A comparison between polymeric microsphere and bacterial vectors for macrophage P388D1 gene delivery

作者：Parsa Saba; Wang Yong; Fuller Jason; Langer Robert; Pfeifer Blaine A^*

来源：Pharmaceutical Research, 2008, 25(5): 1202-1208.

DOI：10.1007/s11095-008-9563-x

• bacterial vectors
• E. coli
• gene delivery
• high throughput
• polymeric microspheres

Purpose: The purpose of this study was to compare bacterial and polymeric gene delivery devices for the ability to deliver plasmid DNA to a murine macrophage P388D1 cell line.
Methods: An 85:15 ratio of poly(lactic-co-glycolic acid) (PLGA) and poly(beta-amino ester) polymers were formulated into microspheres that physically entrapped plasmid DNA encoding for the firefly luciferase reporter gene; whereas, the same plasmid was biologically transformed into a strain of Escherichia coli engineered to produce recombinant listeriolysin O. The two delivery devices were then tested for gene delivery and dosage effects using a macrophage cell line with both assays taking advantage of a 96-well high throughput format to quantify and compare each vector type.
Results: Gene delivery was comparable for both vectors at higher vector dosages while lower dosages showed an improved delivery for the microsphere vectors. Delivery efficiency (defined as luciferase measurement/mg cellular protein/ng DNA delivered) was 881 luminescence mg(-1) ng(-1) for polymeric microspheres compared to 171 luminescence mg(-1) ng(-1) for the bacterial vectors.
Conclusions: A first head-to-head comparison between polymeric and bacterial gene delivery vectors shows a delivery advantage for polymeric microspheres that must also be evaluated in light of vector production, storage, and future potential.

• 出版日期2008-5