a Department of Biomedical Engineering, Division of Integrative Engineering, Chung-Ang University, 221 Heukseok-Dong, Dongjak-Gu, Seoul 156-756, Republic of Korea
b Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA
c Department of Mechanical Engineering and Materials Sceince, University of Pittsburgh, Pittsburgh, PA 15260, USA
d Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15260, USA
e Center for Complex Engineered Multifunctional Materials, University of Pittsburgh, Pittsburgh, PA 15261, USA
Received 4 August 2011. Revised 23 October 2011. Accepted 1 November 2011. Available online 12 November 2011.
Gene therapy has garnered much interest due to the potential for curing multiple inherited and/or increases in the acquired diseases. As a result, there has been intense activity from multiple research groups for developing effective delivery methods and carriers, which is a critical step in advancing gene delivery technologies. In order for the carriers to effectively deliver the genetic payloads, multiple extracellular and intracellular barriers need to be overcome. Although overcoming these challenges to improve the effectiveness is critical, the development of safe gene delivery agents is even more vital to assure its use in clinical applications. The development of safe and effective strategies has therefore been a major challenge impeding gene therapy progress. In this regard, calcium phosphate (CaP) based nano-particles has been considered as one of the candidate non-viral gene delivery vehicles, but has been plagued by inconsistent and low transfection efficiencies limiting its progress. There has been major research effort to improve the consistency and effectiveness of CaP based vectors. Currently, it is therefore thought that by controlling the various synthesis factors such as Ca/P ratio, mode of mixing, and type of calcium phosphate phase, such variability and inefficiency could be modulated. This review attempts to provide a comprehensive analysis of the current research activity in the development of CaP based ceramic and polymer-ceramic hybrid systems for non-viral gene delivery. Preliminary transfection results of hydroxyapatite (HA or NanoCaPs), amorphous calcium phosphate (ACP) and brushite phases are also compared to assess the effect of various CaP phases, and correspondingly, changes in the dissolution characteristic of the pDNA-CaP complex on the gene transfection efficiency.
