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 making particles, comprising:
(a) obtaining a copolymer dissolved in a first solvent to yield a dissolved copolymer, the copolymer comprising a polycation and a biodegradable polymer; and
(b) generating particles from the dissolved copolymer, the particles comprising a cationic polymer core comprising the copolymer and an anionic active agent,
wherein the particles comprise a zeta potential less than −10 mV.
2. The method of claim 1 , wherein the anionic active agent comprises a therapeutic, prophylactic, or diagnostic agent.
3. The method of claim 1 , wherein the anionic active agent comprises a protein or nucleic acid.
4. The method of claim 1 , wherein the particles comprise a diameter between 10 nm and 200 nm.
5. The method of claim 1 , wherein the particles comprise a zeta potential greater than −30 mV.
6. The method of claim 1 , wherein the particles comprise the anionic active agent at an outside edge of the particle core.
7. The method of claim 1 , wherein the particles are not aggregated.
8. The method of claim 1 , wherein (a) comprises dissolving the copolymer in the first solvent to obtain a dissolved copolymer.
9. The method of claim 6 , further comprising combining the dissolved copolymer with a second solvent having a different hydrophobicity than the first solvent to generate the particles.
10. The method of claim 9 , wherein the second solvent is more hydrophobic than the first solvent.
11. The method of claim 9 , further comprising forming an emulsion comprising the first solvent and the second solvent.
12. The method of claim 1 , wherein the first solvent is a water immiscible solvent, and wherein generating the particles comprises combining the dissolved copolymer with an aqueous solution.
13. The method of claim 1 , wherein generating the particles comprises flowing the dissolved copolymer through a microfluidic channel that-combines the dissolved copolymer with a copolymer non-solvent to form the particles.
14. The method of claim 1 , wherein the particles have a homogeneous size distribution.
15. The method of claim 1 , wherein the copolymer comprises three or more different polymer blocks.
16. The method of claim 1 , wherein the copolymer comprises a conjugate selected from a targeting moiety, a lipid, a protective group, a reactive coupling group, a detectable label, or a therapeutic, prophylactic, or diagnostic agent.
17. The method of claim 1 , wherein the copolymer is a polyalkylene oxide-modified copolymer.
18. The method of claim 1 , wherein the first solvent comprises acetone, ethanol, methanol, isopropyl alcohol, acetonitrile or dimethyl sulfoxide.