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Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: an Overview

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Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: an Overview cancers Review Advances in Nanocarriers for Effective Delivery of Docetaxel in the Treatment of Lung Cancer: An Overview S. Aishah A. Razak 1, Amirah Mohd Gazzali 1,* , Faisalina Ahmad Fisol 1,2, Ibrahim M. Abdulbaqi 1 , Thaigarajan Parumasivam 1, Noratiqah Mohtar 1 and Habibah A. Wahab 1,* 1 School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia; [email protected] (S.A.A.R.); [email protected] (F.A.F.); [email protected] (I.M.A.); [email protected] (T.P.); [email protected] (N.M.) 2 Malaysian Institute of Pharmaceuticals and Nutraceuticals (IPharm), National Institute of Biotechnology Malaysia (NIBM), Ministry of Science, Technology and Innovation (MOSTI), Gelugor, Penang 11700, Malaysia * Correspondence: [email protected] (H.A.W.); [email protected] (A.M.G.) Simple Summary: As lung cancer has the highest incidence rate compared to any other type of cancer, there have been extensive research studies aiming at finding a better treatment for curing this disease. One of the many approaches is by improving the delivery of anticancer drugs towards cancer cells using advanced technologies. In this review, we focused on docetaxel as one of the most commonly used drugs for lung cancer treatment and discussed the properties of the drug and the application of nanotechnology in delivering this drug to improve its efficacy and specificity while reducing its side effects. Abstract: Docetaxel (DCX) is a highly effective chemotherapeutic drug used in the treatment of different types of cancer, including non-small cell lung cancer (NSCLC). The drug is known to have low oral bioavailability due to its low aqueous solubility, poor membrane permeability and Citation: A. Razak, S.A.; Mohd Gazzali, A.; Fisol, F.A.; susceptibility to hepatic first-pass metabolism. To mitigate these problems, DCX is administered via M. Abdulbaqi, I.; Parumasivam, T.; the intravenous route. Currently, DCX is commercially available as a single vial that contains polysor- Mohtar, N.; A. Wahab, H. Advances bate 80 and ethanol to solubilize the poorly soluble drug. However, this formulation causes short- in Nanocarriers for Effective Delivery and long-term side effects, including hypersensitivity, febrile neutropenia, fatigue, fluid retention, of Docetaxel in the Treatment of Lung and peripheral neuropathy. DCX is also a substrate to the drug efflux pump P-glycoprotein (P-gp) Cancer: An Overview. Cancers 2021, that would reduce its concentration within the vicinity of the cells and lead to the development of 13, 400. https://doi.org/10.3390/ drug resistance. Hence, the incorporation of DCX into various nanocarrier systems has garnered a cancers13030400 significant amount of attention in recent years to overcome these drawbacks. The surfaces of these drug-delivery systems indeed can be functionalized by modification with different ligands for smart Academic Editor: Samuel Mok targeting towards cancerous cells. This article provides an overview of the latest nanotechnological Received: 12 November 2020 approaches and the delivery systems that were developed for passive and active delivery of DCX via Accepted: 24 December 2020 Published: 22 January 2021 different routes of administration for the treatment of lung cancer. Publisher’s Note: MDPI stays neu- Keywords: docetaxel; nanoparticles; lung cancer; drug delivery; non-small cell lung cancer (NSCLC) tral with regard to jurisdictional clai- ms in published maps and institutio- nal affiliations. 1. Introduction Among all types of cancers, lung cancer is the most commonly diagnosed in both males and females globally and also the leading cause of cancer-related deaths [1]. Research Copyright: © 2021 by the authors. Li- censee MDPI, Basel, Switzerland. studies are continuously carried out to find a better solution in treating lung cancer as the This article is an open access article current treatment regimen often associated with nonspecific and nonselective cytotoxic distributed under the terms and con- chemotherapy or surgery. There are several classes of drugs that have been approved by ditions of the Creative Commons At- the United States Food and Drug Administration (US FDA) to treat lung cancer, and among tribution (CC BY) license (https:// the commonly used ones is the antineoplastic taxane: docetaxel (DCX). creativecommons.org/licenses/by/ Docetaxel, discovered by Pierre Potier in National Center for Scientific Research in 4.0/). France during the 1980s, belongs to the taxoid class of cytotoxic agents together with Cancers 2021, 13, 400. https://doi.org/10.3390/cancers13030400 https://www.mdpi.com/journal/cancers Cancers 2021, 13, x FOR PEER REVIEW 2 of 25 toxic chemotherapy or surgery. There are several classes of drugs that have been ap- proved by the United States Food and Drug Administration (US FDA) to treat lung cancer, Cancers 2021, 13, 400 and among the commonly used ones is the antineoplastic taxane: docetaxel (DCX). 2 of 25 Docetaxel, discovered by Pierre Potier in National Center for Scientific Research in France during the 1980s, belongs to the taxoid class of cytotoxic agents together with paclitaxel (PCX) [2]. In 1971, paclitaxel (taxol) was identified as the active compound of paclitaxel (PCX) [2]. In 1971, paclitaxel (taxol) was identified as the active compound of the the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. Due to the limited crude extract of the bark of the Pacific Yew tree Taxus brevifolia. Due to the limited supply supply of the drug from the natural product, there was a race to improve the production of the drug from the natural product, there was a race to improve the production or find a or find a new synthetic route of PCX. While working on the efficient partial synthesis of new synthetic route of PCX. While working on the efficient partial synthesis of PCX from its PCX from its congener, 10-deacetylbaccatin III [2], Portier discovered docetaxel. 10-deace- congener, 10-deacetylbaccatin III [2], Portier discovered docetaxel. 10-deacetylbaccatin III tylbaccatin III has also been reported to be isolated from other members of the Taxus fam- has also been reported to be isolated from other members of the Taxus family (e.g., T. baccata ily (e.g., T. baccata and T. brevifolia) trees [3]. DCX has a structure similar to paclitaxel ex- and T. brevifolia) trees [3]. DCX has a structure similar to paclitaxel except for its tert-Butyl cept for its tert-Butyl carbamate ester in the side chain of the phenylpropionate and the carbamate ester in the side chain of the phenylpropionate and the hydroxyl functional hydroxyl functional group on carbon-10 (Figure 1). The difference in their structures group on carbon-10 (Figure1). The difference in their structures makes DCX slightly more makessoluble DCX in water slightly than more PCX soluble [4]. in water than PCX [4]. Figure 1. Chemical structure of docetaxel (left) and paclitaxel (right). Figure 1. Chemical structure of docetaxel (left) and paclitaxel (right). DCX was first approved by the US FDA for the treatment of breast cancer in 1996. It was alsoDCX tested was first in the approved clinical by trials the for US use FDA the for in th treatmente treatment of non-smallof breast cancer cell lung in 1996. cancer It (NSCLC)was also tested by Aventis in the Pharmaceuticalclinical trials for Inc., use Paris,the in France,treatment (now of non-small Sanofi) as cell an intravenouslung cancer (NSCLC)formulation by TaxotereAventis® Pharmaceutical. Later, it was approved Inc., Pari fors, theFrance, treatment (now ofSanofi) NSCLC as inan patients intravenous with formulationlocally advanced Taxotere or metastatic®. Later, it NSCLCwas approved upon failure for the of tr platinumeatment of therapy NSCLC as in a patients single agent with locallyin 1999. advanced In 2002, or Taxotere metastatic® was NSCLC also approved upon failure for theof platinum treatment therapy of locally as a advanced single agent or inmetastatic 1999. In untreated2002, Taxotere NSCLC® was with also cisplatin. approved In additionfor the treatment to lungcancer, of locally its useadvanced has been or metastaticindicated foruntreated squamous NSCLC cell cancer with cisplatin. of the head In andaddition neck, to gastric lung adenocarcinoma,cancer, its use has breast been indicatedcancer and for prostate squamous cancer cell [5 cancer] due to of its the cytotoxic head and effect neck, on gastric microtubules adenocarcinoma, [6]. breast cancerThe and cytotoxic prostate effect cancer on [5] microtubules due to its cytotoxic originates effect from on the microtubules mechanism [6]. of DCX that in- hibitsThe cell cytotoxic proliferation effect by on inducing microtubules a sustained origin blockates atfrom the the metaphase-anaphase mechanism of DCX boundary that in- hibitsduring cell cell proliferation division, thus by disrupting inducing thea sustained microtubular block network at the metaphase-anaphase that is significant for bound- mitotic arycell divisionduring cell [7]. division, DCX also thus inhibits disrupting the depolymerisation the microtubular of the network microtubule that is back significant to tubulin for mitoticthat leads cell to division the failure [7]. ofDCX cell also division inhibits and the eventually, depolymerisation cell death of [ 8the]. Sincemicrotubule DCX affects back tocell tubulin division, that the leads drug to the is not failure only of cytotoxic cell division to cancer and eventually, cells but also cell cytotoxicdeath [8]. toSince the DCX hair affectsfollicles, cell bone division, marrow
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