[Rapamycin-loaded poly (lactic-co-glycolic) acid nanoparticles for intraarterial local drug delivery: preparation, characterization, and in vitro/in vivo release].
OBJECTIVE
To sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.


METHODS
Rapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.


RESULTS
Biodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.


CONCLUSIONS
PLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.
Miao
Li-fu
LF
Heart Center, First Hospital of Tsinghua University, Beijing 100016, China. miaolifu@hotmail.com
Yang
Jing
J
Huang
Chao-lian
CL
Song
Cun-xian
CX
Zeng
Yu-jie
YJ
Chen
Lian-feng
LF
Zhu
Wen-ling
WL
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D007261:Infusions, Intra-Arterial; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013552:Swine; D013556:Swine, Miniature
D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020123:Sirolimus