title: Single-step process to produce surface-functionalized polymeric nanoparticles.
abstract: Nanoparticles (NPs) are a versatile medium for the localization of therapeutics to tumors and for cellular and tissue imaging. The ability to impart targeting capability or enhance cellular uptake is dependent in part on the presentation of relevant surface functionality, among other design parameters. Currently, the production of functionalized polymeric NPs requires the a priori synthesis of polymers bearing such functionality. Here we describe a process to produce functionalized polymeric NPs derived from nonfunctional polymers in a single step. This was achieved by tailoring the solvation of the polymer using a binary solvent system such that the addition of an aqueous phase rich in water-soluble polymer or polyelectrolytes results in the formation of NPs with the concomitant functionalization of NP surfaces with the polymeric moieties introduced into the aqueous phase. This strategy also allows for easy control over NP size independent of surface functionality. We have demonstrated that poly(lactic-co-glycolic acid) (PLGA) NPs bearing surface functionality as diverse as biological polysaccharides such as heparin, water-soluble ionic polymers, and poly(ethylene glycol) can be prepared under identical conditions in a single step, with surface coverage (mass %) ranging from 3 to >70%. We expect this novel process to enable complex surface engineering of NP chemistry that hitherto was impossible using existing approaches.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Sussman
authors.forename: Michael B
authors.initials: MB
authors.lastname: Clarke
authors.forename: V Prasad
authors.initials: VP
authors.lastname: Shastri
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007526:Isoelectric Point; D019344:Lactic Acid / Q000138:chemical synthesis*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D011100:Polyglycolic Acid / Q000138:chemical synthesis*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis*; D011134:Polysaccharides / Q000737:chemistry; D012995:Solubility; D013059:Spectrum Analysis, Raman; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D011134:Polysaccharides; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols