Natural Bioactive Compounds as Therapeutic Agents: Overcoming Delivery Barriers Through Nanotechnology-Based Formulation Strategies

Abstract

Natural bioactive compounds derived from plants, microorganisms, and marine organisms have attracted considerable pharmaceutical interest owing to their broad spectrum of biological activities, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antiviral, neuroprotective, and cardioprotective effects. Despite this promise, clinical translation of these molecules remains constrained by poor aqueous solubility, limited membrane permeability, chemical instability, extensive first-pass metabolism, and inadequate systemic bioavailability. Nanotechnology-based delivery systems address these limitations by improving dissolution, protecting labile molecules from degradation, enhancing absorption, and enabling controlled or site-specific release. This review synthesizes current evidence on the classification and mechanisms of action of natural bioactive compounds, the biopharmaceutical barriers restricting their clinical use, and the principal nanocarrier platforms including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, nanoemulsions, micelles, transferosomes, ethosomes, and biomimetic systems that have been used to improve their delivery, including their representative preparation methods and typical particle-size ranges. Disease-specific applications in oncology, cardiovascular disease, neurodegeneration, metabolic disorders, and infection are discussed alongside the growing roles of Quality by Design (QbD) frameworks and artificial intelligence (AI) in predictive formulation development and personalized nanomedicine. The review concludes with a discussion of the regulatory landscape and identifies the translational, manufacturing, and evidentiary challenges that must be addressed to move natural product nanomedicines from bench to bedside.