This study investigated the potential of creating a charged polymeric micelle-based nucleic acid delivery system that could easily be reconstituted by the addition of water. (PLGA 36kDa ) 2 -bbPEI 25kDa (PLGA MW 36kDa, bPEI M w 25kDa, PLGA:bPEI block ratio = 2) was synthesized and used to prepare cationic micelles. The copolymer retained proton-buffering capability from the bPEI block within the endosomal pH range. Micelle/pDNA complexes retained their particle size (100-150 nm) and surface charge (30-40 mV) following reconstitution. It was found that adding a small amount of low molecular weight bPEI (1.8 kDa) completely shielded pDNA in the micelle/pDNA complexes and enhanced transfection efficiency 50-100 fold for both fresh and reconstituted complexes without affecting complex size. Transfection efficiency for "reconstituted" micelle/pDNA/bPEI 1.8kDa (WR 1) complexes was 16-fold higher than its "fresh" counterpart. Although transfection levels achieved using "reconstituted" micelle/pDNA/ bPEI 1.8kDa complexes were 3.6-fold lower than control "fresh" bPEI 25kDa /pDNA (N/P 5) complexes, transfection levels were 39-fold higher than "reconstituted" bPEI 25kDa /pDNA (N/P 5) complexes. The micelle/pDNA/bPEI 1.8kDa system showed very low cytotoxicity in MCF7 cells even with pDNA doses up to 20 μg, and transfection levels increased linearly with increasing pDNA dose. These results indicate that this PLGA-b-bPEI polymeric micelle-based system is well suited as a reconstitutable gene delivery system, and has high potential for use as a delivery system for gene therapy applications.

Nanoparticle-based drug delivery systems are appealing because, among other properties, they are easily manufactured and have the capacity to encapsulate a wide variety of drugs, many of which are not directly miscible with water. This review classifies nanoparticles into three broad categories based upon material composition: bio-inspired systems, synthetic systems, and inorganic systems. Each has distinct properties suitable for drug delivery applications, including their structure, composition, and pharmacokinetics (including clearance and uptake mechanisms), making each uniquely suitable for certain types of drugs. Furthermore, nanoparticles can be customized, making them ideal for a variety of applications. Advantages and disadvantages of the different systems are discussed. Strategies for improving nanoparticle efficacy include adding targeting agents on the nanoparticle surface, altering the degradation profile to control drug release, or PEGylating the surface to increase circulation times and reduce immediate clearance by the kidneys. The future of nanoparticle systems seems to be focused on further improving overall patient outcome by increasing delivery accuracy to the target area.