[Preparation of ASODN-protamine-HSA-PLGA nanoparticles and initial evaluation of their nucleus targeting property in vitro].
OBJECTIVE
To develop a novel non-viral gene delivery system-SODN-Protamine-HSA-PLGA (ASODN-P/H-PLGA-NP) and investigate its nucleus targeting potential in vitro.


METHODS
ASODN-P/H-PLGA-NP was prepared by mixing the protamine sulfate and HSA. Then the PLGA nanoparticles were prepared using double-emulsion evaporation technique, followed by addition of ASODN to the prepared P/H complex. The morphology of ASODN-P/H-PLGA-NP was observed by transmission electron microscopy. The diameter, PDI, and surface charge of ASODN-P/H-PLGA-NP were measured by photo correlation spectroscopy (PCS). The encapsulation efficiency of ASODN was determined by double step method. The cytotoxicity of ASODN-P/H-PLGA-NP was investigated by MTT assays. The ability to enter the squamouse carcinoma: Hep-2 cell line and its nucleus targeting property were observed by confocal laser scanning microscope.


RESULTS
The average diameter, PDI, zeta potential, and encapsulation efficiency of ASODN-P/H-PLGA-NP were 128 nm, 0.234, -23.3 mV, and 78.45%, respectively. ASODN-P/H-PLGA-NP could protect the ASODN from the shear force in the ultrasound process during preparation. ASODN-P/H-PLGA-NP couldenter Hep-2 cells and have certain level of nucleus targeting property.


CONCLUSIONS
ASODN-P/H-PLGA-NP can be prepared easily with small particle sizes and low cytotoxicity, which might be employed as a good non-viral vector for applications in ASODN delivery to nucleus.
Zhang
Yi
Y
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Yuan
Li
L
Yan
Xiao-ling
XL
Gong
Tao
T
Liu
Jie
J
Zhang
Zhi-rong
ZR
Sun
Xun
X
D002467:Cell Nucleus / Q000378:metabolism*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011479:Protamines / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*
D004337:Drug Carriers; D020319:Oligodeoxyribonucleotides, Antisense; D011479:Protamines; D012709:Serum Albumin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid