Self-Healing Hydrogel of Methotrexate-Loaded Nanoparticles Using Artocarpus heterophyllus Gum for Targeted Colon Cancer Therapy

Abstract

Background: Colon cancer remains a major cause of cancer-related morbidity and mortality worldwide, with conventional chemotherapy often hindered by poor specificity, systemic toxicity, and gastrointestinal degradation. Methotrexate (MTX), a widely used chemotherapeutic agent, suffers from limited oral bioavailability and non-targeted distribution. This study aimed to develop a pH-responsive, self-healing hydrogel system incorporating MTX-loaded PLGA nanoparticles using Artocarpus heterophyllus (jackfruit) seed gum for site-specific drug delivery to the colon. Methods: MTX-loaded nanoparticles were formulated using the double emulsion solvent evaporation technique and characterized for particle size and polydispersity. A self-healing hydrogel was prepared via solution casting, combining jackfruit seed gum, chitosan, and polyvinyl alcohol, crosslinked with glutaraldehyde. MTX-loaded nanoparticles were embedded into the hydrogel matrix. The system was evaluated for swelling behavior, mechanical strength, self-healing efficiency, drug release, and structural properties using SEM, FTIR, and XRD techniques.

Results: The developed nanoparticles exhibited a mean size of 85.6 ± 4.5 nm and a PDI of 0.15 ± 0.02. SEM revealed a porous hydrogel network with uniform nanoparticle distribution. FTIR confirmed successful chemical crosslinking and drug encapsulation, while XRD indicated drug amorphization within the matrix. The hydrogel demonstrated pH-sensitive swelling with a significantly higher swelling ratio at pH 7.4 (340% ± 10%) compared to pH 5.8 (200% ± 7%). Mechanical analysis showed a tensile strength of 0.80 ± 0.1 MPa and 90% ± 3% self-healing efficiency. In vitro release studies confirmed colon-specific release, with 90% MTX released over 8 hours at pH 7.4, following non-Fickian kinetics. Conclusion: The jackfruit gum-based self-healing hydrogel system effectively encapsulates and delivers MTX in a controlled, colon-targeted manner while offering mechanical resilience and biocompatibility. This platform holds promise as a sustainable, site-specific oral chemotherapy strategy for improved colon cancer management.