ABSTRACT
Infusate backflow or leak-back along the cannula track can occur during intraparenchymal infusions resulting in non-specific targeting of therapeutic agents. The occurrence of backflow depends on several variables including cannula radius, infusate flow rate, and tip location. In this study, polymer coatings that swell in situ were developed and tested with in vitro hydrogel experiments for backflow reduction. Coatings were applied to the external cannula surface in a dual layer arrangement with a poly(vinyl alcohol) outer layer atop an inner poly(ethylene oxide) and alginate layer. Once these coated cannulas were inserted and allotted an 8-10 min waiting period for hydration, backflow during infusions of 4.0 µl of a macromolecular tracer (Evans Blue labeled albumin) was reduced significantly under flow rates of 0.3-0.6 µl/min, allowing for more effective distribution within targeted regions. Polymer coating thicknesses before and after hydrations were 0.035 and 0.370 mm, respectively. Also, backflow data was fit to a model to estimate the effective local compressive stress caused by the hydrated polymers. After withdrawal of the cannula from the insertion site, the hydrated polymer coatings remained within the cavity left in the hydrogel tissue phantom and formed a seal at the infusion site that prevented further backflow during needle withdrawal. Ex vivo infusions in excised porcine brain tissues also showed significant backflow reduction while also demonstrating the ability to leave a polymer seal in the tissue cavity after cannula removal. Thus, application of these polymers as needle or cannula coatings offers a potentially simple method to improve targeting for local drug delivery.
