Nanocarrier-Mediated Pharmacokinetic Optimization of Piperine: Expanding the Therapeutic Spectrum of a Multifaceted Bioactive Compound

Piperine, the principal bioactive alkaloid of Piper nigrum, has emerged as a potent phytoconstituent with a diverse pharmacological portfolio spanning anticancer, antiinflammatory, antimicrobial, anti-diabetic, and neuroprotective domains. Despite its therapeutic versatility, Piperine's clinical translation is significantly hindered by physicochemical constraints, including low aqueous solubility, poor oral bioavailability, and crystallization-induced instability. Central to overcoming these barriers is the advent of nanostructured drug delivery systems. Nanocarriers such as liposomes, solid lipid nanoparticles, polymeric micelles, and electrospun nanofibers not only enhance solubility and protect against degradation but also enable controlled, site-specific delivery. This review examines three core aspects driving the development of Piperine- based therapies: inherent molecular limitations, innovations in formulation techniques, and the potential for clinical translation. Detailed discussions encompass design strategies, synthesis techniques, and characterization protocols, supported by in-vitro/in-vivo efficacy studies. By critically synthesizing recent advances, the article highlights the transformative role of nano-enabled formulations in extending the therapeutic reach of phytoconstituent-based interventions, paving the way for future clinical integration.