title: Targeted binding of PLA microparticles with lipid-PEG-tethered ligands.
abstract: 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.
authors: Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
authors: Wynter J
authors: WJ
authors: Duncanson
authors: Michael A
authors: MA
authors: Figa
authors: Kevin
authors: K
authors: Hallock
authors: Samuel
authors: S
authors: Zalipsky
authors: James A
authors: JA
authors: Hamilton
authors: Joyce Y
authors: JY
authors: Wong
mesh_terms: 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
chemical_list: 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
references: Adv Drug Deliv Rev. 2005 Dec 13;57(14):2047-52
references: 16298454
references: Biomaterials. 1997 Jan;18(1):27-30
references: 9003893
references: Pharm Res. 1998 Sep;15(9):1340-7
references: 9755883
references: Biomaterials. 2005 Oct;26(28):5727-36
references: 15878378
references: Biomaterials. 2005 Jan;26(2):117-24
references: 15207458
references: Langmuir. 2005 Jun 7;21(12):5605-15
references: 15924497
references: Int J Pharm. 2004 Jul 8;278(2):293-301
references: 15196634
references: Lasers Surg Med. 2003;33(2):119-25
references: 12913884
references: FEBS Lett. 1984 Feb 13;167(1):79-82
references: 6698206
references: Langmuir. 2005 Nov 22;21(24):11342-51
references: 16285809
references: FEBS Lett. 1994 Oct 10;353(1):71-4
references: 7926026
references: Science. 1997 Feb 7;275(5301):820-2
references: 9012346
references: Biomaterials. 2003 Dec;24(27):5037-44
references: 14559017
references: Biotechnol Annu Rev. 2006;12:301-47
references: 17045198
references: Biomaterials. 2003 Nov;24(24):4529-37
references: 12922162
references: Science. 2004 Mar 19;303(5665):1818-22
references: 15031496
references: J Biomed Mater Res A. 2003 Aug 1;66(2):347-55
references: 12889005
references: Colloids Surf B Biointerfaces. 2000 Oct 1;18(3-4):301-313
references: 10915952
references: Adv Drug Deliv Rev. 2004 Apr 29;56(8):1177-92
references: 15094214
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15895-900
references: 14668435
references: Pharm Res. 1997 May;14(5):657-61
references: 9165539
references: Biomaterials. 2005 Feb;26(6):661-70
references: 15282144
references: Pharm Res. 1998 Feb;15(2):270-5
references: 9523314
references: Biomaterials. 2004 Jun;25(14):2843-9
references: 14962562
references: J Pharm Sci. 1995 Apr;84(4):493-8
references: 7629743
references: Eur J Pharm Biopharm. 2004 Nov;58(3):483-90
references: 15451522
references: J Control Release. 2004 Aug 11;98(2):231-44
references: 15262415
references: Eur J Immunol. 2006 Feb;36(2):446-56
references: 16421944
references: Anal Chem. 2005 Sep 1;77(17):5453-9
references: 16131052
references: Adv Drug Deliv Rev. 1998 Dec 1;34(2-3):261-283
references: 10837681
references: J Control Release. 2002 Jul 18;82(1):105-14
references: 12106981
references: Biophys J. 1994 May;66(5):1479-88
references: 8061197
references: J Biomater Sci Polym Ed. 2004;15(9):1137-51
references: 15503631
references: Eur J Med Chem. 2007 Jan;42(1):114-24
references: 17011671
references: Pharm Acta Helv. 1996 Jul;71(2):121-8
references: 8810578
references: Methods Enzymol. 2004;387:50-69
references: 15172157
references: Science. 2001 Jul 20;293(5529):465-8
references: 11463908
references: Adv Drug Deliv Rev. 1995 Sep;16(2-3):215-233
references: 25170183
references: Langmuir. 2004 Nov 9;20(23):10252-9
references: 15518521
references: J Control Release. 1998 Dec 4;56(1-3):197-208
references: 9801443
references: Bioconjug Chem. 1999 Mar-Apr;10(2):289-98
references: 10077479
references: Biochem Biophys Res Commun. 2006 Nov 24;350(3):508-13
references: 17027652