pH-Responsive Biocomposite System for Controlled Drug Delivery

Surgical removal of malignant tumors often leaves behind residual cells that are difficult to eliminate without adverse side effects from conventional therapies. This is one of the challenges driving the development of targeted drug delivery systems that offer the potential for precise, localized treatment, thus reducing the required medication dosage and minimizing damage to healthy tissues. One promising strategy for such targeted treatment involves leveraging pH differences between healthy tissue (pH 7.35-7.45) and tumor environments (pH ~6.8). This study aims to develop a pH-selective hydrogel patch capable of controlled, sustained drug release at tumor sites to address the challenge of residual tumor cells post-surgery. The pH-sensitive rate of drug release from the biocomposite could also be applied in wound healing and bone repair, where pH differences are similarly important. Our proof-of-concept study utilizes an alginate hydrogel host combined with an amorphous CaCO3 (ACC) matrix. Alginate's excellent biocompatibility and tunable physical properties make it an optimal test material, while ACC, a biocompatible sparingly soluble salt, allows efficient drug loading and provides additional control over drug release rates.

The biocomposite material is designed to be placed directly at a tumor site post-surgery, where the ACC dissolves faster in the lower local pH conditions of the tumor environment, delivering medication at a controlled and enhanced rate. This specificity to the tumor's acidic environment allows for a higher local drug concentration at the target site, improving treatment precision and reducing systemic exposure. In the experimental procedure, ACC was synthesized and integrated into the alginate matrix. The rate of ibuprofen release was measured spectrophotometrically against a standard curve for both control (ACC only) and hydrogel-hosted (ibuprofen-loaded ACC) conditions. The tests confirmed efficient encapsulation of ibuprofen by the ACC and demonstrated the ability of the biocomposite to release the drug in a controlled manner.

The drug release rate from the alginate hydrogel with incorporated CaCO3 was particularly stable and gradual in acidic pH environments similar to those found at tumor sites. Optimizing the alginate formulation further improved structural stability, consistency, and the drug release profile, addressing the challenge of maintaining an effective drug concentration at the site of interest over an extended period. Future directions will focus on tuning the concentration of ACC within the alginate matrix to maximize drug loading efficiency and ensure stable, long-term drug release. Additionally, we will examine other model drugs with solubility and hydrophobicity properties that approximate those of therapeutics used for localized treatments. This pH-responsive biocomposite system shows promise for controlled drug delivery in tumor environments, potentially improving the efficacy of post-surgical cancer treatments while minimizing side effects.