Cationic materials and formulations for drug delivery
Cationic polymers are provided for delivering anionic active agents, preferably in the form or nanoparticles and other nanostructures. The polymer can be a polycation homopolymer or a copolymer containing a polycation block. The polycations and polycation containing polymers can contain dicarboxylic acid ester units and units of (α-amino acid)-α,ω-alkylene diester units. The nanoparticles can contain high loadings of anionic active agents, with sustained release of the active agents. Methods of making the polycations and polycation containing polymers are provided. Methods of making the nanoparticles and formulating them for administration to an individual in need thereof are also provided.
1. A method of providing sustained delivery of a therapeutic, prophylactic or diagnostic agent comprising administering to an individual in need thereof a population of non-aggregated particles, the particles comprising:
(a) one or more cationic polymer cores comprising a block copolymer comprising a polycation block and a biodegradable polymer block; and
(b) a shell layer of anionic therapeutic, prophylactic or diagnostic active agent encapsulating the one or more cationic polymer cores,
wherein the particles have a zeta potential between −10 mV and −30 mV.
2. The method of claim 1 , wherein the one or more cationic polymer cores has a diameter between 10 nm and 200 nm.
3. The method of claim 1 , wherein the particle is a multi-core shell nanoparticle and the nanoparticle comprises more than one cationic particle core.
4. The method of claim 1 , wherein the particle has a diameter of between 10 nm and 1,000 nm.
5. The method of claim 1 , wherein the particle comprises a protective layer and the anionic active agents are dispersed between the protective layer and the one or more cationic particle cores.
6. The method of claim 5 , wherein the protective layer is selected from the group consisting of lipid monolayers, lipid bilayers, biodegradable polymer layers, polymer-lipid conjugate layers, and combinations thereof.
7. The method of claim 1 , further comprising particles comprising cationic particle cores comprising the biodegradable polymer but not the polycation block.
8. The method of claim 1 , wherein the biodegradable polymer is selected from the group consisting of poly(lactic acid), poly(glycolic acid), and poly (lactic-co-glycolic acid).
9. The method of claim 1 , wherein the polycation block comprises a polymer comprising dicarboxylic acid ester units and units of (α-amino acid)-α,ω-alkylene diester units.
10. The method of claim 9 , wherein the polycation block comprises units having the structure
wherein R 1 is selected from the group consisting of linear and branched alkyl and substituted alkyl, alkenyl, or alkylene oxide groups containing from 2 to 20 carbon atoms;
wherein R 2 is selected from the group consisting of aliphatic amines, cycloaliphatic amines, heterocyclic amines, and aromatic amines containing from 1 to 12 carbon atoms; and
wherein n is an integer between 1 and 1,000.
11. The method of claim 10 , wherein one or both R 2 is the side chain of a cationic amino acid selected from the group consisting of lysine, arginine, histidine, homolysine, ornithine, diaminobutyric acid, diaminopimelic acid, diaminopropionic acid, homoarginine, trimethyllysine, trimethylornithine, 4-aminopiperidine-4- carboxylic acid, 4-amino-1-carbamimidoylpiperidine-4-carboxylic acid and 4-guanidinophenylalanine.
12. The method of claim 1 , wherein one or more of the cationic polymer cores comprise an inorganic particle and the cationic polymer block is on the surface of the inorganic particle.
13. The method of claim 12 , wherein the inorganic particle comprises a particle selected from the group consisting of gold particles, iron oxide particles, and silica particles.
14. The method of claim 1 , wherein the therapeutic or prophylactic agent is a protein.
15. The method of claim 1 , wherein the therapeutic or prophylactic agent is a nucleic acid molecule.
16. The method of claim 1 , wherein the particles are administered parenterally, enterally, pulmonarily, or topically.