TY - JOUR
T1 - Targeted binding of PLA microparticles with lipid-PEG-tethered ligands
AU - Duncanson, Wynter J.
AU - Figa, Michael A.
AU - Hallock, Kevin
AU - Zalipsky, Samuel
AU - Hamilton, James A.
AU - Wong, Joyce Y.
N1 - Funding Information:
We acknowledge financial support from ALZA Corporation and the National Institutes of Health (NIH HL72900S) to JYW, and the NIH P50 HL083801 (JAH, JYW). The authors thank Nasreen Mullah (ALZA) for her technical assistance in synthesis of lipopolymer conjugates. We also thank C. Marques (CNRS) and E. Amstad for helpful and insightful discussions.
PY - 2007/11
Y1 - 2007/11
N2 - 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 (1H NMR) spectroscopy, respectively. The surface densities of PEG lipids determined by 1H 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.
AB - 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 (1H NMR) spectroscopy, respectively. The surface densities of PEG lipids determined by 1H 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.
KW - Drug delivery
KW - Lipid
KW - Microsphere
KW - Poly(lactic acid)
KW - Surface modification
UR - http://www.scopus.com/inward/record.url?scp=34548461265&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548461265&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2007.05.044
DO - 10.1016/j.biomaterials.2007.05.044
M3 - Article
C2 - 17707503
AN - SCOPUS:34548461265
VL - 28
SP - 4991
EP - 4999
JO - Biomaterials
JF - Biomaterials
SN - 0142-9612
IS - 33
ER -