Citation: Nair, A.B.; Gorain, B.; Pandey, M.; Jacob, S.; Shinu, P.; Aldhubiab, B.; Almuqbil, R.M.; Elsewedy, H.S.; Morsy, M.A. Tocotrienol in the Treatment of Topical Wounds: Recent Updates. Pharmaceutics 2022, 14, 2479. https://doi.org/10.3390/ pharmaceutics14112479 Academic Editor: Rosa Direito Received: 17 October 2022 Accepted: 14 November 2022 Published: 16 November 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Review Tocotrienol in the Treatment of Topical Wounds: Recent Updates Anroop B. Nair 1, * , Bapi Gorain 2, *, Manisha Pandey 3 , Shery Jacob 4 , Pottathil Shinu 5 , Bandar Aldhubiab 1 , Rashed M. Almuqbil 1 , Heba S. Elsewedy 1,6 and Mohamed A. Morsy 1,7 1 Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia 2 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, India 3 Department of Pharmaceutical Sciences, Central University of Haryana, SSH 17, Jant, Mahendergarh 123031, India 4 Department of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab Emirates 5 Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia 6 Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, Dariyah, Riyadh 13713, Saudi Arabia 7 Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt * Correspondence: anair@kfu.edu.sa (A.B.N.); bapi.gn@gmail.com (B.G.); Tel.: +966-536219868 (A.B.N.); +91-9088585676 (B.G.) Abstract: Healing wounds is an important attempt to keep the internal higher organs safe. Compli- cations in topical wound healing may lead to the formation of scars, which can affect the patient’s quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made to- cotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds. Keywords: tocotrienols; topical wound; nanotechnology; challenges; growth factor; wound closure; angiogenesis 1. Introduction Emerging trends regarding disease-specific molecular alteration at the disease site have focused on agents for treatments. Topical wound treatment processes to combat diseases have shown gradual improvement over the years. The concept of Galen, the Greek physician, on wound healing environments by requiring a moist condition has been widely implemented during 120–201 AD [1–3]. Outcomes of further research on wound treatment brought an- other consequence of epithelialization in an occluded environment, where the time to heal the wound is shorter when the wound healing microenvironment along with the essential components was maintained, compared to the wounds left open and exposed to the environ- ment [4,5]. Numerous research in recent years aims to bring novel agents in a new delivery tool to meet the requirements of ideal dressing [6]. Since the ancient period, exploring nature Pharmaceutics 2022, 14, 2479. https://doi.org/10.3390/pharmaceutics14112479 https://www.mdpi.com/journal/pharmaceutics