title: A microarray MEMS device for biolistic delivery of vaccine and drug powders.
abstract: We report a biolistic technology platform for physical delivery of particle formulations of drugs or vaccines using parallel arrays of microchannels, which generate highly collimated jets of particles with high spatial resolution. Our approach allows for effective delivery of therapeutics sequentially or concurrently (in mixture) at a specified target location or treatment area. We show this new platform enables the delivery of a broad range of particles with various densities and sizes into both in vitro and ex vivo skin models. Penetration depths of ∼1 mm have been achieved following a single ejection of 200 µg high-density gold particles, as well as 13.6 µg low-density polystyrene-based particles into gelatin-based skin simulants at 70 psi inlet gas pressure. Ejection of multiple shots at one treatment site enabled deeper penetration of ∼3 mm in vitro, and delivery of a higher dose of 1 mg gold particles at similar inlet gas pressure. We demonstrate that particle penetration depths can be optimized in vitro by adjusting the inlet pressure of the carrier gas, and dosing is controlled by drug reservoirs that hold precise quantities of the payload, which can be ejected continuously or in pulses. Future investigations include comparison between continuous versus pulsatile payload deliveries. We have successfully delivered plasmid DNA (pDNA)-coated gold particles (1.15 µm diameter) into ex vivo murine and porcine skin at low inlet pressures of ∼30 psi. Integrity analysis of these pDNA-coated gold particles confirmed the preservation of full-length pDNA after each particle preparation and jetting procedures. This technology platform provides distinct capabilities to effectively deliver a broad range of particle formulations into skin with specially designed high-speed microarray ejector nozzles.
authors.affiliation: a Palo Alto Research Center Inc., (PARC) ; Palo Alto , CA USA.
authors.forename: Fatemeh Nazly
authors.initials: FN
authors.lastname: Pirmoradi
authors.forename: Ashish V
authors.initials: AV
authors.lastname: Pattekar
authors.forename: Felicia
authors.initials: F
authors.lastname: Linn
authors.forename: Michael I
authors.initials: MI
authors.lastname: Recht
authors.forename: Armin R
authors.initials: AR
authors.lastname: Volkel
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Greg B
authors.initials: GB
authors.lastname: Anderson
authors.forename: Mandana
authors.initials: M
authors.lastname: Veiseh
authors.forename: Sandra
authors.initials: S
authors.lastname: Kjono
authors.forename: Eric
authors.initials: E
authors.lastname: Peeters
authors.forename: Scott A
authors.initials: SA
authors.lastname: Uhland
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Chow
mesh_terms: D000818:Animals; D019470:Biolistics / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008807:Mice, Inbred BALB C; D055617:Micro-Electrical-Mechanical Systems / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011208:Powders / Q000008:administration & dosage*; D013552:Swine; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D019444:Vaccines, DNA
keywords: APC, Antigen Presenting Cells; CFD, Computational Fluid Dynamics; MEMS, MicroElectroMechanical System; biolistic; epidermal delivery; gene gun; injection microarrays; intracellular delivery; intradermal delivery; needle-free vaccine injection; pDNA, Plasmid DNA; particle collimation; particle ejection; transdermal drug delivery