Effects of block copolymer properties on nanocarrier protection from in vivo clearance and targeting

S.M. D’Addioa, W. Saada, S.M. Ansellb, J.J. Squiersa, D. Adamsona, M. Herrera-Alonsoa, A. Wohlc, T.R. Hoyec, C.W. Macoskod, L.D. Mayerb, C. Vauthiere, R.K. Prud’homme
Princeton University, US

Keywords: nnoparticle, targeting, clearance, block copolymer

Summary:

Drug nanocarrier clearance by the immune system must be mitigated in order to achieve targeted delivery to pathological tissues. To evaluate the possibility for successful targeting and drug delivery, there is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we have produced hydrophobic nanocarriers with dense PEG layers resulting from block-copolymer-directed assembly during rapid precipitation. Nanocarriers were formed using block copolymers with hydrophobic anchor blocks of polystyrene (PS), poly-ε-capralactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with various molecular weights, from 1.5 kg/mol to 9 kg/mol. In vitro complement activation assays were conducted in an effort to correlate the protection of the nanocarrier surface from complement binding and activation and in vivo circulation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly were proposed, relating to the relative size of the hydrophilic and hydrophobic block, the hydrophobicity of the anchoring block, and the absolute size of the PEG block.