Abstract: Methods and systems and related devices particles and compositions are described for controlled ballistic delivery of particles to a target region of a multilayered tissue, the method comprising determining a velocity vo,j of the set of substantially spherical particles by iterating vo,i=?{square root over (Ya/?p)}((1/k)(d*/Dm)(?am-1)(?{square root over (Ya?p)})1-m(?a/?p))1/ni from i=0 to j, where n0=0.826 and ni=n0?q(v0,i-1?{square root over (?a/Ya)}), until |(v0,i?v0,i-1)/vo,i-1|<0.1; selecting the Dp, ?p and vo,j when vo,j is less than 1,500 m/sec; and ballistically delivering a set of substantially spherical therapeutic particles having the selected Dp and ?p at velocity vo,j to the accessible surface of the apical layer of the bilayer tissue to deliver into the target region at least 30% of the set of substantially spherical particles.