Lysine-based peptide-functionalized PLGA foams for controlled DNA delivery

• Published in: Journal of controlled release 2009-08, Vol.138 (1), p.64-70
• Main Authors: Nie, Hemin, Khew, Shih Tak, Lee, Lai Yeng, Poh, Kai Ling, Tong, Yen Wah, Wang, Chi-Hwa
• Format: Article
• Language: English
• Subjects: Adsorption; Animals; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Cell Survival - drug effects; Cells, Cultured; Delayed-Action Preparations - chemistry; DNA - administration & dosage; DNA - chemistry; DNA - genetics; DNA delivery; Gene Expression; General pharmacology; Lactic Acid - chemistry; Lactic Acid - toxicity; Lysine - chemistry; Lysine peptide; Medical sciences; Peptides - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids - administration & dosage; Plasmids - genetics; Poly( d, l-lactic- co-glycolic acid); Polyglycolic Acid - chemistry; Polyglycolic Acid - toxicity; Porosity; Rats; Spectrometry, X-Ray Emission; Static Electricity; Supercritical CO 2 foaming; Surface Properties; Transfection
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2009.04.027

Due to its hydrophobicity and negatively charged surfaces, PLGA-based scaffolds have encountered problems in controlled-release and tissue engineering applications. The effects of charge modification of PLGA micro-porous foams on DNA delivery and DNA transfection are investigated herein. Tailor-designed l-lysine peptides (K4 and K20) were employed to modify the surface charge of PLGA foams using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide cross linkers and the effects of charge modification of PLGA were examined in three main aspects: DNA adsorption, DNA release properties and DNA transfection. Successful conjugation of peptide and DNA adsorption were verified by X-ray photoelectron spectroscopy. A plasmid encoding bone morphogenetic protein-2 (BMP2) was used throughout the current study and the results indicate that adsorption capacity and release behavior of DNA were highly dependent on the charge properties of the foam surfaces. The release rates of DNA from the K4- and K20-functionalized foams are more sustainable as compared to the blank foam. As a result, the sustained release of DNA from modified foams led to negligible cytotoxicity and sustained expression of DNA which is favorable for DNA delivery and tissue engineering application. Furthermore, the ease of fabrication and modification of PLGA foams makes it a promising DNA delivery device. Curves of DNA cumulative release from blank foam (F0), K4 modified foam (F1) and K20 modified foam (F2) (mean ± S.D., n = 3). [Display omitted]