Generic placeholder image

Drug Delivery Letters


ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Review Article

Erlotinib Hydrochloride Novel Drug Delivery Systems: A Mini Review Unravelling the Role of Micro- and Nanocarriers

Author(s): Chaitali Taiwade, Aditi Fulfager, Hardik Bhargave, Govind Soni and Khushwant Yadav*

Volume 11, Issue 4, 2021

Published on: 26 August, 2021

Page: [295 - 306] Pages: 12

DOI: 10.2174/2210303111666210827094543

Price: $65


Erlotinib is a tyrosine kinase inhibitor and it can treat tumors, such as pancreatic and locally advanced lung cancer or metastatic cancer. The traditional formulation of erlotinib currently available is an oral delivery type that presents serious side effects such as hepatotoxicity, skin rashes, gastrointestinal disturbance, renal dysfunction, drug resistance and hematological symptoms. Besides this, other disadvantages of erlotinib provided mostly by oral administration are the comprehensive metabolism, low bioavailability, poor solubility and off-target impact. Overcoming such unfavorable attributes of the medication, innovative medication delivery mechanisms like nanocapsules, liposomes, microspheres, microparticles solid lipid nanoparticles, nanosponge, and nanoparticles have been studied that have really shown their lead over traditional formulations. This article summarizes the novel erlotinib drug delivery systems to boost its clinical efficacy and reduce systemic toxicity. Novel formulations of erlotinib will offer positive outcomes in cancer therapy and will play an important part in improving the drug's therapeutic potential.

Keywords: Erlotinib, oral delivery, adverse effects, nanoparticles, liposomes, microparticles, co-delivery systems, targeting.

Graphical Abstract
Korgaonkar, N.; Yadav, K.S. Understanding the biology and advent of physics of cancer with perspicacity in current treatment therapy. Life Sci., 2019, 239, 117060.
[] [PMID: 31733317]
Cui, Y.; Dong, H.; Cai, X.; Wang, D.; Li, Y. Mesoporous silica nanoparticles capped with disulfide-linked PEG gatekeepers for glutathione-mediated controlled release. ACS Appl. Mater. Interfaces, 2012, 4(6), 3177-3183.
[] [PMID: 22646097]
Minuti, G.; D’Incecco, A.; Cappuzzo, F. Targeted therapy for NSCLC with driver mutations. Expert Opin. Biol. Ther., 2013, 13(10), 1401-1412.
[] [PMID: 23930754]
Pao, W.; Girard, N. New driver mutations in non-small-cell lung cancer. Lancet Oncol., 2011, 12(2), 175-180.
[] [PMID: 21277552]
Keedy, V.L.; Temin, S.; Somerfield, M.R.; Beasley, M.B.; Johnson, D.H.; McShane, L.M.; Milton, D.T.; Strawn, J.R.; Wakelee, H.A.; Giaccone, G. American Society of Clinical Oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J. Clin. Oncol., 2011, 29(15), 2121-2127.
[] [PMID: 21482992]
Rosell, R.; Carcereny, E.; Gervais, R.; Vergnenegre, A.; Massuti, B.; Felip, E.; Palmero, R.; Garcia-Gomez, R.; Pallares, C.; Sanchez, J.M.; Porta, R.; Cobo, M.; Garrido, P.; Longo, F.; Moran, T.; Insa, A.; De Marinis, F.; Corre, R.; Bover, I.; Illiano, A.; Dansin, E.; de Castro, J.; Milella, M.; Reguart, N.; Altavilla, G.; Jimenez, U.; Provencio, M.; Moreno, M.A.; Terrasa, J.; Muñoz-Langa, J.; Valdivia, J.; Isla, D.; Domine, M.; Molinier, O.; Mazieres, J.; Baize, N.; Garcia-Campelo, R.; Robinet, G.; Rodriguez-Abreu, D.; Lopez-Vivanco, G.; Gebbia, V.; Ferrera-Delgado, L.; Bombaron, P.; Bernabe, R.; Bearz, A.; Artal, A.; Cortesi, E.; Rolfo, C.; Sanchez-Ronco, M.; Drozdowskyj, A.; Queralt, C.; de Aguirre, I.; Ramirez, J.L.; Sanchez, J.J.; Molina, M.A.; Taron, M.; Paz-Ares, L. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial. Lancet Oncol., 2012, 13(3), 239-246.
[] [PMID: 22285168]
Darandale, S.S.; Vavia, P.R. Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. J. Incl. Phenom. Macrocycl. Chem., 2013, 75, 315-322.
Becker, A.; van Wijk, A.; Smit, E.F.; Postmus, P.E. Side-effects of long-term administration of erlotinib in patients with non-small cell lung cancer. J. Thorac. Oncol., 2010, 5(9), 1477-1480.
[] [PMID: 20736807]
Taetz, S.; Bochot, A.; Surace, C.; Arpicco, S.; Renoir, J.M.; Schaefer, U.F.; Marsaud, V.; Kerdine-Roemer, S.; Lehr, C.M.; Fattal, E. Hyaluronic acid-modified DOTAP/DOPE liposomes for the targeted delivery of anti-telomerase siRNA to CD44-expressing lung cancer cells. Oligonucleotides, 2009, 19(2), 103-116.
[] [PMID: 19374532]
Gridelli, C.; Bareschino, M.A.; Schettino, C.; Rossi, A.; Maione, P.; Ciardiello, F. Erlotinib in non-small cell lung cancer treatment: current status and future development. Oncologist, 2007, 12(7), 840-849.
[] [PMID: 17673615]
Soni, G.; Yadav, K.S. Applications of nanoparticles in treatment and diagnosis of leukemia. Mater. Sci. Eng. C, 2015, 47, 156-164.
[] [PMID: 25492184]
Aveling, E.; Zhou, J.; Lim, Y.F.; Mozafari, M.R. Targeting lipidic nanocarriers: Current strategies and problems. Pharmakeftiki, 2006, 19(IV), 101-109.
Maherani, B.; Arab-Tehrany, E.; R Mozafari, M.; Gaiani, C.; Linder, M. Liposomes: A review of manufacturing techniques and targeting strategies. Curr. Nanosci., 2011, 7(3), 436-452.
Bethune, G.; Bethune, D.; Ridgway, N.; Xu, Z. Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update. J. Thorac. Dis., 2010, 2(1), 48-51.
[PMID: 22263017]
Smith, N.F.; Baker, S.D.; Gonzalez, F.J.; Harris, J.W.; Figg, W.D.; Sparreboom, A. Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100. Br. J. Cancer, 2008, 98(10), 1630-1632.
[] [PMID: 18475295]
Belpaire, F.M.; Bogaert, M.G. The fate of xenobiotics in living organisms. In: The practice of medicinal chemistry, 2nd ed; Wermuth, C.G., Ed.; Academic Press, An imprint of Elsevier Science: Amsterdam, 2003; pp. 501-515.
Pajares, B.; Torres, E.; Trigo, J.M.; Sáez, M.I.; Ribelles, N.; Jiménez, B.; Alba, E. Tyrosine kinase inhibitors and drug interactions: A review with practical recommendations. Clin. Transl. Oncol., 2012, 14(2), 94-101.
[] [PMID: 22301397]
Marslin, G.; Sheeba, C.J.; Kalaichelvan, V.K.; Manavalan, R.; Reddy, P.N.; Franklin, G. Poly(D,L-lactic-co-glycolic acid) nanoencapsulation reduces Erlotinib-induced subacute toxicity in rat. J. Biomed. Nanotechnol., 2009, 5(5), 464-471.
[] [PMID: 20201419]
Hatziagapiou, K.; Bethanis, K.; Lambrou, G.I.; Yannakopoulou, K.; Karpusas, M.; Braoudaki, M.; Christoforides, E.; Tsorteki, F.; Milionis, V.; Kavantzas, N.; Tzortzatou-Stathopoulou, F. Enhanced gefitinib cytotoxicity in the presence of cyclodextrins: In-vitro and biophysical studies towards potential therapeutic interventions for cancer. J. Biomed. Nanotechnol., 2017, 13(5), 522-533.
Matsumura, Y.; Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res., 1986, 46(12 Pt 1), 6387-6392.
[PMID: 2946403]
Da Silva, C.G.; Peters, G.J.; Ossendorp, F.; Cruz, L.J. The potential of multi-compound nanoparticles to bypass drug resistance in cancer. Cancer Chemother. Pharmacol., 2017, 80(5), 881-894.
[] [PMID: 28887666]
Mozafari, M.R. Nanoliposomes: Preparation and analysis, in Liposomes - Methods and ProtocolsPharm. Nanocarriers; Weissig, V., Ed.; Humana Press: New York, NY, 2010, pp. 41-62.
Mozafari, M.R.; Khosravi-Darani, K. An overview of liposome-derived nanocarrier technologies. Nanomaterials and Nanosystems for Biomedical Applications; Dordrecht, M.M.R., Ed.; Springer Netherlands, 2007, pp. 113-123.
Elmeshad, A.N.; Mortazavi, S.M.; Mozafari, M.R. Formulation and characterization of nanoliposomal 5-fluorouracil for cancer nanotherapy. J. Liposome Res., 2014, 24(1), 1-9.
[] [PMID: 23834067]
Dhoble, S.; Patravale, V. Development of anti-angiogenic erlotinib liposomal formulation for pulmonary hypertension: A QbD approach. Drug Deliv. Transl. Res., 2019, 9(5), 980-996.
[] [PMID: 31001718]
Zhou, X.; Tao, H.; Shi, K.H. Development of a nanoliposomal formulation of erlotinib for lung cancer and in vitro/in vivo antitumoral evaluation. Drug Des. Devel. Ther., 2017, 12, 1-8.
[] [PMID: 29296076]
Xu, H.; He, C.; Liu, Y.; Jiang, J.; Ma, T. Novel therapeutic modalities and drug delivery - erlotinib liposomes modified with galactosylated lipid: in vitro and in vivo investigations. Artif. Cells Nanomed. Biotechnol., 2018, 46(8), 1902-1907.
[PMID: 29081246]
Upadhya, A.; Yadav, K.S.; Misra, A. Targeted drug therapy in non-small cell lung cancer: Clinical significance and possible solutions-Part I. Expert Opin. Drug Deliv., 2021, 18(1), 73-102.
[] [PMID: 32954834]
Abedi Gaballu, F.; Abbaspour-Ravasjani, S.; Mansoori, B.; Yekta, R.; Hamishehkar, H.; Mohammadi, A.; Dehghan, G.; Shokouhi, B.; Ghahremani Dehbokri, S.; Baradaran, B. Comparative of in-vitro evaluation between erlotinib loaded nanostructured lipid carriers and liposomes against A549 lung cancer cell line. Iran. J. Pharm. Res., 2019, 18(3), 1168-1179.
[PMID: 32641930]
Li, F.; Mei, H.; Xie, X.; Zhang, H.; Liu, J.; Lv, T.; Nie, H.; Gao, Y.; Jia, L. Aptamer-conjugated chitosan-anchored liposomal complexes for targeted delivery of erlotinib to EGFR-mutated lung cancer cells. AAPS J., 2017, 19(3), 814-826.
[] [PMID: 28233244]
Deshpande, P.P.; Biswas, S.; Torchilin, V.P. Current trends in the use of liposomes for tumor targeting. Nanomedicine (Lond.), 2013, 8(9), 1509-1528.
[] [PMID: 23914966]
Lee, Y.S.; Johnson, P.J.; Robbins, P.T.; Bridson, R.H. Production of nanoparticles-in-microparticles by a double emulsion method: A comprehensive study. Eur. J. Pharm. Biopharm., 2013, 83(2), 168-173.
[] [PMID: 23153669]
Pandey, P.; Dua, K.; Dureja, H. Erlotinib loaded chitosan nanoparticles: Formulation, physicochemical characterization and cytotoxic potential. Int. J. Biol. Macromol., 2019, 139, 1304-1316.
[] [PMID: 31404602]
Noorani, M.; Azarpira, N.; Karimian, K.; Heli, H. Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines. Int. J. Pharm., 2017, 531(1), 299-305.
[] [PMID: 28847671]
He, Y.; Su, Z.; Xue, L.; Xu, H.; Zhang, C. Co-delivery of erlotinib and doxorubicin by pH-sensitive charge conversion nanocarrier for synergistic therapy. J. Control. Release, 2016, 229, 80-92.
[] [PMID: 26945977]
Vaidya, B.; Parvathaneni, V.; Kulkarni, N.S.; Shukla, S.K.; Damon, J.K.; Sarode, A.; Kanabar, D.; Garcia, J.V.; Mitragotri, S.; Muth, A.; Gupta, V. Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer. Biol. Macromol., 2019, 122, 338-347.
[] [PMID: 30401652]
Fathi, M.; Zangabad, P.S.; Aghanejad, A.; Barar, J.; Erfan-Niya, H.; Omidi, Y. Folate-conjugated thermosensitive O-maleoyl modified chitosan micellar nanoparticles for targeted delivery of erlotinib. Carbohydr. Polym., 2017, 172, 130-141.
[] [PMID: 28606519]
Barghi, L.; Asgari, D.; Barar, J.; Nakhlband, A.; Valizadeh, H. Synthesis, characterization and in vitro anti-tumoral evaluation of Erlotinib-PCEC nanoparticles. Asian Pac. J. Cancer Prev., 2014, 15(23), 10281-10287.
[] [PMID: 25556462]
Trotta, F.; Cavalli, R.; Tumiatti, W.; Zerbinati, O.; Rogero, C.; Vallero, R. ltrasound-assisted synthesis of Cyclodextrin-based nanosponges. EP 1 786 841 B1, 2007.
Momin, M.M.; Zaheer, Z.; Zainuddin, R.; Sangshetti, J.N. Extended release delivery of erlotinib glutathione nanosponge for targeting lung cancer. Artif. Cells Nanomed. Biotechnol., 2018, 46(5), 1064-1075.
[] [PMID: 28758795]
Dora, C.P.; Trotta, F.; Kushwah, V.; Devasari, N.; Singh, C.; Suresh, S.; Jain, S. Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability. Carbohydr. Polym., 2016, 137, 339-349.
[] [PMID: 26686138]
Müller, R.H.; Mäder, K.; Gohla, S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur. J. Pharm. Biopharm., 2000, 50(1), 161-177.
[] [PMID: 10840199]
Nassimi, M.; Schleh, C.; Lauenstein, H.D.; Hussein, R.; Hoymann, H.G.; Koch, W.; Pohlmann, G.; Krug, N.; Sewald, K.; Rittinghausen, S.; Braun, A.; Müller-Goymann, C. A toxicological evaluation of inhaled solid lipid nanoparticles used as a potential drug delivery system for the lung. Eur. J. Pharm. Biopharm., 2010, 75(2), 107-116.
[] [PMID: 20206256]
Bakhtiary, Z.; Barar, J.; Aghanejad, A.; Saei, A.A.; Nemati, E.; Ezzati Nazhad Dolatabadi, J.; Omidi, Y. Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer. Drug Dev. Ind. Pharm., 2017, 43(8), 1244-1253.
[] [PMID: 28323493]
Mandal, B.; Bhattacharjee, H.; Mittal, N.; Sah, H.; Balabathula, P.; Thoma, L.A.; Wood, G.C. Core-shell-type lipid-polymer hybrid nanoparticles as a drug delivery platform. Nanomedicine, 2013, 9(4), 474-491.
[] [PMID: 23261500]
Kim, J.; Ramasamy, T.; Choi, J.Y.; Kim, S.T.; Youn, Y.S.; Choi, H.G.; Yong, C.S.; Kim, J.O. PEGylated polypeptide lipid nanocapsules to enhance the anticancer efficacy of erlotinib in non-small cell lung cancer. Colloids Surf. B Biointerfaces, 2017, 150, 393-401.
[] [PMID: 27825759]
Gupta, B.; Poudel, B.K.; Regmi, S.; Pathak, S.; Ruttala, H.B.; Gautam, M.; An, G.J.; Jeong, J.H.; Choi, H.G.; Yong, C.S.; Kim, J.O. Paclitaxel and Erlotinib-co-loaded Solid Lipid Core Nanocapsules: Assessment of Physicochemical Characteristics and Cytotoxicity in Non-small Cell Lung Cancer. Pharm Res., 2018, 35(5), 96.
Varde, N.K.; Pack, D.W. Microspheres for controlled release drug delivery. Expert Opin. Biol. Ther., 2004, 4(1), 35-51.
[] [PMID: 14680467]
Cheng, F.; Peng, X.; Meng, G.; Pu, Y.; Luo, K.; He, B. Poly(ester-thioether) microspheres co-loaded with erlotinib and α-tocopheryl succinate for combinational therapy of non-small cell lung cancer. J. Mater. Chem. B Mater. Biol. Med., 2020, 8(8), 1728-1738.
[] [PMID: 32022097]
Soni, G.; Yadav, K.S.; Gupta, M.K. QbD based approach for formulation development of spray dried microparticles of erlotinib hydrochloride for sustained release. J. Drug Deliv. Sci. Technol. J., Drug Deliv. Sci. Tec., 2020, 57, 101684.
Soni, G.; Yadav, K.S.; Gupta, M.K. Design of Experiments (DoE) Approach to Optimize the Sustained Release Microparticles of Gefitinib. Curr. Drug Deliv., 2019, 16(4), 364-374.
[] [PMID: 30588883]
Yadav, K.S.; Sawant, K.K. Formulation optimization of etoposide loaded PLGA nanoparticles by double factorial design and their evaluation. Curr. Drug Deliv., 2010, 7(1), 51-64.
[] [PMID: 20044908]
Pethe, A.M.; Yadav, K.S. Polymers, responsiveness and cancer therapy. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 395-405.
[] [PMID: 30688110]
Yadav, K.S.; Saxena, R.; Soni, G. Nanogels as targeted drug delivery vehicles. Nanogels Biomed. Appl., 2017, 30, 143.
Fathi, M.; Sahandi Zangabad, P.; Barar, J.; Aghanejad, A.; Erfan-Niya, H.; Omidi, Y. Thermo-sensitive chitosan copolymer-gold hybrid nanoparticles as a nanocarrier for delivery of erlotinib. Int. J. Biol. Macromol., 2018, 106, 266-276.
[] [PMID: 28802850]
Mandal, B.; Mittal, N.K.; Balabathula, P.; Thoma, L.A.; Wood, G.C. Development and in vitro evaluation of core-shell type lipid-polymer hybrid nanoparticles for the delivery of erlotinib in non-small cell lung cancer. Eur. J. Pharm. Sci., 2016, 81, 162-171.
[] [PMID: 26517962]
Fulfager, A.; Yadav, K.S. Understanding the implications of co-delivering therapeutic agents in a nanocarrier to combat multidrug resistance (MDR) in breast cancer. J. Drug Deliv. Sci. Tec., 2021, 62, 102405.
Teo, P.Y.; Cheng, W.; Hedrick, J.L.; Yang, Y.Y. Co-delivery of drugs and plasmid DNA for cancer therapy. Adv. Drug Deliv. Rev., 2016, 98, 41-63.
[] [PMID: 26529199]
Zhou, Z.; Kennell, C.; Jafari, M.; Lee, J.Y.; Ruiz-Torres, S.J.; Waltz, S.E.; Lee, J.H. Sequential delivery of erlotinib and doxorubicin for enhanced triple negative Breast cancer treatment using polymeric nanoparticle. Int. J. Pharm., 2017, 530(1-2), 300-307.
[] [PMID: 28778627]
Lakkadwala, S.; Singh, J. Co-delivery of doxorubicin and erlotinib through liposomal nanoparticles for glioblastoma tumor regression using an in vitro brain tumor model. Colloids Surf. B Biointerfaces, 2019, 173, 27-35.
[] [PMID: 30261346]
Pang, J.; Xing, H.; Sun, Y.; Feng, S.; Wang, S. Non-small cell lung cancer combination therapy: Hyaluronic acid modified, epidermal growth factor receptor targeted, pH sensitive lipid-polymer hybrid nanoparticles for the delivery of erlotinib plus bevacizumab. Biomed. Pharmacother., 2020, 125, 109861.
[] [PMID: 32070872]
Liu, J.; Zheng, J.; Nie, H.; Chen, H.; Li, B.; Jia, L. Co-delivery of erlotinib and doxorubicin by MoS2 nanosheets for synergetic photothermal chemotherapy of cancer. Chem. Eng. J., 2020, 381, 122541.
Chen, D.; Zhang, F.; Wang, J.; He, H.; Duan, S.; Zhu, R.; Chen, C.; Yin, L.; Chen, Y. Biodegradable nanoparticles mediated co-delivery of erlotinib (ELTN) and fedratinib (FDTN) toward the treatment of eltn-resistant non-small cell lung cancer (NSCLC) via suppression of the JAK2/STAT3 signaling pathway. Front. Pharmacol., 2018, 9, 1214.
[] [PMID: 30483119]
Yin, N.; Yu, H.; Zhang, X.; Lv, X. Enhancement of pancreatic cancer therapy efficacy by type-1 matrix metalloproteinase-functionalized nanoparticles for the selective delivery of gemcitabine and erlotinib. Drug Des. Devel. Ther., 2020, 14, 4465-4475.
[] [PMID: 33122890]
Shen, Y.; Li, W. HA/HSA co-modified erlotinib-albumin nanoparticles for lung cancer treatment. Drug Des. Devel. Ther., 2018, 12, 2285-2292.
[] [PMID: 30087553]
Yadav, K.S.; Mishra, D.K.; Deshpande, A.; Pethe, A.M. Levels of drug targeting. Basic Fundamentals Drug Del., 2019, 269-305.
Yadav, K.S.; Upadhya, A.; Misra, A. Targeted drug therapy in nonsmall cell lung cancer: clinical significance and possible solutions-part II (role of nanocarriers). Expert Opin. Drug Deliv., 2021, 18(1), 103-118.
[] [PMID: 33017541]
Yadav, K.S.; Prabhakar, B. Nanogels in Medicine.Handbook of Materials for Nanomedicine: Polymeric Nanomaterials; , 2020, p. 445.
Soni, G.; Yadav, K.S. Communication of drug loaded nanogels with cancer cell receptors for targeted delivery. Modeling, methodologies and tools for molecular and nano-scale communications, 2017, 503-515.
Chaudhary, S.; Singh, A.; Kumar, P.; Kaushik, M. Strategic targeting of non-small-cell lung cancer utilizing genetic material-based delivery platforms of nanotechnology. J. Biochem. Mol. Toxicol., 2021, 35(7), e22784.
[] [PMID: 33826765]
Li, F.; Mei, H.; Gao, Y.; Xie, X.; Nie, H.; Li, T.; Zhang, H.; Jia, L. Co-delivery of oxygen and erlotinib by aptamer-modified liposomal complexes to reverse hypoxia-induced drug resistance in lung cancer. Biomaterials, 2017, 145, 56-71.
[] [PMID: 28843733]

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy