Poly(ester-anhydride):poly(beta-amino ester) micro- and nanospheres: DNA encapsulation and cellular transfection.
Poly(ester-anhydride) delivery devices allow flexibility regarding carrier dimensions (micro- versus nanospheres), degradation rate (anhydride versus ester hydrolysis), and surface labeling (through the anhydride functional unit), and were therefore tested for DNA encapsulation and transfection of a macrophage P388D1 cell line. Poly(l-lactic acid-co-sebacic anhydride) and poly(l-lactic acid-co-adipic anhydride) were synthesized through melt condensation, mixed with 25 wt.% poly(beta-amino ester), and formulated with plasmid DNA (encoding firefly luciferase) into micro- and nanospheres using a double emulsion/solvent evaporation technique. The micro- and nanospheres were then characterized (size, morphology, zeta potential, DNA release) and assayed for DNA encapsulation and cellular transfection over a range of poly(ester-anhydride) copolymer ratios. Poly(ester-anhydride):poly(beta-amino ester) composite microspheres (6-12 microm) and nanospheres (449-1031 nm), generated with copolymers containing between 0 and 25% total polyanhydride content, encapsulated plasmid DNA (>or=20% encapsulation efficiency). Within this polyanhydride range, poly(adipic anhydride) copolymers provided DNA encapsulation at an increased anhydride content (10%, microspheres; 10-25%, nanospheres) compared to poly(sebacic anhydride) copolymers (1%, microspheres and nanospheres) with cellular transfection correlating with the observed DNA encapsulation.
Pfeifer
Blaine A
BA
Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155, USA. blaine.pfeifer@tufts.edu
Burdick
Jason A
JA
Little
Steve R
SR
Langer
Robert
R
D000272:Adipates / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism*; D003652:Decanoic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008863:Microspheres; D043942:Nanotubes; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection
D000272:Adipates; D003652:Decanoic Acids; D011091:Polyesters; D011108:Polymers; C507263:poly(L-lactic acid-co-adipic anhydride); C507262:poly(L-lactic acid-co-sebacic anhydride); D019344:Lactic Acid; D004247:DNA