Thus, DP PLys can control the dynamic stability of uPICs, i.e., the balance between K a and blood concentration of free bPEG-PLys. A smaller DP PLys resulted in a lower K a and a longer blood retention time of free bPEG-PLys. Importantly, DP PLys significantly affected the association constant of bPEG-PLys to siRNA ( K a) and blood retention of free bPEG-PLys.
Under bPEG-PLys-rich conditions, the hydrodynamic diameters of uPICs were 15–20 nm, which were comparable to that of the bPEG block (i.e., ∼18 nm). Structural analyses revealed that the uPIC size and association numbers were mainly determined by the molecular weights of PEG and DP PLys, respectively. These bPEG-PLys were then evaluated in physicochemical characterization and pharmacokinetic analyses. We prepared a series of bPEG-PLys with DP PLys values of 10, 13, 20, 40, and 80 for the uPIC formation and siRNA with 40 negative charges. Herein, we examined how the degree of polymerization of PLys (DP PLys) affected the dynamic stability of uPICs in the bloodstream during prolonged circulation. The blood retention time of uPICs is dramatically increased in the presence of free bPEG-PLys, suggesting dynamic stabilization of uPICs by free bPEG-PLys based on their equilibrium. To stabilize small interfering RNA (siRNA) in the bloodstream for systemic RNAi therapeutics, we previously fabricated ultrasmall siRNA nanocarriers that were sub-20 nm in hydrodynamic diameter, named as unit polyion complexes (uPICs), using two-branched poly(ethylene glycol)- b-poly( l-lysine) (bPEG-PLys).
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