pharmaceutical ingredient is mastoporan 7, the ion pairing reagent is sodium dodecyl sulfate (SDS), and the nanopar› ticle encapsulation material is polycaprolactone-block-poly› ethylene glycol block copolymer. In an embodiment the active pharmaceutical ingredient is sub5, the ion pairing reagent is sodium dodecyl sulfate (SD S), and the nanopar› ticle encapsulation material is polycaprolactone-block-poly› ethylene glycol block copolymer. In an embodiment, the active pharmaceutical ingredient is LL37, the ion pairing reagent is sodium dodecyl sulfate (SDS), and the nanopar› ticle encapsulation material is polycaprolactone-block-poly› ethylene glycol block copolymer. In an embodiment, the active pharmaceutical ingredient is colistin, the ion pairing reagent is sodium oleate, and the nanoparticle encapsulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceu› tical ingredient is ecumicin, the ion pairing reagent is vitamin E succinate, and the nanoparticle encapsulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceu› tical ingredient is OZ439, the ion pairing reagent is sodium oleate, and the nanoparticle encapsulation material is hydroxypropyl methylcellulose acetate succinate (HPM› CAS). In an embodiment, the active pharmaceutical ingre› dient is ovalbumin, the ion pairing reagent is a quaternary ammonium surfactant, and the nanoparticle encapsulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceu› tical ingredient is ovalbumin, the ion pairing reagent is cetyl trimethylammonium bromide, and the nanoparticle encap› sulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceutical ingredient is lysozyme, the ion pairing reagent is sodium oleate, and the nanoparticle encapsulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceu› tical ingredient is lysozyme, the ion pairing reagent is sodium dodecyl sulfate (SDS), and the nanoparticle encap› sulation material is polycaprolactone-block-polyethylene glycol block copolymer. In an embodiment, the active pharmaceutical ingredient is lysozyme, the ion pairing reagent is dextran sulfate (DXS) polymer, and the nanopar› ticle encapsulation material is polycaprolactone-block-poly› ethylene glycol block copolymer. 

[0014] A method of the invention for encapsulating an active pharmaceutical ingredient (API) includes producing a hydrophobic salt by ion pairing charged functional groups on a water soluble API with an ion pairing (IP) reagent and forming nanoparticles that are carriers of the hydrophobic salt to encapsulate the API, with the IP reagent including a counterion for the APL Producing a hydrophobic salt can include mixing the API and the IP in water to form a water-insoluble precipitate as the hydrophobic salt, remov› ing the water, and dissolving the water-insoluble precipitate into an organic solvent. A polymer can be dissolved into the organic solvent. The organic solvent can be water-miscible. 

[0015] The dissolved water-insoluble precipitate can be used in an organic stream to form the nanoparticles by flash nanoprecipitation. 

[0016] The solution of the hydrophobic salt dissolved in the organic solvent can be continuously mixed with a polar solvent to form a mixed solution from which the nanopar› ticles assemble and precipitate. 

[0017] Producing a hydrophobic salt can include dissolv› ing the API in a water stream, dissolving the IP in an organic stream, and forming a water-insoluble precipitate as the hydrophobic salt through micro-mixing the organic stream against the water stream in a Flash NanoPrecipitation (FNP) process. A polymer can be dissolved into the organic stream. The organic stream can be water-miscible. 

[0018] The nanoparticles can be formed by dissolving the API in a polar solvent to form a polar solution stream, dissolving the IP in an organic solvent to form an organic solution stream, and continuously mixing the polar solution stream against the organic solution stream to form a mixed solution from which the nanoparticles that encapsulate the API assemble and precipitate, and the organic solvent can be less polar than the polar solvent. A polymer can be dissolved into the organic solvent. The organic solvent can be water› miscible. 

[0019] The nanoparticles can be formed by an emulsion/ stripping process. 

[0020] The API can be an antibacterial and/or a biologic. The API can be an antimicrobial small molecule, a peptide, a cationic peptide, an anionic peptide, a protein, a cationic protein, an anionic protein, or an aminoglycoside. The API can have an aqueous solubility of greater than 10 mg/ml, can have a log P value less than -2 in an aqueous solution at pH of 7, and/or can have 1, 2, 3, 4, 5, 6, or more ionic groups. The API can be other than an oligonucleotide. The API can be gentamycin, polymyxin B, mastoparan 7, sub5, LL37, colistin, ecumicin, OZ439, ovalbumin, or lysozyme. The API can be gentamycin, polymyxin B, mastoparan 7, sub5, colistin, or ovalbumin. 

[0021] The counterion can have a log P value of 2 or greater at a pH of 7. The counterion can have a log P value of greater than 5. The release profile of the API can exhibit a plateau in the release rate ( or fraction released) with time. The counterion can have 1, 2, or more ionic sites. The counterion can be an anionic counterion that has a pKa value of from -2 to 5. The counterion can have a pKb value of greater than 3. The counterion can be a quaternized cationic species, for example, a quaternized cationic species that is permanently cationic. The counterion can have an ionic site selected from the group consisting of a carboxylic acid, sulfate, sulfonate, or amine. The IP reagent can be sodium hexanoate, sodium decanoate, sodium myristate (MA), sodium oleate (OA), pamoic acid disodium salt (PA), ben› zenesulfonic acid monohydrate, sodium 2-naphthalenesul› fonate, (1 R)-(-)-10-camphorsulfonic acid, sodium 1,2-eth› anesulfonate, sodium 1-heptanesulfonate, sodium 1-octanesulfonate monohydrate, sodium 1-decanesulfonate, sodium dodecyl sulfate (SDS), sodium dodecylbenzene sul› fonate (DBS), sodium deoxycholate, or sodium decyl sulfate (DS). The counterion can be dodecyl hydrogen sulfate, decyl hydrogen sulfate, dodecylbenzene sulfonic acid, or myristic acid. The counterion can be oleic acid or pamoic acid. 

[0022] The polymer can be self-assembling. The polymer can be hydroxypropyl methylcellulose acetate succinate (HPMCAS), polystyrene-block-polyethylene glycol (PS-b› PEG), or polycaprolactone-block-polyethylene glycol (PCL-b-PEG). For example, the polymer can be 1.6 kDa polystyrene-block-5 kDa polyethylene glycol or 5 kDa poly› caprolactone-block-5 kDa polyethylene glycol. 

[0023] The nanoparticles can include a polyethylene gly› col coating. 

