About 42 % of drugs with market acceptance and 92 % of drugs in the discovery pipeline are imperfectly aqueous soluble with insufficient intestinal absorption and will suffer from low oral bioavailability. Alkaloids are a group of phytonutrients that has been examined broadly due to their various health-related benefits. However, most of the alkaloids are considered as compounds with less aqueous solubility which limits their human usefulness. Piperine (PIP) is a family of nitrogenous aggregates that are extracted from the black pepper (Piper nigrum). It holds various therapeutic effects such as antioxidant, anti-inflammatory, neuroprotective, anti-cancer, anti-microbial, hepatoprotective, anti-depressant, anti-obesity, cardioprotective, P-gp inhibitor, anti-aging, and permeation enhancer. Although both the preclinical and clinical studies confirmed the advantages of PIP, its clinical usefulness is restricted due to its low water solubility and poor bioabsorption. To overcome these limitations nanoformulation is a widely employed approach. Multiple reviews have confirmed PIP health-related benefits, still, there is a lack of comprehensive review focused on its chemistry, pharmacological effects, nanoformulation, toxicity, advantages and challenges of PIP nanosystem, and marketed herbal formulations. However, this study aims to deliver a review of several nanoformulation development and nano-technology-based approaches employed to upregulate the solubility, bioabsorption, and therapeutic efficiency of PIP. We have also reviewed information related to the toxicity of PIP and its formulations.
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