Paclitaxel-conjugated PEG and arginine-grafted bioreducible poly (disulfide amine) micelles for co-delivery of drug and gene

Abstract We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG3.5k -Paclitaxel (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and drug. The APP polymer self-assembled into cationic polymeri...

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Bibliographic Details
Published in:Biomaterials 2012-11, Vol.33 (32), p.8122-8130
Main Authors: Nam, Kihoon, Nam, Hye Yeong, Kim, Pyung-Hwan, Kim, Sung Wan
Format: Article
Language:English
Subjects:
absorption
Advanced Basic Science
Animals
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
Arginine - chemistry
Bioreducible polymer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cationic
Cell Line, Tumor
Cellular
Dentistry
DNA - administration & dosage
DNA - genetics
Drug delivery
Drug delivery systems
Drugs
ethylene glycol
Female
Gene therapy
Genes
Glutathione - antagonists & inhibitors
Glutathione - metabolism
Humans
Interleukin-12
Interleukin-12 - genetics
luciferase
Mice
Micelles
Monitors
Paclitaxel
Paclitaxel - administration & dosage
Paclitaxel - chemistry
Paclitaxel - pharmacology
Particle Size
plasmids
Polyamines - chemistry
Polyethylene Glycols - chemistry
Polymeric micelle
polymers
Surgical implants
Transfection
zeta potential
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Summary:Abstract We developed a paclitaxel-conjugated polymeric micelle, ABP-PEG3.5k -Paclitaxel (APP) consisting of poly (ethylene glycol) (PEG) and arginine-grafted poly (cystaminebisacrylamide-diaminohexane) (ABP) for the co-delivery of gene and drug. The APP polymer self-assembled into cationic polymeric micelles with a critical micelle concentration (CMC) value of approximately 0.062 mg/mL, which was determined from measurements of the UV absorption of pyrene. The micelles have an average size of about 3 nm and a zeta potential of about +14 mV. Due to the positive surface charge, APP micelles formed polyplexes with plasmid DNA approximately 200 nm in diameter. The luciferase gene and mouse interleukin-12 (IL-12) gene was used to monitor gene delivery potency. APP polyplexes showed increased gene delivery efficiency and cellular uptake with higher anticancer potency than paclitaxel alone. These results demonstrate that an APP micelle-based delivery system is well suitable for the co-delivery of gene and drug.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.07.031