Injectable anticancer biodegradable hydrogel-based nanocomposites: Synergistic pH-responsive
Xiuxiu Li1, Weiyu Ma1, Zhou Xu1
1Department of Gastroenterology, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical University, No.3, Xinghualing District, Taiyuan, Shanxi 030001, China.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a cancer that is highly aggressive and has a challenging tumor microenvironment, which restricts the efficacy of conventional medical treatments. This investigation aims to formulate a localized anticancer hydrogel that incorporates a Paclitaxel/β-cyclodextrin (β-CD) nanocomplex composed of polyvinyl alcohol (PVA). Enhancements in drug delivery, therapeutic efficacy, adverse effects, and the mitigation of multidrug resistance are the objectives of PDAC treatment. In silico analyses were performed to examine the interaction between paclitaxel (PTX) and β-CD, which revealed favorable binding and pH-dependent release characteristics. Via FTIR and XRD analyses, the PTX/β-CD inclusion complex was verified. A hydrogel based on PVA was subsequently formed by incorporating this complex. The hydrogel's physicochemical and structural characteristics were examined using SEM, FTIR, XRD, and rheological methods.. Hydrogel's physical characteristics were evaluated through biodegradation and water absorption experiments. The cytotoxic and anti-metastatic potential of the hydrogel nanocomposite was quantified by conducting MTT assays and invasion and migration assays to assess its anticancer efficacy. The estimated adsorption energy (Eads) of PTX within β-CD to form the PTX/β-CD complex was -1.133 × 10-3 kJ/mol. In the Monte Carlo (MC) method, van der Waals forces and electrostatic interactions were considered based on group-based interactions with a cutoff radius of 12.5 Å. The interaction energy of B and PVA on PTX/β-CD was -319.150 kJ/mol. The binding energy (Ebinding = Einteraction) for B/PVA/PTX/β-CD was found to be -60.977 at pH 3.4 and -69.312 at pH 7.4. In acidic conditions, the Paclitaxel/β-CD nanocomplex exhibited efficient drug release and strong binding interactions. Biodegradation (80 % weight loss within 28 days) and water absorption (up to 500 % of its dried weight) were both exceptional characteristics of the PVA hydrogel. According to anticancer assays, the nanocomposite exhibited substantial cytotoxic effects, which included the inhibition of cancer cell migration and invasion. Paclitaxel's solubility and biological activity were significantly improved by the injectable hydrogel, which confirmed its potential as a sophisticated local drug delivery system. CONCLUSIONS: For the localized treatment of PDAC, the PVA-based injectable hydrogel that has been developed, which includes a Paclitaxel/β-CD nanocomplex, is a promising approach. Its targeted delivery, enhanced solubility, and potent anticancer characteristics offer a valuable method for enhancing therapeutic outcomes while reducing systemic side effects and multidrug resistance.
