Hydrophobic drug nanoparticles have been prepared by ambient solvent evaporation from ethanol at room temperature. Poly(ethylene glycol)-b-(N-isopropylacrylamide) (PEG-b-PNIPAm) branched diblock copolymers are employed to prevent drug crystallization during solvent evaporation and to stabilize the drug nanoparticles once suspended in aqueous media. After the initial solvent evaporation the dry materials obtained exhibit excellent stability during storage and can be readily dissolved in water to produce aqueous drug nanoparticles suspensions. Among the hydrophobic compounds investigated, Ketoprofen nanoparticles (Dh ≈ 200 nm, stable up to 9 months in solution) can be produced with a drug suspension yield of 96% at a drug:polymer ratio of 0.33:1 or a drug suspension yield of 80% at a drug:polymer ratio of 1:1. UV–vis spectroscopy has been used to determine the yield of drug suspended in aqueous media while cryo-TEM, dynamic light scattering (DLS) and powder x-ray diffraction (PXRD) are used to characterize the drug nanoparticles prepared.Download high-res image (338KB)Download full-size image

Spherical unimolecular amphiphilic branched A-B block copolymer nanoparticles in methanol are fabricated via thermal annealing using the methanolic upper critical solution temperature (UCST) of the hydrophobic block segment. These polymer nanoparticles are then used to produce an aqueous poorly water-soluble drug nanoparticle suspension with a mass : drug ratio of 1 : 1 and 100% nanoparticle yield. The drug nanoparticles in the suspension are stabilized by multiple polymer nanoparticles.

A large percentage of drug compounds exhibit low water solubility and hence low bioavailability and therapeutic efficacy. This may be addressed by preparation of drug nanoparticles, leading to enhanced dissolution rate and direct use for treatment. Various methods have been developed to produce drug nanocrystals, including wet milling, homogenization, solution precipitation, emulsion diffusion, and the recently developed emulsion freeze-drying. The drawback for these methods may include difficult control in particles size, use of surfactants & polymer, and low ratio of drug to stabilizer. Here, biocompatible branched block copolymer nanoparticles with lightly-crosslinked hydrophobic core and hydrophilic surface groups are synthesized by the direct monomer-to-particle methodology, characterized, and then used as scaffold polymer/surfactant to produce drug nanoparticles via the emulsion-freeze-drying approach. This method can be used for model organic dye and different poorly water-soluble drugs. Aqueous drug nanoparticle dispersions can be obtained with high ratio of drug to stabilizer and relatively uniform nanoparticle sizes.

Spherical unimolecular amphiphilic branched A-B block copolymer nanoparticles in methanol are fabricated via thermal annealing using the methanolic upper critical solution temperature (UCST) of the hydrophobic block segment. These polymer nanoparticles are then used to produce an aqueous poorly water-soluble drug nanoparticle suspension with a mass:drug ratio of 1:1 and 100% nanoparticle yield. The drug nanoparticles in the suspension are stabilized by multiple polymer nanoparticles.