Targeted binding of PLA microparticles with lipid-PEG-tethered ligands.
Solid core polymeric particles are an attractive delivery vehicle as they can efficiently encapsulate drugs of different physical and chemical characteristics. However, the effective targeting of such particles for therapeutic purposes has been somewhat elusive. Here, we report novel polymeric particles comprised of poly(lactic acid) (PLA) with incorporated poly(ethylene glycol)-lipids (PEG-lipids). Particles are characterized for morphology, surface charge, and composition with field-emission scanning electron microscopy (FESEM), zeta potential measurements, and proton nuclear magnetic resonance ((1)H NMR) spectroscopy, respectively. The surface densities of PEG lipids determined by (1)H NMR and particle size distributions are consistent with scaling theory for adsorption of chains onto a surface. We observe significant binding of liganded PEG-lipid tethers when the molecular weight is greater than the unliganded PEG-lipids for significant binding events. Importantly, the binding is not completely lost when the unliganded PEG molecular weight is greater than the liganded PEG-lipid tether. We observe a similar trend for the lower affinity ligand (thioctic acid), but the degree of binding is significantly lower than the high affinity ligand (biotin). This novel technique used to fabricate these liganded particles combined with the lipid bilayer binding studies provides a platform for systematic optimization of particle binding.
Duncanson
Wynter J
WJ
Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Figa
Michael A
MA
Hallock
Kevin
K
Zalipsky
Samuel
S
Hamilton
James A
JA
Wong
Joyce Y
JY
D001672:Biocompatible Materials / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry*; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000737:chemistry*; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008863:Microspheres; D009821:Oils; D010316:Particle Size; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D013499:Surface Properties; D008063:Thioctic Acid / Q000737:chemistry; D014867:Water / Q000737:chemistry
D001672:Biocompatible Materials; D008024:Ligands; D008055:Lipids; D009821:Oils; D011091:Polyesters; D011108:Polymers; D014867:Water; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D001710:Biotin; D008063:Thioctic Acid
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