Sea Cucumber-Derived Frondoside A for Colorectal Cancer Therapy: Production, Functionalization, and Colon-Targeted Delivery Using pH-Responsive Microcapsules

This review examines a marine-biopolymer-enabled strategy for the colon-targeted delivery of Frondoside A, a sulfated triterpene glycoside obtained from Cucumaria frondosa, for colorectal cancer (CRC) therapy. Particular attention is given to marine and naturally derived polysaccharides—including chitin, chitosan, alginate, carrageenan, fucoidan, and related materials—as functional carriers for protecting Frondoside A during gastrointestinal transit and controlling its release in the colon. The review connects marine biomass sourcing and bioactive-compound production with polymer extraction, deacetylation, purification, physicochemical characterization, and formulation. Current evidence indicates that Frondoside A can induce mitochondrial and caspase-dependent apoptosis, inhibit proliferation, migration, and invasion, modulate inflammatory pathways, and enhance the activity of 5-fluorouracil and oxaliplatin under preclinical conditions. Oral translation remains constrained by uncertain gastrointestinal stability, variable transit, premature absorption, and potential systemic toxicity. Chitosan–alginate polyelectrolyte complexes and other polysaccharide-based microcapsules offer a plausible functionalization platform because polymer charge, molecular weight, degree of deacetylation, crosslinking density, and coating architecture can be adjusted to influence gastric protection, swelling, mucoadhesion, and release kinetics. However, direct evidence from Frondoside A-loaded colon-targeted formulations remains limited. Future work should integrate standardized marine sourcing and extraction, polymer and payload characterization, encapsulation efficiency and release studies, pharmacokinetic evaluation, and efficacy and safety testing in clinically relevant CRC models. This production-to-functionalization-to-application framework positions Frondoside A delivery as a focused example of marine-biopolymer innovation for biomedical use.