Nanocellulose-based nanogels for sustained drug delivery: Preparation, characterization and in vitro evaluation

Polysaccharide-based nanocarriers such as nanogels have recently received considerable attention in modified drug delivery due to their biocompatibility and biodegradability. However, the application of the nanocarriers was limited due to longer preparation time, usage of large amounts of organic solvents and surfactants as well as lower drug loading capacity (LC) and encapsulation efficiency (EE). In this study, nanogels were prepared from carboxymethyl nanocellulose (CMNC)-lysozyme blends in aqueous phase via electrostatic interaction, a simple and surfactant-free approach, for sustaining drug release with better LC and EE. The nanogels were investigated in terms of size, polydispersity index (PDI), turbidity, colloidal and thermal stabilities, chemical functionality, morphology, crystallinity, LC, EE, and in vitro release patterns of different Biopharmaceutics Classification System (BCS) class drugs (acyclovir, carbamazepine, and furosemide). At pH 7.4 and above, nanogels remained in collapse state through strong electrostatic interaction between the polyelectrolytes, followed by the intra-molecular H-bonding for further reduction of the size of the nanogels. Spherical nanogels in the size of < 110 nm with PDI < 0.2, and large zeta potential ranging from-38 to-55 mV were prepared at optimal condition (at 1:1 wt ratio of CMNC:lysozyme, heating temperature and time: 75 C and 30 min, pH 7.4). The size and PDI of the nanogels were significantly affected by the weight ratios of CMNC-lysozyme, pH, sonication and heating times (p < 0.01), but not much affected by drug loading and storage conditions. The nanogels demonstrated high EE (62-94%) and LC (18-27%), and sustained release (48-80%) profiles of the model drugs over 12 h. These results suggest that the synthesized nanocellulose-based nanogels following easy and green preparation approach exhibited attractive properties with respect to the size, PDI, zeta potential, shape, thermal stability, EE, LC, and versatility for encapsulating and sustaining different BCS class drugs.