Poly(lactide-co-glycolide) nanoparticle assembly for highly efficient delivery of potent therapeutic agents from medical devices.
Controlled delivery of therapeutic agents from medical devices can improve their safety and effectiveness in vivo, by ameliorating the surrounding tissue responses and thus maintaining the functional integrity of the devices. Previously, we presented a new method for providing simultaneous controlled delivery from medical devices, by surface assembly of biodegradable polymer nanoparticles (NPs) encapsulating fluorescent dyes. Here, we continue our investigation with NPs loaded with therapeutic agents, dexamethasone (DEX) or plasmid DNA, and evaluated the bioactivity of the released molecules with macrophage cells associated with inflammation. Over a period of one week, NPs encapsulating DEX released 24.9+/-0.8ng from the probe surface and was successful at suppressing macrophage cell growth by 40+/-10%. This percentage of suppression corresponded to approximately 100% drug delivery efficiency, in comparison with the unencapsulated drug. DNA NP coatings, in contrast, released approximately 1ng of plasmid DNA and were effective at transfecting macrophage cells to express the luciferase gene at 300+/-200 relative luminescence/mg total protein. This amount of luciferase activity corresponded to 100% gene delivery efficiency. Thus, NP coatings were capable of providing continuous release of bioactive agents in sufficient quantities to induce relevant biological effects in cell culture studies. These coatings also remained intact, even after 14 days of incubation with phosphate buffered saline. Although the maximum loading for NP coatings is inherently lower than the more established matrix coating, our study suggests that the NP coatings are a more versatile and efficient approach toward drug delivery or gene delivery from a medical device surface and are perhaps best suited for continuous release of highly potent therapeutic agents.
Department of Biomedical Engineering, Yale University, Malone Engineering Center, Room 414, 55 Prospect Street, New Haven, CT 06511, USA.
Catherine T
CT
Lo
Paul R
PR
Van Tassel
W Mark
WM
Saltzman
D004247:DNA / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004864:Equipment and Supplies; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D053758:Nanoparticles; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry*
D005456:Fluorescent Dyes; D011098:Polyglactin 910; D003907:Dexamethasone; D004247:DNA