Introduction of poly-L-lactic acid microspheres into the skin using supersonic flow: effects of helium gas pressure, particle size and microparticle dose on the amount introduced into hairless rat skin.
A microparticulate bombardment system loaded with DNA- and RNA-coated gold and tungsten microparticles (diameter 1-3 microm; density about 19 g cm(-3)), the Helios gene gun system (Helios gun system), has been used to deliver a gene into cells by accelerating the microparticles to high velocity using a supersonic flow of helium gas. To investigate whether drug-loaded microspheres, > 20 microm in diameter and about 1.0 g cm(-3) in density, could be delivered in powder form quantitatively into the skin using the Helios gun system equipped with a cartridge container fitted with a rupture membrane, we investigated the effect of the helium gas pressure in accelerating indometacin-loaded poly-L-lactic acid (PLA) microspheres, as well as the particle size and the bombardment dose on delivery into the skin. Introduction of indometacin (i.e. indometacin-loaded PLA microspheres) after bombardment, with 3.0 mg indometacin-loaded PLA microspheres of a particle size of 20-38, 44-53 and 75-100 microm at a helium pressure of 100, 200 and 300 psi, of the abdomen of hairless rats increased in parallel with the helium pressure and it was also affected by the particle size, being highest at a diameter of 75-100 microm. However, introduction of higher amounts of PLA microspheres resulted in more severe skin erythema (skin damage) as monitored by the Draize score. Using lower bombardment doses (0.5 and 1.0 mg), the efficiency of introduction was improved and the skin damage markedly reduced. Moreover, discrete bombardment with a low dose provided a more efficient introduction of indometacin and less skin damage. These results suggest that bombardment injection of drug-loaded microspheres in a powdered form by the Helios gun system appears to be a very useful tool for the quantitative delivery of a variety of drugs and an alternative to parenteral injection by needle, especially for delivering water-soluble macromolecules.
Uchida
Masaki
M
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Jin
Yi
Y
Natsume
Hideshi
H
Kobayashi
Daisuke
D
Sugibayashi
Kenji
K
Morimoto
Yasunori
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D001673:Biodegradation, Environmental; D004337:Drug Carriers; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006371:Helium; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D019344:Lactic Acid / Q000633:toxicity; D008297:Male; D018613:Microscopy, Confocal; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000633:toxicity; D011137:Polystyrenes; D011208:Powders; D011312:Pressure; D051381:Rats; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005456:Fluorescent Dyes; D011091:Polyesters; D011108:Polymers; D011137:Polystyrenes; D011208:Powders; D006371:Helium; D019344:Lactic Acid; C033616:poly(lactide); D016650:Fluorescein-5-isothiocyanate; D007213:Indomethacin