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Pulmonary drug delivery via microspheres has gained growing interest as a noninvasive method for therapy. However, drug delivery through the lungs via inhalation faces great challenges due to the natural defense mechanisms of the respiratory tract, such as the removal or deactivation of drugs. This study aims to develop a natural polymer-based microsphere system with a diameter of around 3 μm for encapsulating pulmonary drugs and facilitating their delivery to the deep lungs. Pectin was chosen as the foundational material due to its biocompatibility and degradability in physiological environments. Electrospray was used to produce the pectin-based hydrogel microspheres, and Design-Expert software was used to optimize the production process for microsphere size and uniformity. The optimized conditions were determined to be as follows: pectin/PEO ratio of 3:1, voltage of 14.4 kV, distance of 18.2 cm, and flow rate of 0.95 mL/h. The stability and responsiveness of the pectin-based hydrogel microspheres can be altered through coatings such as gelatin. Furthermore, the potential of the microspheres for pulmonary drug delivery (i.e., their responsiveness to the deep lung environment) was investigated. Successfully coated microspheres with 0.75% gelatin in 0.3 M mannitol exhibited improved stability while retaining high responsiveness in the simulated lung fluid (Gamble’s solution). A gelatin-coated pectin-based microsphere system was developed, which could potentially be used for targeted drug delivery to reach the deep lungs and rapid release of the drug. 

The development of vascularized tissue is a substantial challenge within the field of tissue engineering and regenerative medicine. Studies have shown that positively-charged microspheres exhibit dual-functions: (1) facilitation of vascularization and (2) controlled release of bioactive compounds. In this study, gelatin-coated microspheres were produced and processed with either EDC or transglutaminase, two crosslinkers. The results indicated that the processing stages did not significantly impact the size of the microspheres. EDC and transglutaminase had different effects on surface morphology and microsphere stability in a simulated colonic environment. Incorporation of EGM and TGM into bioink did not negatively impact bioprintability (as indicated by density and kinematic viscosity), and the microspheres had a uniform distribution within the scaffold. These microspheres show great potential for tissue engineering applications.