Functionalized Polymeric Nanoparticles
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Functionalized Polymeric Nanoparticles Eric Sussman1, Michael Clark, Jr.2, and V. Prasad Shastri3,4 ([email protected]) 1 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104. 2 Rohm and Haas Company, 727 Norristown Road, Spring House, PA 19477. 3 Department of Materials Science and Engineering, University of Pennsylvania, 3231 Walnut Street, Philadelphia, Pennsylvania 19104 4 Joseph Stokes Research Institute, Children’s Hospital of Philadelphia, 3516 Civic Center Boulevard, Philadelphia, Pennsylvania 19104
ABSTRACT Surface-functionalized polymeric nanoparticles (NP) are a versatile medium for drug delivery and imaging. The surface functionality is typically exploited to introduce molecules such as polymers and biomolecules to improve cellular localization, DNA binding and circulation. NP bearing surface functionality are typically prepared from polymers possessing functionalizable backbones or by layer-by-layer assembly of polyelectrolytes onto unmodified particles. We have developed a process to produce functionalized polymeric NP in a single step using non-functionalized polymers. This is achieved by the entrapment of polymeric functional moieties from an aqueous phase in a rapidly solidifying polymer core. NP were characterized using light scattering, scanning electron microscopy, zeta potential (ζ) measurement, fluorescent microscopy, and X-ray photoelectron spectroscopy (XPS). Stable NP ranging in diameter from 70 to 400nm with narrow polydispersity (PDI) can be produced by this process. The presence of functional moieties on the NP surface was verified by isoelectric point measurement and XPS. We foresee a number of uses for these functionalized nanoparticles, including drug delivery and modification of hard and soft material surfaces (both synthetic and biological) for tissue engineering.
INTRODUCTION Polymeric nanoparticles are being increasing investigated for drug delivery applications [1,2]. Their efficacy is largely determined by their ability to avoid clearance by the RES and localize in regions of maximum therapeutic value, both of which are determined by the surface chemistry of the NP [3]. Functionalized NP are typically produced by a phase inversion (coacervation) process [4-6] using polymers possessing the desired functionality as a part of the polymer backbone. We have developed a novel process for producing surface-functionalized polymeric NP from polymers such as poly(lactic-co-glycolide) and poly(L-lactic acid), whose backbone bear non functional groups. This was achieved by tailoring the solvation core of the polymer such that the addition of an aqueous phase leads to spontaneous formation of NP and the surface entrapment of any polyelectrolyte or water-soluble polymer in the aqueous phase.
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MATERIALS Poly(dl-lactide-co-glycolide) (PLGA, RG 503,MW=30,000) and poly(L-lactide) (PLA) MW = 70,000, inherent viscosity 1.20 dL/g in CHCl3) were purchased from Birmingham Polymers (Birmingham, AL, USA) and were purified by precipitation from
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