Effect of the temperature of biomixing on the pH/temperature sensitive controlled drug release of a chitooligosaccharide-based hydrogel

Abstract

Chitooligosaccharide (COS)–carboxymethyl cellulose (CMC)–polyethylene glycol diacrylate (PEGDA) hydrogel was fabricated through bio-ink mixing at two different temperatures (4 °C and 30 °C) to investigate its drug release performance in gastric and intestinal fluid conditions. The polyelectrolyte complex was transformed into a hydrogel through UV crosslinking using Irgacure 2959 as the photoinitiator. Vancomycin hydrochloride (COVAN) was loaded into the hydrogel solution by mixing it. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were done to characterize the two different hydrogels with and without the drug. The hydrogels exhibited pH and temperature-responsive swelling behavior. The equilibrium swelling ratio for both the drug-free hydrogels was highest at 6.8 pH and 37 °C, having a value of ∼1000%, and the lowest at 1.2 pH at 450–650%. 4°(D)-drug-incorporated hydrogel mixed at 4 °C showed the highest release in intestinal fluid conditions at 37 °C with around 98% of the total drug released after a day. 4°(D) showed higher drug release in a sustained manner at 1.2 pH, 37 °C, but lower drug release at 1.2 pH, 30 °C compared to N(D) (drug incorporated regular hydrogel mixed at 30 °C). The drug release data fit into the Korsmeyer–Peppas model, where the n value indicated a Fickian drug transport in most cases. 4°(D) showed higher drug release and higher drug incorporation compared to N(D) under most conditions. 4°(D) also showed a greater inhibitory effect against Gram-positive bacteria B. cereus, lower minimum inhibitory concentration (MIC), and lower minimum bactericidal concentration (MBC) compared to N(D). Therefore, altering the temperature of mixing of the hydrogel solution has the potential to improve the drug delivery systems and achieve better therapeutic value. In this case, 4°(D) has potentially greater efficacy than N(D) as a bactericide for various Gram-positive bacteria. This study also establishes biomixing temperature as a significant parameter for the future treatment of colonic diseases such as Crohn's disease, ulcerative colitis, etc.