title: Encapsulation of paclitaxel in macromolecular nanoshells.
abstract: An electrostatic layer-by-layer self-assembly technique was used to encapsulate solid core paclitaxel nanoparticles within a polymeric nanometer-scale shell. This approach provides a new strategy for the development of polymeric vehicles that control drug release and target diseased tissues and cells specific to the ailment, such as breast cancer. Core paclitaxel nanoparticles, 153 +/- 28 nm in diameter, were prepared using a modified nanoprecipitation technique. A nanoshell composed of multilayered polyelectrolytes, poly(allylamine hydrochloride) and poly(styrene-4-sulfonate) was assembled stepwise onto core charged drug nanoparticles. In vitro studies were performed to determine the anticancer activity of paclitaxel core-shell nanoparticles. Paclitaxel core-shell nanoparticles induced cell cycle arrest in the G2/M phase after 24 and 48 h of incubation with a human breast carcinoma cell line, MCF-7. Changes in MCF-7 cell morphology, fragmentation of the nucleus, and loss of cell-cell contacts indicated that the cells responded to paclitaxel core nanoparticles upon treatment for 24 and 48 h. Cells arrested in G2/M phase illustrated abnormal microtubule and actin cytoskeleton morphology. The core-shell drug nanoparticles fabricated using this procedure provide a new approach in the delivery of paclitaxel devoid of Cremophor EL, a solvent that causes adverse side effects in patients undergoing chemotherapy for treatment of metastasized mammary cancers.
authors.affiliation: Departments of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Alisar S
authors.initials: AS
authors.lastname: Zahr
authors.forename: Michael V
authors.initials: MV
authors.lastname: Pishko
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D016503:Drug Delivery Systems; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D011108:Polymers; D012997:Solvents; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol