Exploiting tumour acidity for polymer based drug delivery

Whitty EG1,2,3, Castignolles P2, Gaborieau M2,3 and Callaghan R1

  1. Department of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, ACT, 0200, Australia.
  2. Australian Centre for Research on Separation Science (ACROSS), School of Science and Health, Western Sydney University, Parramatta, NSW, 2150, Australia.
  3. Medical Sciences Research Group, School of Science and Health, Western Sydney University, Parramatta, NSW, 2150, Australia.

An acidic micro-environment is a hallmark feature of solid tumours generated by metabolic adaptations including an increased reliance on glycolysis and its concomitant production of lactic acid. The acidic environment has deleterious effects on many anticancer drugs; however, several novel therapeutic strategies are beginning to exploit this property. Our consortium has developed three configurations of poly(sodium acrylate) (PNaA) as a pH-sensitive drug delivery system. Initial efforts have focussed on the anticancer drug cisplatin, which is beset with poor stability, toxicity and pharmacokinetic properties. Loading cisplatin onto a polymer may circumvent many of these issues by providing targeted delivery and increased stability. PNaA is loaded with cisplatin at pH9 and the attachment is stable, reversible and displays a pH-dependent release process. The three configurations of PNaA differ in their branching structure and thereby offer distinct loading capacities. In the present investigation we have undertaken preliminary characterisation of PNaA in a monolayer cell culture system. Unloaded polymers did not alter cell cycle progression nor where they associated with significant levels of apoptosis. Cisplatin loaded polymers displayed a greater potency than observed with free drug. The increase in drug potency demonstrates the viability of this polymer as a drug delivery system.