Water-dispersible oral, parenteral, and topical formulations for poorly water soluble drugs using smart polymeric nanoparticles

摘要

Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell areformed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of about 50%to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral;either water-soluble vinyl derivatives like vinylpyrolidone (VP) or vinylacetate (VA), or water insoluble vinyl derivatives like methyl methacrylate(MMA) or styrene (ST), at a molar ratio of about 10% to about 30%;, and acrylic acid(AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may beoptionally surface functional using reactive groups present in AA, includingPEGylation, or conjugation of moieties such as chemotherapeutics, contrastingagents, antibodies, radionucleides, ligands, and sugars, for diagnostic,therapeutic, and imaging purposes. The polymeric nanoparticles are preferablydispersed in aqueous solutions. The polymeric nanoparticles incorporate oneor more types of medicines or bioactive agents in the hydrophobic core; on occasion,the medicine or bioactive agent may be conjugated to the nanoparticle surfacevia reactive functional groups. The polymeric nanoparticles are capable ofdelivering the said medicines or bioactive agents through oral, parenteral,or topical routes. The polymeric nanoparticles allow poorly water soluble medicinesor bioactive agents, or those with poor oral bioavailability, to be formulatedin an aqueous solution, and enable their convenient delivery into the systemiccirculation.