Nanocellulose hydrogels as bio-interface analogs for studying nanomaterial transport and accumulation

Abstract

Nanoparticles have been proposed as drug delivery vehicles to enhance targeting and efficiency of traditional and novel therapeutics. Previous studies have identified size, surface charge, and volume exclusion as factors that influence nanoparticle diffusion and retention. However, there is little accepted or successful quantification of how these parameters influence nanoparticle penetration relative to biological adaptation and biological response. Part of the challenge is the response of living biological interfaces to many of these nanoparticle delivery vehicles and nanosized drugs. This study aimed to emulate key physicochemical barriers to diffusion found in living biomaterials by developing a tunable, synthetic hydrogel. Through the controlled exposure of 150 kDa and 2 MDa nanodextrans with neutral and negative surface charge, we evaluated the system's ability to emulate three core physicochemical features often implicated in biofilm-associated transport resistance: size exclusion, charge interactions, and volume exclusion. We demonstrated a 30% statistically significant decrease in partition coefficients for 2 MDa nanodextran from 150 kDa nanodextran, confirming the ability of the nanocellulose-based microcaps to size based exclusion of hydrated biomaterial matrices. We combined our results with bioaccumulation data from the literature and found only the interaction of size and charge had a statistically significant effect (p-value < 0.05, F-statistic = 4.8). This controllable system can be coupled with in silico modeling to understand interfacial transport phenomena for nanomaterial-biomaterial interactions.

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