PMID- 10684538
OWN - NLM
STAT- Publisher
LR  - 20191120
IS  - 1940-4034 (Electronic)
IS  - 1074-2484 (Linking)
VI  - 4
IP  - 3
DP  - 1999 Jul
TI  - Sustained Intramural Retention and Regional Redistribution Following Local 
      Vascular Delivery of Polylactic-Coglycolic Acid and Liposomal Nanoparticulate 
      Formulations Containing Probucol.
PG  - 167-174
AB  - BACKGROUND: Probucol reduces restenosis after angioplasty, provided oral 
      administration is begun 1 month before the procedure. Local vascular delivery of 
      a nonoparticulate formulation of probucol may obviate the need for drug loading 
      by acutely raising arterial intramural concentration while providing sustained 
      intramural retention. To test this hypothesis, we compared the retention and 
      redistribution of (35)S-probucol encapsulated in either liposomal or 
      polylactic-coglycolic acid (PLGA) nanoparticles after local vascular delivery. 
      METHODS: Nanoparticles were delivered using a Crescendo microporous infusion 
      catheter (Cordis, Warren, NJ) after balloon angioplasty of rabbit iliac arteries 
      (n = 12-18 arteries per formulation per time point). Animals were euthanized on 
      day 0, 3, or 7 after delivery. Iliac arteries, perivascular fat, and downstream 
      tissues were harvested and the radioactivity disintegrations per minute was 
      measured. Autoradiographic and confocal microscopic analyses of tissue sections 
      were performed to evaluate intramural distribution of probucol. RESULTS: 
      Immediately after delivery, radioactivity in the iliac arteries (log[dpm/mg], 
      mean +/- SEM) was greater with PLGA (2.72 +/- 0.08) than with liposomal 
      encapsulation (2.10 +/- 0.08, P = 0.001). Intramural retention of probucol was 
      23% at 7 days using liposomes and 10% using PLGA, corresponding to a probucol 
      concentration of 0.1 ng/mg tissue for both formulations. By the third day after 
      delivery, radioactivity in peri-iliac fat, femoral arteries, and hindlimb muscle 
      increased by 88%, 29%, and 154%, respectively. Thereafter, radioactivity 
      decreased to 56%, 43%, and 134% of initial dpm respectively, by day 7. 
      CONCLUSIONS: although delivery efficiency was superior with PLGA encapsulation, 
      intramural probucol concentrations were similar on day 7 using both formulations. 
      Radial and axial redistribution of probucol was observed, indicating that this 
      technique can be exploited to increase adjacent tissue delivery.
FAU - Klugherz, BD
AU  - Klugherz BD
AD  - University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA
FAU - Meneveau, N
AU  - Meneveau N
FAU - Chen, W
AU  - Chen W
FAU - Wade-Whittaker, F
AU  - Wade-Whittaker F
FAU - Papandreou, G
AU  - Papandreou G
FAU - Levy, R
AU  - Levy R
FAU - Wilensky, RL
AU  - Wilensky RL
LA  - eng
PT  - Journal Article
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol Ther
JT  - Journal of cardiovascular pharmacology and therapeutics
JID - 9602617
EDAT- 2000/02/23 00:00
MHDA- 2000/02/23 00:00
CRDT- 2000/02/23 00:00
PHST- 2000/02/23 00:00 [pubmed]
PHST- 2000/02/23 00:00 [medline]
PHST- 2000/02/23 00:00 [entrez]
AID - S107424849900019X [pii]
AID - 10.1177/107424849900400306 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol Ther. 1999 Jul;4(3):167-174. doi: 
      10.1177/107424849900400306.