Pollen microgels as functional building blocks in a thermosensitive chitosan-based in situ gel for dual-responsive controlled drug delivery

In situ gels offer important advantages for localized drug delivery but often suffer from rapid gelation and suboptimal physicochemical properties. Pollen microgels (PMs) have emerged as naturally derived biomaterials with intrinsic microencapsulation capability, mucoadhesive potential, and pH-responsive behavior; however, their dense and pasty consistency limits their practical applicability. Here, date palm pollen (DPP) microgels were integrated into a thermosensitive chitosan-poloxamer (CS-PX) in situ gel to develop a dual-responsive composite delivery platform. The DPP microgel preparation method demonstrated efficient removal of intracellular contents while preserving the bilayered pollen structure, with only 3.35 ± 0.51% residual protein. A rehydration-based strategy exploiting the intrinsic reabsorption capacity of freeze-dried PMs was developed to enable controllable drug loading. Drug-release and kinetic studies demonstrate that DPP microgels exhibit a more sustained release profile than the CS-PX gel, while their incorporation into the thermosensitive matrix further prolongs release, indicating the formation of a dual-barrier delivery system. Moreover, the pH-responsive release behavior of the PMs was retained after incorporation into the hydrogel network. Increasing DPP microgel content extended gelation time from approximately 10 to 40 s, improved spreadability, and modulated rheological, textural, and microstructural properties of the CS-PX matrix. Additionally, the CS-PX gel overcomes the inherent pasty nature of PMs, improving their biomedical applicability. Besides, cytocompatibility studies using L929 fibroblasts confirmed the biocompatibility of the developed composite. Overall, this work demonstrates how this integration combines the functionalities of each component while addressing their limitations and offers a dual-responsive controlled drug delivery platform with tunable properties for multiple administration routes.