Linear polyphosphates (PP), and in particular the coacervates that can be formed through subsequent cationic interactions, represent an interesting class of biomaterials for biomedical device development. Such coacervates have potential utility in a variety of clinical applications, including embolization procedures that may be used to block blood flow to tumors, or in localized drug delivery by way of microencapsulation. In this presentation, detailed studies on the processing and resulting physical properties of polyphosphate coacervate systems derived from NaPP and divalent cations – namely calcium, strontium and barium – are described in relation to targeted device optimization. Generally speaking, these polyphosphate coacervates degrade and dissolve at a fast rate, losing half of their original mass in a week and transforming to mainly pyrophosphate after 4 weeks. This burst dissolution phase occurs earlier for coacervates prepared from very short chain polyphosphate, although longer polyphosphate chains do not increase coacervate longevity significantly. In contrast, cation type and NaPP degree of polymerization (Dp) can be shown to profoundly impact viscoelastic properties, with high Dp yielding predominantly elastic characteristics; high Dp coacervates also demonstrate generally greater hemostatic properties overall. Using a design of experiments approach, a radiopaque liquid embolic agent synthesized from Ca(Ba,Sr)PP coacervates was optimized with respect to viscosity, radiopacity and cell viability, and subsequently validated in an animal model. Efforts to enhance the overall versatility of these coacervate-based systems through processing modifications are also described. Initial studies have revealed that introducing low levels of trivalent ions (Ga, Al) can modulate the degradation and cohesive characteristics of these in situ forming CaPP coacervates. Using polyphosphate coacervate precursors, a low temperature emulsion / solvent extraction technique has also been employed to generate therapeutically loaded phosphate glass microspheres. Sustained in vitro release of minocycline over a 7-day period was observed, suggesting potential utility of this approach for treating periodontitis. Overall, PP coacervate-derived biomaterials offer potentially innovative solutions to challenging clinical applications.

Design and optimization of polyphosphate coacervates for use in biomedical devices

253rd National Meeting (2017)

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