Mucoadhesive Chitosome-Based Buccal Delivery of Goat Placenta-Derived Bioactive Macromolecules: Effects on 5-Fluorouracil-Induced Gingival Fibroblast Injury

Background/Objectives: Goat placenta extract (GPE), enriched with bioactive macromolecules, exhibits regenerative potential in both healthy and damaged cells. To enable targeted transport of these macromolecules to the buccal mucosa, potential delivery systems are required. The study aimed to evaluate the bioactivity of GPE on human gingival fibroblasts (HGFs) and to develop a GPE-loaded chitosome (CTS) mucoadhesive system for buccal delivery. Methods: The bioactivity of GPE was assessed in normal and chemotherapy-damaged HGF cells. GPE-loaded CTS was prepared, lyophilized, and then incorporated into an oral gel. The in vitro buccal deposition was visualized by confocal laser scanning microscopy. Results: GPE showed no cytotoxic effects at a concentration of 4000 µg/mL and significantly promoted the viability of both normal and 5-fluorouracil (5-FU)-treated HGF cells (p < 0.05). The GPE-loaded CTS formed nanosized vesicles and a positive surface charge, which may facilitate interactions with mucin. CTS and its loaded oral gel enhanced the delivery of macromolecular proteins into the buccal mucosa compared with gel alone. Conclusions: GPE promoted HGF viability and facilitated the recovery of 5-FU-induced gingival fibroblast injury. The CTS-loaded oral gel enhanced the buccal delivery of macromolecular protein, representing a promising strategy for oral mucosal regeneration and supportive care in chemotherapy-induced mucosal injury.