5.2 Solid lipid nanoparticles delivering gene

The fibrous scars occurring in the liver due to the increased production and deposition of hepatic extracellular matrix (ECM) components are called liver fibrosis reduce the physiological performance of the liver. Hepatitis viral infection is one of the major reasons for liver fibrosis and cirrhosis. Administration of antifibrotic therapeutics (e.g. connective tissue growth factor (siRNA) responsible for the cellular and molecular basis of fibrogenesis) is one of the most preferable approaches for the treatment of liver fibrosis. The siRNA loaded cationic SLNs (cSLNs) were developed by gently mixing CSLNs with siRNA at various weight ratios of cSLN to siRNA in 0.1 M PBS (pH 7.4) and then incubated at room temperature for 15 min. Naturally obtained low-density lipids (LDLs) were used in the preparation. The developed cSLN were able to silence the targeted gene in the presence of serum with notably low cytotoxicity. The cSLNs were PEGylated which were hydrodynamically stable and were able to protect their siRNA cargo from nuclease degradation during systemic circulation. The developed cSLNs loaded with siRNA administer through intravenous route delivered siRNA exclusively to the liver and resulted in a considerable reduction in collagen content and pro-fibrogenic factors with spectacular progress of pathophysiological symptoms in a liver fibrosis rat

model. Biodistribution study revealed site-specific delivery and accumulation of siRNA loaded cSLNs to the liver tissues [50].
