title: Combinatorial co-encapsulation of hydrophobic molecules in poly(lactide-co-glycolide) microparticles.
abstract: There is great interest for developing poly(lactide-co-glycolide) (PLGA) based particles for targeted delivery and controlled release of encapsulated biological molecules. These PLGA particles can be used to deliver proteins, small molecule drugs and nucleotides. Furthermore, it has been shown that the co-encapsulation of multiple factors in PLGA particles can generate synergistic responses, and can also provide theranostic capability. However, the number of possible unique particle formulations that may be generated by the combination of different components in a particle increases dramatically with each new component, and currently, there is no method to generate large libraries of unique PLGA particles. In order to address this gap, we have developed a high-throughput methodology to produce hundreds of small batches of particles. The particles are generated in multi-well plate wells by a modified oil-in-water emulsion technique. In order to demonstrate the versatility of this technique, combinatorial formulations of six different loading concentrations of three fluorescent dyes were fabricated giving rise to 216 unique PLGA particle formulations. We demonstrate systematic and well-controlled combinatorial loading of hydrophobic molecules into the particles. This parallel particle production (PPP) methodology potentiates the generation of hundreds of different combinatorial particle formulations with multiple co-encapsulates in less than 24 h in standard polystyrene multi-well plates, thus providing rapid, low cost, high-throughput production. We envision that such a PPP library of particles encapsulating combinations of drugs and imaging modalities can subsequently be tested on small populations of cells in a high-throughput fashion, and represents a step toward personalized medicine.
authors: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611-6131, USA.
authors: Abhinav P
authors: AP
authors: Acharya
authors: Jamal S
authors: JS
authors: Lewis
authors: Benjamin G
authors: BG
authors: Keselowsky
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism; D004339:Drug Compounding; D005456:Fluorescent Dyes / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D005456:Fluorescent Dyes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
references: J Drug Deliv. 2012;2012:767839
references: 22506124
references: J Pharm Sci. 2008 Jul;97(7):2448-61
references: 17918737
references: J Comb Chem. 2010 Jan-Feb;12(1):51-6
references: 19902908
references: Pharm Res. 2004 Dec;21(12):2384-91
references: 15648273
references: J Vis Exp. 2012 Sep 06;(67):
references: 22987047
references: Acta Biomater. 2010 Sep;6(9):3491-8
references: 20226885
references: Biomaterials. 2008 Dec;29(36):4736-50
references: 18829103
references: Nat Biotechnol. 2004 Jul;22(7):863-6
references: 15195101
references: Int J Pharm. 2002 Aug 21;242(1-2):277-80
references: 12176263
references: Nat Mater. 2009 Feb;8(2):151-8
references: 19136947
references: Hum Vaccin. 2011 Jan 1;7(1):37-44
references: 21157186
references: Biomaterials. 2000 Dec;21(23):2475-90
references: 11055295
references: Mol Ther. 2008 Dec;16(12):2011-21
references: 18813280
references: Acta Biomater. 2010 Jul;6(7):2621-30
references: 20097314
references: J Control Release. 2010 Sep 15;146(3):341-8
references: 20595029
references: Biomaterials. 2010 Mar;31(7):1604-11
references: 19932505
references: Biomaterials. 2010 Oct;31(29):7444-54
references: 20637504
references: Expert Rev Mol Diagn. 2009 May;9(4):325-41
references: 19435455
references: Adv Drug Deliv Rev. 2011 Sep 10;63(10-11):943-55
references: 21679733
references: J Microencapsul. 1998 Jan-Feb;15(1):107-19
references: 9463812
references: J Control Release. 2002 Dec 13;85(1-3):247-62
references: 12480329
references: Acta Biomater. 2011 Jan;7(1):180-92
references: 20807596
references: Biomaterials. 2009 Sep;30(25):4168-77
references: 19477505
references: Biomaterials. 2012 Oct;33(29):7221-32
references: 22796161
references: Dev Biol Stand. 1998;92:63-78
references: 9554260