Fibrillar pharmacology of functionalized nanocellulose

Abstract

Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

M6A-mediated upregulation of circMDK promotes tumorigenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

“…6F). It is consistent with previous report that the liver can rapidly uptake, degrade, and eliminate NPs, while the kidneys could excrete nanoparticles through urine [29,30]. The tumor size and weights were also significantly suppressed by PAE-Cy5-siRNA complex (Supplementary Fig.…”

Cellular infiltration in an injectable sulfated cellulose nanocrystal hydrogel and efficient angiogenesis by VEGF loading

“…As described in the Background section, the biocompatibility of CNC itself and CNC hydrogel in vivo has been controversial and not been clearly reported. In most cases, CNC was used as an additive to hydrogel composites to improve their mechanical properties or as a gelation inducer [ 24 , 30 , 31 , 33 , 42 – 44 ], and the reports for biomedical applications and biocompatibility investigations of CNC itself are limited [ 45 ]. In this study, hydrogels composed of only CNCs were subcutaneously injected into mice to evaluate their in vivo biocompatibility, which is the most basic characteristic of a biomaterial scaffold.…”

“…However, in vivo evaluation of the biocompatibility of CNC itself and CNC-based hydrogel, not as an additive to other materials, has been rarely reported; the biocompatibility of a low concentration (0.5%) CNC suspension, not as a hydrogel, was compared with cellulose nanofiber [ 32 ]. Also, the biocompatibility and biodistribution of amine-functionalized CNC as a nanoparticle state after labeling with radioactive metal and fluorescent dye upon intravenous injection into mice were analyzed [ 33 ].…”

Nanocellulose, the Green Biopolymer Trending in Pharmaceuticals: A Patent Review

“…Despite the growing interest in nanocellulose, a mapping of patents has not been carried out so far. Academic reviews published so far have addressed the possibilities of using nanocelluloses for drug delivery in transdermal devices [ 12 , 13 , 14 , 15 ], as disintegrants or super disintegrants [ 16 ], for wound healing [ 17 , 18 , 19 ] and for injectables [ 20 , 21 , 22 ]. Furthermore, nanocellulose has also demonstrated its effectiveness in tissue engineering [ 19 , 23 , 24 ].…”

“…Hydrogel is the usual attained form of nanocellulose, and its purposes may range from wound healing [ 17 , 18 , 69 , 70 , 71 ] to part of the design for developing injectables [ 20 , 21 , 22 ]. Moreover, the tissue engineering field has developed promising research regarding nanocellulose [ 19 , 23 , 24 , 72 ].…”