Nanospheres formulated from L-tyrosine polyphosphate as a potential intracellular delivery device.
Current delivery devices for drugs and genes such as films and microspheres are usually formulated from polymers that degrade over a period of months. In general, these delivery systems are designed to achieve an extracellular release of their encapsulated drugs. For drugs that require interaction with cellular machinery, the efficacies of both macroscopic and microscopic delivery systems are normally low. In contrast, nano-sized drug delivery vehicles could achieve high delivery efficiencies, but they must degrade quickly, and the delivery system itself should be nontoxic to cells. In this aspect, biodegradable nanospheres formulated from l-tyrosine polyphosphate (LTP) have been produced from an emulsion of oil and water for the potential use as an intracellular delivery device. Scanning electron microscopy (SEM) and dynamic laser light scattering (DLS) show that LTP nanospheres possess a diameter range between 100 and 600 nm. SEM reveals nanospheres formulated from LTP are spherical and smooth. Additionally, DLS studies demonstrate that nanospheres degrade hydrolytically in 7 days. Confocal microscopy reveals LTP nanospheres are internalized within human fibroblasts. Finally, the cell viability after exposure to LTP nanospheres and determined with a LIVE/DEAD Cell Viability Assay is comparable to a buffer control. In conclusion, our nanospheres have been shown to be nontoxic to human cells, possess the appropriate size for endocytosis by human cells, and degrade within 7 days. Therefore LTP nanospheres can be used for a sustained intracellular delivery device.
Ditto
Andrew J
AJ
Department of Biomedical Engineering, The University of Akron, Sidney Olson Research Center, Akron, OH 44325, USA.
Shah
Parth N
PN
Lopina
Stephanie T
ST
Yun
Yang H
YH
D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D004655:Emulsions; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007834:Lasers; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D054118:Nanospheres; D010755:Organophosphates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000633:toxicity; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000633:toxicity; D013499:Surface Properties; D014443:Tyrosine / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity
D004337:Drug Carriers; D004655:Emulsions; D010755:Organophosphates; D011108:Polymers; C542009:tyrosine polyphosphate; D014443:Tyrosine