Ballistic delivery and related particles, compositions, methods and systems
Methods and systems and related particles and compositions that can be used to deliver a biologically active cargo such as a drug to a cornea of an individual, the delivery performed in a rapid, nonsurgical, and/or controllable fashion are described. Particularly, a method is described for controlled ballistic delivery of a cargo in a microparticle to the cornea of an individual, including a biologically active cargo.
1 . A method for controlled ballistic delivery of a biologically active cargo to the cornea of an individual comprising an epithelium layer and a stroma layer and an interface between the epithelium layer and the stroma layer, the method comprising
ballistically delivering to the cornea a convex microparticle comprising the biologically active cargo optionally in combination with a carrier material, the convex microparticle having a diameter from 5 to 30 μm and a density from 1 g/cc up to less than 20 g/cc,
the ballistically delivering performed at a velocity equal to or higher than 100 m/s to a set target region of the cornea from the epithelium layer to the stroma layer of the cornea of the individual
wherein the ballistic delivery is controlled by selecting the density of the convex microparticle to correspond to the set target region such that:
wherein when the convex microparticle has a density from 1.0 g/cc to 2.5 g/cc the set target region is a target region located within the epithelium of the cornea,
wherein when the convex microparticle has a density higher than 2.5 g/cc to 7.8 g/cc the set target region is a target region located in the epithelium layer, in the stroma layer of the cornea and/or within the interface between epithelium layer and stroma layer of the cornea, and
wherein when the convex microparticle has a density higher than 7.8 g/cc to less than 20 g/cc the set target region is a target region within the interface between the epithelium layer and the stroma layer of the cornea, or within the stroma layer of the cornea.
2 . The method of claim 1 , wherein the ballistically delivering is performed at a velocity of from 200 m/s to 500 m/s.
3 . The method of claim 1 , wherein the convex microparticle comprises a carrier material and the carrier material comprises a polymer, a glass, a metal and/or an alloy.
4 . The method of claim 1 , wherein the carrier material comprises a polymer of Formula (I):
in which
B 1 to B m each refers to a block polymer moiety which are copolymerized to form copolymer B 1 -co-B 2 . . . co-B m , wherein m ranges from 1 to 9,
b2 to bm each refers to a molar fractional number of block polymer moiety B2 to Bm relative to B1, wherein b2 to bm are each equal to or less than 1 and a sum of b2 to bm is equal to or less than 5,
X 1 to X p each refers to a cross-linker moiety, each of which cross-links at least two polymer moieties,
r1 to rp each refers a molar fractional number of cross-linker L 1 to L p per block copolymer [B 1 -co-(B 2 ) b2 . . . co-(B m ) bm ], wherein a sum of r1 to rp is equal to or less than 0.5, and
wherein the molecular weight of the carrier particle ranges from 5000 Daltons to 5,000,000 Daltons.
5 . The method of claim 4 , wherein the polymer of Formula (I) comprises poly-N-2-dimethylamino ethyl-methacrylamide (PDMAEMAm), poly-N-2-dimethylamino ethyl-acrylamide (PDMAEAAm), poly-N-2-dimethylamino ethyl-methacrylate (PDMAEMA), poly-N-2-dimethylamino ethyl-acrylate (PDMAEA), poly methacrylamide (PMAAm), poly N,N-dimethyl methacrylamide (PDMMAAm), polymethyl methacrylate (PMMA), polyacrylamide (PAAm), polyacrylic acid (PAA), poly dimethylaminoethylmethacrylate (PDEAEMA), polyisopropylacrylamide (PNIPAAm), poly(N-isopropyl-3-butenamide) (PNIPBAm), alpha-aminoomega-methyl-poly ethylene glycol (AMPEG), poly(epsilon-caprolactone-co-lactide-polyethylene glycol) copolymer, cross-linked copolymers of polyethyleneglycol and methyacrylic acid, block copolymer poly(methacrylic acid-co-ethylene glycol), block copolymer poly(2-hydroxythyl methacrylate-co-N,N-dimethylaminoethyl methacrylate), poly(hydroxyethyl methacrylamide) (poly-HEMAm), copolymer poly(HEMA-co-DMAEMA) poly(hydroxylethyl methacrylate-co-N,N-dimethylaminoethylmethacrylate), copolymer of gelatin and PVA (polyvinyl alcohol), co-polymer of poly-PNIPA and poly-PNIPA-Co-AA (poly N-isopropyl acrylamide and poly N-isopropyl acrylamide-co-acrylic acid), poly organophosphazene with a-amino omegamethylpolyethylene glycol, polyepsilon caprolactone-co-lactide-polyethylene glycol, poly(NIPAAm-co-AAm) (N-isopropylacryalmide-co-acryalmide), poly(methacrylamide-co-N-vinyl-2-pyrrolidone-co-itaconic acid), poly(2-(N-ethylperfluorooctanesulfonamido) ethylacrylate), a cross-linked polymer thereof or a cross-linked any combination of polymers thereof.
6 . The method of claim 1 , wherein the carrier material comprises a polymer of Formula (II):
wherein M is a monomeric moiety, n is the degree of polymerization ranging from 50 to 500,000, M is a monomeric moiety formed by a polymerized monomer.
7 . The method of claim 6 , wherein the polymer of Formula (II) comprises poly(N-vinylpyrrolidone), poly(acrylic acid), poly(methacrylic acid), poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylic acid), poly(2-hydroxypropyl methacrylate), poly(2-ethyl-2-oxazoline), polymethacrylamide, polyacrylamide, poly(N-iso-propylacrylamide), poly(2-vinylpyridine), poly(2-vinylpyridine N-oxide), poly(4-vinylpyridine), poly(4-vinylpyridine N-oxide), poly(2-vinyl-1-methylpyridinium bromide), poly(ethylene oxide), poly(propylene oxide), poly(styrenesulfonic acid), poly(styrenesulfonate sodium), poly(vinylsulfonic acid), poly(vinylsulfonate sodium), poly(vinyl phosphoric acid), poly(vinyl phosphorate sodium), poly(vinyl alcohol), poly(allyl amine), poly(2-methacryloxyethyltrimethylammonium bromide), poly(N-vinylpyrrolidone), poly(vinyl acetate) or any combinations thereof.
8 . The method of claim 1 , wherein the carrier material comprises a poly(ethylene glycol) (PEG), poly(D-lactic acid) (PDLA), poly(L-lactic acid) (PLLA), poly(D-lactic acid-co-L-lactic acid) (PDLLA) and poly(ethylene glycol), polyglycolic acid (PGA) or any combination thereof.
9 . The method of claim 1 , wherein the carrier material is carrier glass comprising any one of soda-lime glass, borosilicate glass, and an aluminosilicate glass.
10 . The method of claim 1 , wherein the carrier material is carrier metal from Group 3 to Group 12 elements and/or from metal elements in Group 13 to Group 14.
11 . The method of claim 10 , wherein the carrier material comprises any one of metal titanium, iron, copper, silver, gold, tungsten or a combination thereof.
12 . The method of claim 1 , wherein the carrier material is porous.
13 . The method of claim 1 , wherein the carrier material alloy comprising a metal of any one of Group 1 to Group 14.
14 . The method of claim 1 , wherein the carrier material is a porous carrier glass, a porous carrier metal and/or a porous carrier alloy.
15 . The method of claim 1 , wherein the cargo comprises a prostaglandin analog, a-adrenoreceptor agonist, B-adrenoreceptor antagonist, carbonic anhydrase inhibitor, and parasympathomimetic agents or any combination thereof.
16 . The method of claim 1 , wherein the cargo comprises an anti-angiogenic ophthalmic agent, a mydriatics, an anesthetic, an anti-infective agent, an antihistamine and/or decongestant, a glaucoma agent, a steroid or any combination thereof.
17 . The method of claim 1 , wherein the biologically active cargo comprises a photosensitizing agent capable of corneal cross-linking.
18 . The method of claim 1 , wherein the convex microparticle is a substantially spherical microparticle.