Injectable Biocompatible Hydrogels from Cellulose Nanocrystals for Locally Targeted Sustained Drug Release

Abstract

Injectable hydrogels from biocompatible materials are in demand for tissue engineering and drug delivery systems. Here, we produce hydrogels from mere cellulose nanocrystals (CNCs) by salt-induced charge screening. The injectability of CNC hydrogels was assessed by a combination of shear and capillary rheology, revealing that CNC hydrogels are conveyed via plug flow in capillaries allowing injection with minimal impact on mechanical properties. The potential of CNC hydrogels as drug carriers was elaborated by the in vitro release of the model protein bovine serum albumin (BSA), poorly water soluble tetracycline (TC), and readily soluble doxorubicin (DOX) into physiological saline and simulated gastric juice. For TC, a burst release was observed within 2 days, whereas BSA and DOX both showed a sustained release for 2 weeks. Only DOX was released fully from the hydrogels. The different release patterns were attributed to drug size, solubility, and specific drug–CNC interactions. The biocompatibility of CNC hydrogels and maintained bioactivity of released DOX were confirmed in a HeLa cell assay. The drug release was modulated by the incorporation of sucrose or xanthan gum in CNC hydrogels, whereas altering CNC concentration showed minor effects. The release into simulated gastric juice at pH 2 ceased for BSA due to charge inversion and electrostatic complexation, but not for smaller TC. Thus, CNC hydrogels may act as pH-responsive delivery systems that preserve drugs under gastric conditions followed by pH-triggered release in the duodenum.

Surface Interactions between Bacterial Nanocellulose and B-Complex Vitamins

“…Plots of Figure 4 show that at a pH of 2 there is no vitamin delivered. When the pH is changed to 7, the structure of the BNC web is opened, allowing for delivery [ 39 ]. This also confirms that we can modulate the release of the vitamins with a change in the pH conditions, which is related to the trajectory that this would follow in normal digestion.…”

Prevention of Prosthetic Joint Infection: From Traditional Approaches towards Quality Improvement and Data Mining

“…Several studies have demonstrated that collagen [157], hydrogel [158,159], or mineral [160] carriers of antibiotics and non-antibiotic agents (e.g., chitosan, antimicrobial peptides) are quite effective in vitro and even in vivo. However, the evidence for using such alternative antimicrobial carriers in preventing PJI remains to be demonstrated in clinical studies.…”

Recent Advances in Injectable Hydrogels for Controlled and Local Drug Delivery

“…[123] Some recent studies have applied supramolecular methods for generating injectable hydrogels for pH-triggered drug delivery. [106,[124][125][126] Supramolecular hydrogels are usually fabricated by crosslinking polymers with supramolecular noncovalent interactions, including hydrophobic or ionic interactions, inclusion complexation, or metal-ligand coordination. These hydrogels are stimuli responsive, injectable, have excellent biocompatibility, and can be loaded with bioactive molecules and proteins.…”