Development of nanocellulose-based hydrogels for pharmaceutical and biomedical applications

Abstract

Nanocellulose, derived from plants, is a sustainable material with a nanostructured composition. It exhibits a significant characteristic of high flexibility, biocompatibility, non-toxicity, and biodegradability. Moreover, the desirable properties, including surface area, pore size, and mechanical properties can be modified through various extraction and surface modification techniques applied to nanocellulose. Consequently, it is utilized in various fields, such as engineering, material reinforcement, packaging, drug delivery systems, bioactive compounds, food, pharmaceuticals, and biomedical applications. In this research, cellulose nanofibers were developed and prepared for the fabrication of hydrogels to enhance the properties of the hydrogel in order to achieve the desired characteristics. After that, the evaluation of the hydrogel properties was conducted, including its morphology, mechanical strength and flexibility, gel content, swelling behavior, drug content, in vitro drug release profile and kinetic, biocompatibility study, and antimicrobial activity, which are essential for pharmaceutical and biomedical applications. This is a pathway to enhance value and actively promote environmentally conscious green business management model, thereby facilitating the progress of a sustainable and integrated society. In the first study, hydrogel formulations were fabricated by combining cellulose nanofibers (CNFs, C), low-methoxyl pectin (LMP, P), and sodium alginate (SA, A) at different mass ratios. Subsequently, the hydrogel was crosslinked using 3% w/w calcium chloride (Ca), 0.5 M citric acid (Ci), or a combination of 0.5 M citric acid with 3% w/w calcium chloride (Ca+Ci). The clindamycin hydrochloride was selected as the drug model to determine drug content and in vitro drug release profile and kinetic. Our results indicated that a hydrogel composed of CNFs/LMP/SA at a mass ratio of 2:0.5:0.5, crosslinked with Ca+Ci, exhibited suitable properties and showed biocompatibility with human keratinocyte cells (HaCaT). The hydrogel demonstrated a clindamycin hydrochloride content more than 80%. In vitro drug release data revealed a prolonged release profile, with a cumulative drug release percentage extending up to 3 days. This innovative hydrogel formulation shows potential for pharmaceutical applications as a transdermal drug delivery system, offering prolonged drug release for the treatment of infected wounds. However, in first study, the production of the hydrogel required the incorporation of polyethylene glycol (PEG) to enhance the dispersion of CNFs in water. To produce hydrogels with desired properties, it is necessary to mix it with other polymers. Using only CNFs for hydrogel production presents difficulties and challenges. In the second study, our objective aimed to improve the dispersion of CNFs by conducting oxidative modification on the surface of CNFs. This modification increased the presence of carboxyl groups within the CNF structure, resulting in enhanced dispersion in water. Following the assessment of the physicochemical properties, carboxylated cellulose nanofibers (c-CNFs) were obtained and used in the fabrication of polyhexamethylene biguanide (PHMB) nanocellulose hydrogels through a physical crosslinking technique. These hydrogels have been developed for antimicrobial applications in the pharmaceutical and biomedical fields. The results demonstrated that the 7% c-CNFs-2h formulation, loaded with PHMB, exhibited optimal characteristics in terms of morphology, porosity, mechanical strength, gel content and swelling behavior. Additionally, it retained over 80% of the PHMB drug content. in vitro drug release data indicated a prolonged release pattern up to 3 days. In a noteworthy achievement, this study has successfully formulated a hydrogel using only CNFs. The formulation demonstrated antimicrobial efficacy and excellent potential for pharmaceutical and biomedical applications.