Synthetic strategy matters : the study of a different kind of PVP as micellar vehicles of metronidazole

Abstract

Poly(1-vinyl-2-pyrrolidone) (Povidone, PVP) is one of the most interesting and versatile synthetic polymers utilised in the pharmaceutical and cosmetic industries. Its large-scale commercial production offers an assortment of products in a wide range of molecular weights but poorly-controlled (macro)structural parameters (i.e., dispersity, functionality) limiting the efficiency of PVP-based drug delivery systems (DDS). In this work, synthesised linear and star-shaped PVPs with a strictly defined structure and functionality were compared with the linear, commercially-supplied product and explored as potential vehicles for physical entrapment of metronidazole (MTZ). Here, a question is addressed how differences in their macromolecular properties affect the amorphisation of MTZ, drug encapsulation, the stability of drug-loaded micellar structures and their in vitro release from the carrier. The X-ray diffraction studies and calorimetric measurements revealed that MTZ crystallises in all investigated herein systems reducing the glass transition temperature of the binary mixture significantly. Transmission electron microscopy and dynamic light scattering analysis revealed that MTZ-loaded DDS are able to form ultrasmall regular nanocarriers with an increasing effect of regularity and sphericity from star-shaped DDS to linear-based ones. We founded that synthesised linear-based DDS is the most effective for MTZ entrapment (PVP:MTZ = 1:1 weight ratio) due to their smallest hydrodynamic radius dh = 14.7 nm, the highest stability of micellar structures −2.37 mV, and the highest values of loaded drug 76.5%. Moreover, all applied PVP-based DDS revealed an initial burst release effect of MTZ (pH = 7.4) reaching up to 60% of drug released within the first 5 h (the first-order release model fits). The marked efficiency of MTZ-loaded DDS of strictly defined structural parameters indicates the great importance of polymer preparation strategy in the targeted therapy.