The growing interest in sustainable and biocompatible drug delivery platforms has stimulated research at the interface of natural bioactive compounds and biodegradable nanobiocomposite systems. Although plant-derived molecules such as flavonoids, alkaloids, terpenoids, and polyphenols exhibit diverse pharmacological activities, their clinical utility is often constrained by poor solubility, chemical instability, rapid metabolism, and non-specific biodistribution. Nanotechnology-enabled delivery systems have been explored to mitigate these limitations through enhanced solubilization, protection from degradation, and controlled release; however, most reported benefits remain confined to in-vitro and small-animal studies, with limited clinical validation. Biodegradable nanobiocomposites composed of biopolymers (e.g., chitosan, alginate, and plant-derived gums) and nanoscale reinforcements produced via green synthesis routes have shown favourable encapsulation efficiencies and stimulus-responsive behaviour at the preclinical level. Despite these advances, critical knowledge gaps persist regarding long-term safety, pharmacokinetics, degradation pathways, and reproducibility, particularly for eco-friendly systems derived from natural sources. Furthermore, green synthesis strategies—including plant-mediated, microbial, enzyme-assisted, and polymer-supported approaches—face challenges related to batch-to-batch variability, yield optimisation, and scale-up. This review critically evaluates the current state of biodegradable nanobiocomposites for natural bioactive delivery, highlighting unresolved translational barriers, regulatory considerations, and the need for robust in-vivo and clinical studies before therapeutic claims can be reliably substantiated.
Sahoo et al. (Tue,) studied this question.