Reversible pH-Sensitive Chitosan-Based Hydrogels. Influence of Dispersion Composition on Rheological Properties and Sustained Drug Delivery

Abstract

The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS) for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA); they were characterized by Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MTDSC) and scanning electron microscopy (SEM), and their rheological properties were studied. To the best of the authors’ knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS) and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking) revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa), as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%). Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.

Nanostructured Chitosan-Based Biomaterials for Sustained and Colon-Specific Resveratrol Release

“…The influence of the dispersion composition on its rheological properties was evaluated. The release profiles of a model drug, diclofenac sodium (DCNa) as well as their relationships with polymer concentration, drug loading and degree of cross-linking were established [53]. Based on this study, we have carried out the preparation of CTS-based bioadhesive hydrogels with RES-loaded NP embedded into their structure.…”

“…As SEM has proved to be a particularly relevant technique to determine the scaffold characteristics (pore size and morphology) of hydrogels and biological systems, some SEM images were obtained in order to study the microstructure of the composites formed. To preserve the skeleton structure of our systems prior to SEM observations, the freeze dried method previously reported for cells has been used [53,55,56]. Figure 5 compares SEM micrographs of the chitosan-based hydrogels with RES-loaded Xr and non-Xr NPs.…”

“…Firstly, the NPs (cross-linked and non-cross-linked) were loaded with RES under the optimized conditions disclosed in the experimental design described above: RES/polymer ratio: 0.75; temperature: 39 °C, loading time: 24 h. Secondly, the hydrogel preparation was conducted similarly to the procedure recently described by us [53] that can be summarized as follows: CTS (0.4 g, 1.74 mmol of free amine groups) was charged in a round-bottom flask provided with a stirrer bar; then, an aqueous solution of tricarballylic acid (1.02 mL, 10 mg/mL, 0.05 mmol), a solution of acetic acid (0.1 mL, 52% w / v ), a dispersion of resveratrol-loaded NPs (5.5 mL, RES 0.9375 mg/mL) and double-distilled water [up to a final weight of 10 g (final polymer concentration: 4% w / w )] were added in sequence. The mixture was stirred to homogenization at 40 °C during 1.5 h. The solution was cooled at 25 °C and the stirring proceeded overnight at 25 °C.…”

Nonlinear sensors for biomaterials—Principles and applications

“…Both processing protocols yielded wires having widely separated two-step transformations from martensite to austenite involving the interme- The special ability of TMDSC to provide increased information about polymer transitions has resulted in its use by several other research groups to investigate biomedical materials. Studies have reported the formation of dextran hydrogels by crystallization (Stenekes, Talsma, & Hennink, 2001), observed the polymer transitions at different heating rates for dental mouth guard materials (Meng et al, 2007) characterized thermoresponsive hydrogel copolymers designed for medical device applications (Jones, Lorimer, McCoy, & Gorman, 2008), analysed biomaterials derived from silk fibroin-hyaluronic acid hydrogels (Hu, Lu, et al, 2010) and silk-tropoelastin protein systems (Hu, Wang, Rnjak, Weiss, & Kaplan, 2010), investigated ultrasonication-induced and naturally self-assembled silk fibroin-wool keratin hydrogel biomaterials (Vu et al, 2016), characterized reversible pH-sensitive chitosan-based hydrogels (Iglesias, Galbis, Valencia, De-Paz, & Galbis, 2018) and assessed the use of a multifunctional monomer as a co-initiator and crosslinker to provide strengthening with enhanced hydrolytic stability for dental adhesives (Song et al (2020). Righetti (2017) has published a review article about the complexity of the crystallization process for polymers, with comments about the phenomena of "reversing" and "reversible" melting.…”

Development of a Lidocaine-Loaded Alginate/CMC/PEO Electrospun Nanofiber Film and Application as an Anti-Adhesion Barrier

“…Therefore, the control of crosslinking density is generally used to regulate the physical properties of polymers, such as drug release profiles. Numerous studies have been conducted on the regulation of drug release behavior by controlling the degree of crosslinking of drug carriers [31][32][33]. Scheme 1.…”