From Citrus to Clinic: Limonene’s Journey Through Preclinical Research, Clinical Trials, and Formulation Innovations

Sanshita,1 Naina Devi,1 Bidisha Bhattacharya,1 Ankita Sharma,1 Inderbir Singh,1 Pradeep Kumar,2,3 Kampanart Huanbutta,4 Tanikan Sangnim5 1Chitkara College of Pharmacy, Chitkara University, Patiala, Punjab, India; 2Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 3Department of Pharmaceutical Sciences, Maharshi Dayanand University, Haryana, India; 4Department of Manufacturing Pharmacy, College of Pharmacy, Rangsit University, Pathum Thani, Thailand; 5Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi, ThailandCorrespondence: Tanikan Sangnim, Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Burapha University, 169, Seansook, Muang, Chonburi, 20131, Thailand, Email [email protected]: Limonene is a naturally occurring monoterpene found in oranges, lemons, grapefruit, fennel, and caraway, and is a part of essential oils of different plants. It has caught the eye of the research community owing to its innumerable health benefits. It exhibits significant antioxidant, anti-inflammatory, wound-healing, antidiabetic, anticancer, and immunomodulatory activities. These activities of limonene render it an indispensable compound in both traditional and modern medicine. This article presents a thorough compilation of the various therapeutic activities of limonene and the mechanisms underlying them. Furthermore, it delves into an in-depth discussion of the role of nanoformulations and novel drug delivery systems in ensuring the targeted delivery of limonene. To substantiate the safety and efficacy of limonene, a large number of preclinical and clinical studies have been conducted by researchers have also been discussed in detail in this review. Limonene is an unparalleled terpenoid with numerous therapeutic benefits. Incorporating it into sophisticated drug delivery systems and medical devices, together with personalised medicine strategies, signifies notable progress in its therapeutic use. Technologies, such as 3D printing, nanoformulations, and microneedles, can improve the ability of limonene to be absorbed by the body and targeted to specific areas. Keywords: limonene, antioxidant, anti-inflammatory, antidiabetic, anticancer, preclinical studies, clinical studies, formulations, nanoparticles