Process engineering of doxorubicin-loaded ZIF-8 / phase-change material core–shell microparticles by coaxial electrospray for dual pH- and temperature-triggered release

Designing stimuli-responsive carriers that combine the pH-sensitivity of a metal–organic framework (MOF) with the thermal switching of a phase-change material (PCM) requires careful control of the materials process, not only of the materials themselves. Here we report a coaxial-electrospray process that converts a doxorubicin (Dox)-loaded zeolitic imidazolate framework-8 (Dox@ZIF-8) core into a Dox@ZIF-8@PCM core–shell microparticle, using a 4:1 lauric acid/stearic acid (LASA) eutectic with a melting peak near 39 °C as the temperature-triggered shell. Two systematic process studies were carried out. First, the one-pot Dox encapsulation step was tuned across three Dox feed concentrations (0.5, 1.0, and 6.0 mg mL −1 ), yielding drug loading content of 0.47%, 1.44%, and 3.68%, with particle diameters that decreased from 354 to 210 nm and morphologies that shifted from rhombic dodecahedral toward more spherical as Dox content fell. Second, the outer LASA flow rate of the coaxial electrospray was varied across six set-points from 0.4 to 0.75 mL h −1 , identifying 0.65 mL h −1 as the operating point that produces uniform, fiber-free spherical shells of ∼54% PCM content. SEM, XRD, FTIR, DSC, and TGA confirmed that the ZIF-8 framework is retained through encapsulation and that LASA forms a continuous shell with a 38.1 °C melting temperature. In vitro release showed a 76% pH-driven contrast (pH 4.0 vs. 10.0) and a 62% temperature-driven contrast (40 °C vs. 37 °C). The work establishes a process window for transferring this dual-stimuli platform from a model dye to a clinically relevant active pharmaceutical ingredient.