TAT Peptide-Conjugated Magnetic PLA-PEG Nanocapsules for the Targeted Delivery of Paclitaxel: In Vitro and Cell Studies.
Paclitaxel (PTX) and organophilic iron oxide nanocrystals of 7 nm average size were co-encapsulated in the oily core of poly(lactide)-poly(ethyleneglycol) (PLA-PEG) nanocapsules in order to develop magnetically responsive nanocarriers of PTX. The nanocapsules were prepared by a solvent displacement technique and exhibited satisfactory drug and iron oxide loading efficiency, high colloidal stability, and sustained drug release properties. Drug release also proved responsive to an alternating magnetic field. Magnetophoresis experiments showed that the magnetic responsiveness of the nanocapsules depended on their SPION content. The PTX-loaded nanocapsules exhibited comparable to free PTX cytotoxicity against the A549 lung cancer cell line at 24 h of incubation but higher cytotoxicity than free drug at 48 h of incubation. The conjugation of a cysteine-modified TAT peptide (HCys-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH2) on the surface of the nanocapsules resulted to highly increased uptake of nanocapsules by cancer cells, as well as to profound improvement of their cytotoxicity against the cancer cells. The results obtained justify further investigation of the prospects of these multifunctional PLA-PEG nanocapsules as a targeted delivery system of paclitaxel.
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece.
Kelly
K
Koutsiouki
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece.
Athina
A
Angelopoulou
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece.
Eirini
E
Ioannou
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece.
Efstathia
E
Voulgari
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece.|Department of Materials Science, University of Patras, 26500, Patras, Greece.
Andreas
A
Sergides
Department of Chemistry, University of Patras, 26500, Patras, Greece.
George E
GE
Magoulas
Department of Materials Science, University of Patras, 26500, Patras, Greece.
Aristides
A
Bakandritsos
Department of Pharmacy, University of Patras, Rio, 26500, Patras, Greece. avgoust@upatras.gr.
Konstantinos
K
Avgoustakis
D000072283:A549 Cells; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D065546:Drug Liberation / Q000187:drug effects; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D003692:Delayed-Action Preparations; D053769:Nanocapsules; D010446:Peptide Fragments; D011091:Polyesters; D011092:Polyethylene Glycols; C083464:poly(ethyleneglycol-lactide); D017239:Paclitaxel
PLA-PEG; TAT peptide; drug delivery; iron oxide nanocrystals; nanocapsules; paclitaxel