Abstract: Described are new biodegradable nanoparticle platforms for encapsulation and sustained release of protein therapeutics through a scalable and reproducible method. Specifically nanoparticles comprising a complex comprising a protein, or peptide, and a counter ion polymer are described.

Abstract: Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure wherein each R1 is independently an organic or hetero-organic group, each R2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Abstract: Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure wherein each R1 is independently an organic or hetero-organic group, each R2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Abstract: Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure wherein each R1 is independently an organic or hetero-organic group, each R2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Abstract: Amphiphilic block copolymers (BCPs) were prepared comprising a poly(ethylene oxide) block and a biodegradable polycarbonate block functionalized with disulfide groups and carboxylic acid groups. The BCPs form self-assembled micellar particles in aqueous solution that can be loaded with hydrophobic drugs for therapeutic drug delivery. The loaded particles have small particle sizes (<100 nm), narrow particle size distributions, and high drug loading capacity (up to about 50 wt %) based on total dry weight of the loaded particles. Particles loaded with DOX released the DOX in response to changes in pH and glutathione (GSH) redox chemistry. The loaded particles efficiently delivered and released DOX within tumor cells, effectively suppressing growth of the tumor cells at a similar or even lower drug concentration than free DOX. Blank particles containing no DOX did not induce cytotoxicity to cells.

Abstract: Amphiphilic block copolymers (BCPs) were prepared comprising a poly(ethylene oxide) block and a biodegradable polycarbonate block functionalized with disulfide groups and carboxylic acid groups. The BCPs form self-assembled micellar particles in aqueous solution that can be loaded with hydrophobic drugs for therapeutic drug delivery. The loaded particles have small particle sizes (<100 nm), narrow particle size distributions, and high drug loading capacity (up to about 50 wt %) based on total dry weight of the loaded particles. Particles loaded with DOX released the DOX in response to changes in pH and glutathione (GSH) redox chemistry. The loaded particles efficiently delivered and released DOX within tumor cells, effectively suppressing growth of the tumor cells at a similar or even lower drug concentration than free DOX. Blank particles containing no DOX did not induce cytotoxicity to cells.

Abstract: Nanoparticles comprise a drug, a first block polymer and a second block polymer. The first block polymer has a poly(ethylene oxide) (PEO) block and a polycarbonate block bearing a side chain aromatic nitrogen-containing heterocycle (N-heterocycle). The N-heterocycle can be in the form of a base, a hydrosalt of the base, a sulfobetaine adduct of the base, or a combination thereof. The second block polymer has a PEO block and a polycarbonate block bearing a side chain catechol group, which can be present as a catechol, oxidized form of a catechol, and/or a polymerized form of a catechol. The nanoparticles can be dispersed in water and are capable of controlled release of the drug.

Abstract: Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure wherein each R1 is independently an organic or hetero-organic group, each R2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

Abstract: Water soluble biodegradable polymers were prepared by an organoacid catalyzed ring opening polymerization (ROP) of a cyclic carbonate monomer bearing an active ester side chain. The initial polymer comprising an active ester side chain was treated with an amino-alcohol, which transformed the active ester groups to N-substituted amide groups bearing mono-hydroxy alkyl groups and/or dihydroxy alkyl groups, thereby forming the water soluble polymers. The water-soluble polymers are non-toxic and exhibit stealth properties in buffered serum solution.

Abstract: Water soluble biodegradable polymers were prepared by an organoacid catalyzed ring opening polymerization (ROP) of a cyclic carbonate monomer bearing an active ester side chain. The initial polymer comprising an active ester side chain was treated with an amino-alcohol, which transformed the active ester groups to N-substituted amide groups bearing mono-hydroxy alkyl groups and/or dihydroxy alkyl groups, thereby forming the water soluble polymers. The water-soluble polymers are non-toxic and exhibit stealth properties in buffered serum solution.

Abstract: Nanoparticles comprise a drug, a first block polymer and a second block polymer. The first block polymer has a poly(ethylene oxide) (PEO) block and a polycarbonate block bearing a side chain aromatic nitrogen-containing heterocycle (N-heterocycle). The N-heterocycle can be in the form of a base, a hydrosalt of the base, a sulfobetaine adduct of the base, or a combination thereof. The second block polymer has a PEO block and a polycarbonate block bearing a side chain catechol group, which can be present as a catechol, oxidized form of a catechol, and/or a polymerized form of a catechol. The nanoparticles can be dispersed in water and are capable of controlled release of the drug.