Interaction of N-(2-hydroxypropyl)methacrylamide based homo, random and block copolymers with primary immune cells.

Abstract

Polymer nanoparticles (NP), e.g., polymeric micelles, represent a promising platform for drug delivery including the field of immune modulation. In respect to this potential application, identification of chemical and structural properties that affect interaction of polymers with immune cells is an important step in their preclinical characterization. A series of well-defined, fluorescently labeled homopolymers, random as well as block copolymers based on the clinically approved N-(2-hydroxypropyl)methacrylamide (HPMA) were prepared to study the influence of polymer architecture on the interaction of polymers with primary human und murine immune cells systematically. The number average of the molar mass (M(n)) for all polymers was set to the range of 4-14 kDa with a varying ratio of hydrophilic and hydrophobic units and dispersities (D) in the range of 1.17-1.29. Cell uptake greatly depended on the polymer molecular weight and micro structure: Comparison of polymers of the same molar mass but varying ratio of hydrophilic and hydrophobic units revealed a strict dependency of cellular uptake on the size of the hydrophobic block. HPMA-ran-LMA copolymers with high amounts of lauryl side chains (15 and 20% LMA content) had highest internalization rates into human and mouse immune cells (monocytes, granulocytes, B and T cells). Our findings underline the role of particle size and composition of polymeric carriers in the field of nanomedicine.