Drug-polyionic block copolymer interactions for micelle formation: physicochemical characterisation

While covalent attachment of small drug molecules to AB copolymers for the formation of polymeric micelles for drug delivery has been investigated, fe w studies have focused on non-covalent interactions. The aim of this study was therefore to explore the potential of non-covalent interactions between an AB copolymer, Poly(aspartic acid)-poly(ethylene glycol) (Pasp-PEG), wit h anionic pendant groups and diminazene aceturate, a small molecular weight cationic drug. Micelles were prepared by mixing solutions of Pasp-PEG and diminazene in 25 mM Tris-HCl buffer. At all Pasp-PEG concentrations studied , the micelles appeared to be water soluble with a unimodal size distributi on and ranged in size from approximately 22 to 60 nm. The polyionic micelle s also displayed similar and small absolute zeta potential values at variou s drug:monomer molar ratios which confirmed stabilisation by the PEG corona . The scattering intensity was maximal and remained unchanged, while partic le size increased slightly at pH range from 3.4 to 7.2. At this pH range bo th the polymer and drug would be ionised and ionic interactions possible to drive micellar formation. An increase in size and scattering intensity wit h addition of NaCl to the micelles was attributed to dehydration of the PEG corona which may have led to aggregation of the micelles. The absence of m icellar dissociation upon addition of salt was attributed to the dominance of hydrogen bonding between Pasp and diminazene aceturate, as assessed by i sothermal titration microcalorimetry. Morphological evaluation of these con structs showed them to be discrete and fairly uniform in size and shape. Th is study was therefore successful in confirming the potential of non-covale nt interactions using an AB copolymer to form polyionic micelles for drug d elivery. (C) 2001 Elsevier Science B.V. All rights reserved.