Effects of particle size, helium gas pressure and microparticle dose on the plasma concentration of indomethacin after bombardment of indomethacin-loaded poly-L-lactic acid microspheres using a Helios gun system.
We investigated the effects of the particle size of indomethacin-loaded poly-L-lactic acid microspheres (IDM-loaded PLA MS), the helium pressure used to accelerate the particles, and the bombardment dose of PLA MS on the plasma concentration of IDM after bombarding with IDM-loaded PLA MS of different particle size ranges, 20-38, 44-53 and 75-100 microm, the abdomen of hairless rats using the Helios gene gun system (Helios gun system). Using larger particles and a higher helium pressure, produced an increase in the plasma IDM concentration and the area under the plasma concentration-time curve (AUC) and resultant F (relative bioavailability with respect to intracutaneous injection) of IDM increased by an amount depending on the particle size and helium pressure. Although a reduction in the bombardment dose led to a decrease in C(max) and AUC, F increased on decreasing the bombardment dose. In addition, a more efficient F was obtained after bombarding with IDM-loaded PLA MS of 75-100 microm in diameter at each low dose in different sites of the abdomen compared with that after bolus bombardment with a high dose (dose equivalent). These results suggest that the bombardment injection of drug-loaded microspheres by the Helios gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.
Uchida
Masaki
M
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan..
Natsume
Hideshi
H
Kobayashi
Daisuke
D
Sugibayashi
Kenji
K
Morimoto
Yasunori
Y
D000399:Air Pressure; D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D006371:Helium; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000494:pharmacology; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000494:pharmacology; D051381:Rats; D012867:Skin / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011091:Polyesters; D011108:Polymers; D006371:Helium; D019344:Lactic Acid; C033616:poly(lactide); D007213:Indomethacin