PMID- 18661542
OWN - NLM
STAT- MEDLINE
DCOM- 20090408
LR  - 20220409
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 98
IP  - 3
DP  - 2009 Mar
TI  - Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via 
      transient formation of microaggregates.
PG  - 970-84
LID - 10.1002/jps.21487 [doi]
AB  - Chitosan-modified paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) 
      nanoparticles with a mean diameter of 200-300 nm in distilled water were prepared 
      by a solvent evaporation method. The mean diameter increased dramatically in 
      contact with the mouse (CDF(1)) plasma, as a function of chitosan concentration 
      in the modification solution (e.g., 2670.5 nm for 0.7% chitosan-modified 
      nanoparticles, NP(3)), but reverted to almost its original size (i.e., 350.7 nm 
      for NP(3)) following 5 min of gentle agitation. The zeta potential of PLGA 
      nanoparticles was changed to positive by the chitosan modification. The in vitro 
      uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell 
      line (A549) were significantly increased by the modification. Most importantly, a 
      lung-specific increase in the distribution index of paclitaxel (i.e., 
      AUC(lung)/AUC(plasma)) was observed for chitosan-modified nanoparticles (e.g., 
      99.9 for NP(3) vs. 5.4 for Taxol) when nanoparticles were administered to 
      lung-metastasized mice via the tail vein at a paclitaxel dose of 10 mg/kg. 
      Transient formation of aggregates in the blood stream followed by enhanced 
      trapping in the lung capillaries, and electrical interaction-mediated enhanced 
      uptake across the endothelial cells of the lung tumor capillary appear to be 
      responsible for the lung-tumor-specific distribution of the chitosan modified 
      nanoparticles.
CI  - (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association
FAU - Yang, Rui
AU  - Yang R
AD  - National Research Laboratory for Transporters Targeted Drug Design, College of 
      Pharmacy, Seoul National University, Seoul 151-742, Korea.
FAU - Yang, Su-Geun
AU  - Yang SG
FAU - Shim, Won-Sik
AU  - Shim WS
FAU - Cui, Fude
AU  - Cui F
FAU - Cheng, Gang
AU  - Cheng G
FAU - Kim, In-Wha
AU  - Kim IW
FAU - Kim, Dae-Duk
AU  - Kim DD
FAU - Chung, Suk-Jae
AU  - Chung SJ
FAU - Shim, Chang-Koo
AU  - Shim CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Coumarins)
RN  - 0 (Thiazoles)
RN  - 0 (coumarin 6)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 9012-76-4 (Chitosan)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*administration & 
      dosage/blood/*pharmacokinetics/toxicity
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chitosan/chemistry
MH  - Coumarins/pharmacokinetics
MH  - Lactic Acid/chemistry
MH  - Lung/*metabolism
MH  - Lung Neoplasms/drug therapy
MH  - Male
MH  - Mice
MH  - Nanoparticles/*administration & dosage/chemistry/toxicity/ultrastructure
MH  - Paclitaxel/*administration & dosage/blood/*pharmacokinetics/toxicity
MH  - Particle Size
MH  - Polyglycolic Acid/chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Surface Properties
MH  - Thiazoles/pharmacokinetics
EDAT- 2008/07/29 09:00
MHDA- 2009/04/09 09:00
CRDT- 2008/07/29 09:00
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2009/04/09 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
AID - S0022-3549(16)32894-5 [pii]
AID - 10.1002/jps.21487 [doi]
PST - ppublish
SO  - J Pharm Sci. 2009 Mar;98(3):970-84. doi: 10.1002/jps.21487.