Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA–PEG block copolymers

• Published in: Journal of controlled release Vol. 89; no. 2; pp. 341 - 353
• Main Authors: Luu, Y.K., Kim, K., Hsiao, B.S., Chu, B., Hadjiargyrou, M.
• Format: Journal Article
• Language: English
• Published: Legacy CDMS Elsevier B.V 29.04.2003; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Line; DNA - administration & dosage; DNA - genetics; Drug Delivery Systems - methods; Electrospinning; Gene delivery; General pharmacology; Lactates - administration & dosage; Lactic Acid - administration & dosage; Life Sciences (General); Medical sciences; Mice; Nanotechnology - methods; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLA–PEG block copolymer; PLGA; Polyethylene Glycols - administration & dosage; Polyglycolic Acid - administration & dosage; Polymers - administration & dosage; Space life sciences; Tissue engineering; Transfection - methods; Electrospinning; Gene delivery; PLGA; PLA–PEG block copolymer; Tissue engineering; Non-Nasa Center; Nasa Discipline Cell Biology; Nasa Program Fundamental Space Biology; Glycolic acid copolymer; Delivery system; Pharmaceutical technology; Control release polymer; Gene delivery: Tissue engineering; Drug carrier; Anhydride polymer; In vitro; Ethylene oxide polymer; Plasmid; Anhydride copolymer; Ester copolymer; Lactic acid polymer; Transfection; DNA; Dosage form; Active ingredient; Electrospinning: PLGA: PLA-PEG block copolymer; Block copolymer; Release; NASA Program Fundamental Space Biology; NASA Discipline Cell Biology; Non-NASA Center
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(03)00097-X

The present work utilizes electrospinning to fabricate synthetic polymer/DNA composite scaffolds for therapeutic application in gene delivery for tissue engineering. The scaffolds are non-woven, nano-fibered, membranous structures composed predominantly of poly(lactide-co-glycolide) (PLGA) random copolymer and a poly( d, l-lactide)–poly(ethylene glycol) (PLA–PEG) block copolymer. Release of plasmid DNA from the scaffolds was sustained over a 20-day study period, with maximum release occurring at ∼2 h. Cumulative release profiles indicated amounts released were approximately 68–80% of the initially loaded DNA. Variations in the PLGA to PLA–PEG block copolymer ratio vastly affected the overall structural morphology, as well as both the rate and efficiency of DNA release. Results indicated that DNA released directly from these electrospun scaffolds was indeed intact, capable of cellular transfection, and successfully encoded the protein β-galactosidase. When tested under tensile loads, the electrospun polymer/DNA composite scaffolds exhibited tensile moduli of ∼35 MPa, with ∼45% strain initially. These values approximate those of skin and cartilage. Taken together, this work represents the first successful demonstration of plasmid DNA incorporation into a polymer scaffold using electrospinning.