak LW, Roy K. 2006. Prophylac-
microparticles loaded with PAMAM pDNA den-
tic anti-tumor effects in a B cell lymphoma model
driplexes have desirable cytotoxicity profiles
with DNA vaccines delivered on polyethylenimine
similar to PLGA microparticles alone, have higher
(PEI) functionalized PLGA microparticles.
cell uptake than PLGA microparticles alone,
J Control Release 113:261 270.
provide sustained release of PAMAM pDNA
8. Kasturi SP, Sachaphibulkij K, Roy K. 2005. Cova-
dendriplexes, have higher loading efficiencies of
lent conjugation of polyethyleneimine on biodegrad-
pDNA and generate strong transfection efficien- able microparticles for delivery of plasmid DNA
vaccines. Biomaterials 26:6375 6385.
cies in serum free or serum containing media.
9. Manuel WS, Zheng J, Hornsby PJ. 2001. Transfec-
PLGA microparticles loaded with PAMAM pDNA
tion by polyethyleneimine-coated microspheres.
dendriplexes are therefore likely to have signifi-
J Drug Target 9:15-þ.
cant translational potential for applications in
10. Singh M, Briones M, Ott G, O Hagan D. 2000.
RNA, DNA, and oligonucleotide delivery.
Cationic microparticles: A potent delivery system
for DNA vaccines. Proc Natl Acad Sci USA 97:811
816.
ACKNOWLEDGMENTS 11. Zhang XQ, Intra J, Salem AK. 2007. Conjugation of
polyamidoamine dendrimers on biodegradable
microparticles for nonviral gene delivery. Bioconjug
We gratefully acknowledge support from the
Chem 18:2068 2076.
American Cancer Society (RSG-09-015-01-CDD),
12. Sutton D, Durand R, Shuai XT, Gao JM. 2006.
the National Cancer Institute at the National
Poly(D,L-lactide-co-glycolide)/poly(ethylenimine)
Institutes of Health (1R21CA13345-01/
blend matrix system for pH sensitive drug delivery.
1R21CA128414-01A2), and the Pharmaceutical
J Appl Polym Sci 100:89 96.
Research and Manufacturers of America Founda-
13. Oster CG, Kissel T. 2005. Comparative study of
tion. J. Intra acknowledges support from the Par-
DNA encapsulation into PLGA microparticles using
enteral Drug Association for a predoctoral
modified double emulsion methods and spray dry-
fellowship.
ing techniques. J Microencapsul 22:235 244.
14. Yun YH, Jiang HL, Chan R, Chen WL. 2005. Sus-
tained release of PEG-g-chitosan complexed DNA
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