Delivering DNA from photocrosslinked, surface eroding polyanhydrides.
Sustained delivery of DNA has the potential to enhance long-term gene therapy; however, precise control of a wide range of DNA release profiles may be needed. In this work, multifunctional anhydride monomers were photocrosslinked to produce hydrophobic, highly crosslinked polymer networks that degrade by surface erosion. Surface-eroding polymers can deliver molecules of a wide range of sizes at sustained, steady rates, which is advantageous for DNA delivery, where the high molecular weight may complicate control of the release profiles. When plasmid DNA was released from photocrosslinked polyanhydride matrices, DNA recovery was low (approximately 25%). Electrophoresis indicated that the plasmid DNA was released primarily in the relaxed and supercoiled forms, yet the relative fraction of released DNA in the supercoiled form decreased over time. To improve DNA recovery and reduce the damaging effects of polymer degradation, DNA was pre-encapsulated in alginate microparticles, which served as a temporary coating that quickly dissolved upon microparticle release from the polyanhydride matrix. As photocrosslinked polyanhydrides have highly predictable drug release profiles that depend on the polymer erosion rate and implant geometry and not on the entrapped molecule size, they can serve dual purposes in many biomaterial applications where structural support and drug release would be beneficial.
Quick
Deborah J
DJ
Department of Chemical and Biological Engineering, University of Colorado, ECCH 111, UCB 424, Boulder, CO 80309, USA.
Macdonald
Kelly K
KK
Anseth
Kristi S
KS
D000464:Alginates; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000528:radiation effects; D016503:Drug Delivery Systems; D004355:Drug Stability; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D009690:Nucleic Acid Conformation; D010777:Photochemistry; D010957:Plasmids; D049388:Polyanhydrides / Q000737:chemistry* / Q000528:radiation effects; D013997:Time Factors
D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D049388:Polyanhydrides; D020723:Glucuronic Acid; D004247:DNA