Injectable self-assembled block copolymers for sustained gene and drug co-delivery: an in vitro study.
A temperature-responsive pentablock copolymer (PB) was designed to deliver DNA and provide prolonged gene expression by forming a thermogelling release depot after subcutaneous or intratumoral injection. A synthetic barrier gel was developed based on poly(ethylene glycol) diacrylate to enable the released vectors to instantly and continuously transfect cultured cells. The aim of this setup was to provide a simple and controlled in vitro system to mimic tumor matrix to optimize the release system and to study the influence of the continuous and sustained release of the polyplexes on the in vitro transfection. The porosity of the barrier gel was adjusted by addition and removal of Pluronic F127 (PL), and the properties of the gel were characterized by visual inspection and scanning electron microscopy (SEM). Concentrated PB-based vector was administered to the barrier gel and allowed to be released to the buffer. We found that most of feed vector could be released from the barrier gel without unpacking the polymer-DNA complexes. Based on the specific construction of the PB-based vectors, an anti-cancer drug paclitaxel (PTX) was further loaded into the same vector designed for DNA delivery, thus formulating a gene and drug co-delivery system. This system was tested for sustained delivery to human ovarian carcinoma cells SKOV3 using the barrier gel in vitro as a tumor mimic. Transfection efficiency was found to be significantly enhanced by co-delivering PTX, while PTX also showed its effect as an anti-cancer drug to induce cell death. Yet both of the two effects of PTX shown in SKOV3 cells turned out to be dramatically weaker in ARPE-19 cells, a human non-cancerous cell line, which might be related to the nature of the vector itself. Instant release of vectors showed the ability to maintain transfection up to the fourth day, making the gene expression stable at least for the first 5 days. Further study is still needed to improve the duration of effective release.
Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011-2230, United States.
Bingqi
B
Zhang
Feng
F
Jia
Michael Q
MQ
Fleming
Surya K
SK
Mallapragada
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D017930:Genes, Reporter; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D008156:Luciferases / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009369:Neoplasms / Q000628:therapy; D017239:Paclitaxel / Q000008:administration & dosage*; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; C437167:poly(ethylene glycol)diacrylate; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases; D017239:Paclitaxel