Design of pH-responsive Nanocarriers for Controlled Delivery ofAnti-allergic Corticosteroid Analogues

INTRODUCTION: Allergic inflammation has become an important public health issue. If left uncontrolled, it can lead to serious health problems. Mast cells and the drugs that regulate the endosomal compartments in these cells have become central to addressing these problems. The aim of this project was to build a biological model capable of regulating the intracellular delivery of anti-allergic corticosteroids. METHODS: The nanocarrier was designed based on micellar swelling and pH-responsive acid-sensitive linkers. The model's functionality was evaluated through a range of physicochemical characterization and in silico tests. Mathematical modeling was incorporated to simulate the nanocarrier's behavior and diffusion control. Models representing mucosal and mast cell-relevant environments were used to evaluate the designed system in a simulated microenvironment. RESULTS: The nanocarriers showed clear micellar swelling and a pronounced positive surface charge, with high drug encapsulation efficiency, and displayed both pH- and time-dependent behavior, as supported by physicochemical characterization and computational modeling. Mathematical modeling showed that charge dissolution was controlled and that drug release was governed by the rate of proton-dependent drug degradation. The system exhibited minimal drug release under physiological pH conditions, ensuring stability, while enabling controlled and enhanced drug release under acidic conditions relevant to mast cell-associated microenvironments. The system has low hemolysis, low cellular epithelial cytotoxicity, prolonged drug diffusive release, and favorable diffusive release. DISCUSSION: The collected data confirm that the design enables both time- and space-controlled release of the drug from the nanocarrier system within endolysosomal compartments associated with the allergic inflammatory response. The noted control of mast cell secretions illustrates immunomodulation and the control of side effects from systemic/extended use of corticosteroids. CONCLUSION: This study demonstrates that the system is not only safe and effective for the delivery of drugs into cells but also capable of targeting cells involved in the allergic inflammatory pathway. The emerging pH-sensitive nanocarriers have strong therapeutic potential.