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 mum, the abdomen of hairless rats using the Helios(TM) gene gun system (Helios(TM) 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 mum 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(TM) gun system is a very useful tool for delivering a variety of drugs in powder form into the skin and systemic circulation.