Inhaled Micro/Nanoparticulate Anticancer Drug Formulations: An Emerging Targeted Drug Delivery Strategy for Lung Cancers

Page: [162 - 178] Pages: 17

  • * (Excluding Mailing and Handling)

Abstract

Local delivery of drug to the target organ via inhalation offers enormous benefits in the management of many diseases. Lung cancer is the most common of all cancers and it is the leading cause of death worldwide. Currently available treatment systems (intravenous or oral drug delivery) are not efficient in accumulating the delivered drug into the target tumor cells and are usually associated with various systemic and dose-related adverse effects. The pulmonary drug delivery technology would enable preferential accumulation of drug within the cancer cell and thus be superior to intravenous and oral delivery in reducing cancer cell proliferation and minimising the systemic adverse effects. Site-specific drug delivery via inhalation for the treatment of lung cancer is both feasible and efficient. The inhaled drug delivery system is non-invasive, produces high bioavailability at a low dose and avoids first pass metabolism of the delivered drug. Various anticancer drugs including chemotherapeutics, proteins and genes have been investigated for inhalation in lung cancers with significant outcomes. Pulmonary delivery of drugs from dry powder inhaler (DPI) formulation is stable and has high patient compliance. Herein, we report the potential of pulmonary drug delivery from dry powder inhaler (DPI) formulations inhibiting lung cancer cell proliferation at very low dose with reduced unwanted adverse effects.

Keywords: Anticancer drugs, chemotherapeutic agents, dry powder inhaler formulations, inhalation, lung cancer, pulmonary drug delivery.

Graphical Abstract

[1]
Cozza G, Pinna LA, Moro S. Protein kinase CK2 inhibitors: a patent review. Expert Opin Ther Pat 2012; 22(9): 1081-97.
[2]
Cozza G, Pinna LA, Moro S. Kinase CK2 inhibition: an update. Curr Med Chem 2013; 20(5): 671-93.
[3]
Lindqvist A, Rodriguez-Bravo V, Medema RH. The decision to enter mitosis: feedback and redundancy in the mitotic entry network. J Cell Biol 2009; 185(2): 193-202.
[4]
Matsuoka S, Ballif BA, Smogorzewska A, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007; 316(5828): 1160-6.
[5]
Molina Julian R, Yang P, Cassivi Stephen D, Schild Steven E, Adjei Alex A. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc 2008; 83(5): 584-94.
[6]
Riessk J. Shifting paradigms in non-small cell lung cancer: an evolving therapeutic landscape. Am J Manag Care 2013; 19(19)(Suppl.): s390-7.
[7]
Rossi A, Tay R, Chiramel J, Prelaj A, Califano R. Current and future therapeutic approaches for the treatment of small cell lung cancer. Expert Rev Anticancer Ther 2018; 18(5): 473-86.
[8]
Goffin J, Lacchetti C, Ellis Peter M, Ung Yee C, Evans William K. First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review. J Thorac Oncol 2010; 5(2): 260-74.
[9]
Kuzmov A, Minko T. Nanotechnology approaches for inhalation treatment of lung diseases. J Control Release 2015; 219: 500-18.
[10]
Guastalla JP III, Dieras V. The taxanes: toxicity and quality of life considerations in advanced ovarian cancer. Br J Cancer 2003; 89(Suppl. 3): S16-22.
[11]
Lee H-Y, Mohammed Kamal A, Nasreen N. Nanoparticle-based targeted gene therapy for lung cancer. Am J Cancer Res 2016; 6(5): 1118-34.
[12]
Jiang J, Liu Y, Wu C, et al. Development of drug-loaded chitosan hollow nanoparticles for delivery of paclitaxel to human lung cancer A549 cells. Drug Dev Ind Pharm 2017; 43(8): 1304-13.
[13]
Zarogoulidis P, Chatzaki E, Porpodis K, et al. Inhaled chemotherapy in lung cancer: future concept of nanomedicine. Int J Nanomedicine 2012; 7: 1551-72.
[14]
Meenach SA, Anderson KW, Hilt JZ, McGarry RC, Mansour HM. High-performing dry powder inhalers of paclitaxel DPPC/DPPG lung surfactant-mimic multifunctional particles in lung cancer: physicochemical characterization, in vitro aerosol dispersion, and cellular studies. AAPS PharmSciTech 2014; 15(6): 1574-87.
[15]
Gomes dos Reis L, Svolos M, Hartwig B, Windhab N, Young PM, Traini D. Inhaled gene delivery: a formulation and delivery approach. Expert Opin Drug Deliv 2017; 14(3): 319-30.
[16]
Blumberg RS, Lencer WI, Simister NE, Bitonti AJ. Aerosol delivery of antibodies or neonatal Fc receptor binding proteintherapeutic agent conjugates to lung central airway for treatment of lung or autoimmune diseases. 2003-435608, 2003235536, 20030509.
[17]
Karra N, Nassar T, Laenger F, Benita S, Borlak J. Safety and proof-of-concept efficacy of inhaled drug loaded nano- and immunonanoparticles in a c-Raf transgenic lung cancer model. Curr Cancer Drug Targets 2013; 13(1): 11-29.
[18]
Islam N, Gladki E. Dry powder inhalers (DPIs)-A review of device reliability and innovation. Int J Pharm 2008; 360(1-2): 1-11.
[19]
Patton JS, Fishburn CS, Weers JG. The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc 2004; 1(4): 338-44.
[20]
Islam N, Rahman S. Pulmonary drug delivery: Implication for new strategy for pharmacotherapy for neurodegenerative disorders. Drug Discov Ther 2008; 2(5): 264-76.
[21]
Yapa SWS, Li J, Patel K, et al. Pulmonary and systemic pharmacokinetics of inhaled and intravenous colistin methanesulfonate in cystic fibrosis patients: targeting advantage of inhalational administration. Antimicrob. Agents Chemother., 2014, 58(5), 2570-2579, 2511 pp.
[22]
Borghardt JM, Weber B, Staab A, Kunz C, Formella S, Kloft C. Investigating pulmonary and systemic pharmacokinetics of inhaled olodaterol in healthy volunteers using a population pharmacokinetic approach. Br J Clin Pharmacol 2016; 81(3): 538-52.
[23]
Duret C, Merlos R, Wauthoz N, Sebti T, Vanderbist F, Amighi K. Pharmacokinetic evaluation in mice of amorphous itraconazole-based dry powder formulations for inhalation with high bioavailability and extended lung retention. Eur J Pharm Biopharm 2014; 86(1): 46-54.
[24]
Hobbs SK, Monsky WL, Yuan F, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA 1998; 95(8): 4607-12.
[25]
Davis ME, Chen Z, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 2008; 7(9): 771-82.
[26]
Anabousi S, Bakowsky U, Schneider M, Huwer H, Lehr C-M, Ehrhardt C. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for inhalation therapy of lung cancer. Eur J Pharm Sci 2006; 29(5): 367-74.
[27]
Gaspar MM, Radomska A, Gobbo OL, Bakowsky U, Radomski MW, Ehrhardt C. Targeted delivery of transferrin-conjugated liposomes to an orthotopic model of lung cancer in nude rats. J Aerosol Med Pulm Drug Deliv 2012; 25(6): 310-8.
[28]
Shao Z, Tan B, Guan S, et al. Targeted lung cancer therapy: preparation and optimization of transferrin-decorated nanostructured lipid carriers as novel nanomedicine for co-delivery of anticancer drugs and DNA. Int J Nanomedicine 2015; 10: 1223-33.
[29]
Tagami T, Ando Y, Ozeki T. Fabrication of liposomal doxorubicin exhibiting ultrasensitivity against phospholipase A2 for efficient pulmonary drug delivery to lung cancers. Int J Pharm 2017; 517(1-2): 35-41.
[30]
Tseng C-L, Su W-Y, Yen K-C, Yang K-C, Lin F-H. The use of biotinylated-EGF-modified gelatin nanoparticle carrier to enhance cisplatin accumulation in cancerous lungs via inhalation. Biomaterials 2009; 30(20): 3476-85.
[31]
Tseng C-L, Wu SY-H, Wang W-H, et al. Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials 2008; 29(20): 3014-22.
[32]
Ganesh S, Iyer AK, Morrissey DV, Amiji MM. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors. Biomaterials 2013; 34(13): 3489-502.
[33]
Martinelli F, Balducci AG, Kumar A, et al. Engineered sodium hyaluronate respirable dry powders for pulmonary drug delivery. Int J Pharm 2017; 517(1-2): 286-95.
[34]
Rosiere R, Gelbcke M, Mathieu V, Van Antwerpen P, Amighi K, Wauthoz N. New dry powders for inhalation containing temozolomide-based nanomicelles for improved lung cancer therapy. Int J Oncol 2015; 47(3): 1131-42.
[35]
Rosiere R, Van Woensel M, Mathieu V, et al. Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy. Int J Pharm 2016; 501(1-2): 148-59.
[36]
Rosiere R, Van Woensel M, Gelbcke M, et al. A new folate-grafted chitosan derivative to improve the delivery of paclitaxel-loaded solid lipid nanoparticles for lung tumour therapy by inhalation. Mol Pharm 2018; 15(3): 899-910.
[37]
Zhang M, Kim Y-K, Cui P, et al. Folate-conjugated polyspermine for lung cancer-targeted gene therapy. Acta Pharm Sin B 2016; 6(4): 336-43.
[38]
Luo C-Q, Jang Y, Xing L, et al. Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway. Int J Pharm 2016; 513(1-2): 591-601.
[39]
Choi SH, Byeon HJ, Choi JS, et al. Inhalable self-assembled albumin nanoparticles for treating drug-resistant lung cancer. J Control Release 2015; 197: 199-207.
[40]
Levet V, Rosiere R, Merlos R, et al. Development of controlled-release cisplatin dry powders for inhalation against lung cancers. Int J Pharm 2016; 515(1-2): 209-20.
[41]
Levet V, Merlos R, Rosiere R, Amighi K, Wauthoz N. Platinum pharmacokinetics in mice following inhalation of cisplatin dry powders with different release and lung retention properties. Int J Pharm 2017; 517(1-2): 359-72.
[42]
Kim SY, Naskar D, Kundu SC, et al. Formulation of biologically-inspired silk-based drug carriers for pulmonary delivery targeted for lung cancer. Sci Rep 2015; 5: 11878.
[43]
Rao AK, Shrikhande S, Bajaj A. Development of cisplatin nanoparticles as dry powder inhalers for lung cancer. Curr Nanosci 2013; 9(4): 447-50.
[44]
Cafaggi S, Russo E, Stefani R, et al. Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex. J Control Release 2007; 121(1-2): 110-23.
[45]
Singh DJ, Lohade AA, Parmar JJ, et al. Development of chitosan-based dry powder inhalation system of cisplatin for lung cancer. Indian J Pharm Sci 2012; 74(6): 521-6.
[46]
Zhong Q, Bielski ER, Rodrigues LS, Brown MR, Reineke JJ, da Rocha SRP. Conjugation to poly(amidoamine) dendrimers and pulmonary delivery reduce cardiac accumulation and enhance antitumor activity of doxorubicin in lung metastasis. Mol Pharm 2016; 13(7): 2363-75.
[47]
Varshosaz J, Hassanzadeh F, Mardani A, Rostami M. Feasibility of haloperidol-anchored albumin nanoparticles loaded with doxorubicin as dry powder inhaler for pulmonary delivery. Pharm Dev Technol 2015; 20(2): 183-96.
[48]
Kaminskas LM, McLeod VM, Ryan GM, et al. Pulmonary administration of a doxorubicin-conjugated dendrimer enhances drug exposure to lung metastases and improves cancer therapy. J Control Release 2014; 183: 18-26.
[49]
Azarmi S, Tao X, Chen H, et al. Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm 2006; 319(1-2): 155-61.
[50]
Garbuzenko OB, Mainelis G, Taratula O, Minko T. Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention. Cancer Biol Med 2014; 11(1): 44-55.
[51]
Roa WH, Azarmi S, Al-Hallak MHDK, Finlay WH, Magliocco AM, Lobenberg R. Inhalable nanoparticles, a non-invasive approach to treat lung cancer in a mouse model. J Control Release 2011; 150(1): 49-55.
[52]
Meenach SA, Anderson KW, Zach Hilt J, McGarry RC, Mansour HM. Characterization and aerosol dispersion performance of advanced spray-dried chemotherapeutic PEGylated phospholipid particles for dry powder inhalation delivery in lung cancer. Eur J Pharm Sci 2013; 49(4): 699-711.
[53]
Yang R, Yang S-G, Shim W-S, et al. Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregates. J Pharm Sci 2009; 98(3): 970-84.
[54]
Luo T, Loira-Pastoriza C, Patil HP, et al. PEGylation of paclitaxel largely improves its safety and anti-tumor efficacy following pulmonary delivery in a mouse model of lung carcinoma. J Control Release 2016; 239: 62-71.
[55]
Wang H, Xu Y, Zhou X. Docetaxel-loaded chitosan microspheres as a lung targeted drug delivery system: in vitro and in vivo evaluation. Int J Mol Sci 2014; 15(3): 3519-32.
[56]
Gandhi M, Pandya T, Gandhi R, et al. Inhalable liposomal dry powder of gemcitabine-HCl: Formulation, in vitro characterization and in vivo studies. Int J Pharm 2015; 496(2): 886-95.
[57]
Youngren-Ortiz SR, Hill DB, Hoffmann PR, et al. Development of optimized, inhalable, gemcitabine-loaded gelatin nanocarriers for lung cancer. J Aerosol Med Pulm Drug Deliv 2017; 30(5): 299-321.
[58]
Lee W-H, Loo C-Y, Ong H-X, Traini D, Young PM, Rohanizadeh R. Synthesis and characterization of inhalable flavonoid nanoparticle for lung cancer cell targeting. J Biomed Nanotechnol 2016; 12(2): 371-86.
[59]
Hu L, Kong D, Hu Q, Gao N, Pang S. Evaluation of high-performance curcumin nanocrystals for pulmonary drug delivery both In Vitro and In Vivo. Nanoscale Res Lett 2015; 10(1): 1-9.
[60]
Naseri N, Zakeri-Milani P, Hamishehkar H, Pilehvar-Soltanahmadi Y, Valizadeh H. Development, In Vitro characterization, antitumor and aerosol performance evaluation of respirable prepared by self-nanoemulsification method. Drug Res 2017; 67(6): 343-8.
[61]
Bakhtiary Z, Barar J, Aghanejad A, et al. Microparticles containing erlotinib-loaded solid lipid nanoparticles for treatment of non-small cell lung cancer. Drug Dev Ind Pharm 2017; 43(8): 1244-53.
[62]
Emami J, Pourmashhadi A, Sadeghi H, Varshosaz J, Hamishehkar H. Formulation and optimization of celecoxib-loaded PLGA nanoparticles by the Taguchi design and their in vitro cytotoxicity for lung cancer therapy. Pharm Dev Technol 2015; 20(7): 791-800.
[63]
Dhanda DS, Tyagi P, Mirvish SS, Kompella UB. Supercritical fluid technology based large porous celecoxib-PLGA microparticles do not induce pulmonary fibrosis and sustain drug delivery and efficacy for several weeks following a single dose. J Control Release 2013; 168(3): 239-50.
[64]
Guo XH, Zhang XX, Ye L, et al. Inhalable microspheres embedding chitosan-coated PLGA nanoparticles for 2-methoxyestradiol. J Drug Target 2014; 22(5): 421-7.
[65]
Qiao J-B, Jang Y, Fan Q-Q, et al. Aerosol delivery of biocompatible dihydroergotamine-loaded PLGA-PSPE polymeric micelles for efficient lung cancer therapy. Polym Chem 2017; 8(9): 1540-54.
[66]
Jyoti K, Pandey RS, Kush P, Kaushik D, Jain UK, Madan J. Inhalable bioresponsive chitosan microspheres of doxorubicin and soluble curcumin augmented drug delivery in lung cancer cells. Int J Biol Macromol 2017; 98: 50-8.
[67]
Garbuzenko OB, Winkler J, Tomassone MS, Minko T. Biodegradable janus nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs. Langmuir 2014; 30(43): 12941-9.
[68]
El-Gendy N, Berkland C. Combination chemotherapeutic dry powder aerosols via controlled nanoparticle agglomeration. Pharm Res 2009; 26(7): 1752-63.
[69]
Jinturkar KA, Anish C, Kumar MK, Bagchi T, Panda AK, Misra AR. Liposomal formulations of etoposide and docetaxel for p53 mediated enhanced cytotoxicity in lung cancer cell lines. Biomaterials 2012; 33(8): 2492-507.
[70]
Fulzele Suniket V, Shaik Madhu S, Chatterjee A, Singh M. Anti-cancer effect of celecoxib and aerosolized docetaxel against human non-small cell lung cancer cell line, A549. J Pharm Pharmacol 2006; 58(3): 327-36.
[71]
Haynes A, Shaik Madhu S, Chatterjee A, Singh M. Formulation and evaluation of aerosolized celecoxib for the treatment of lung cancer. Pharm Res 2005; 22(3): 427-39.
[72]
Patel AR, Chougule MB. I.T.; Patlolla, R.; Wang, G.; Singh, M. Efficacy of aerosolized celecoxib encapsulated nanostructured lipid carrier in non-small cell lung cancer in combination with docetaxel. Pharm Res 2013; 30(5): 1435-46.
[73]
Silva AS, Sousa AM, Cabral RP, et al. Aerosolizable gold nano-in-micro dry powder formulations for theragnosis and lung delivery. Int J Pharm 2017; 519(1-2): 240-9.
[74]
Hamzawy MA, Abo-youssef AM, Salem HF, Mohammed SA. Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice. Drug Deliv 2017; 24(1): 599-607.
[75]
Wauthoz N, Deleuze P, Saumet A, Duret C, Kiss R, Amighi K. Temozolomide-based dry powder formulations for lung tumor-related inhalation treatment. Pharm Res 2011; 28(4): 762-75.
[76]
Price DN, Stromberg LR, Kunda NK, Muttil P. In Vivo Pulmonary delivery and magnetic-targeting of dry powder nano-in-microparticles. Mol Pharm 2017; 14(12): 4741-50.
[77]
Zhu L, Li M, Liu X, Du L, Jin Y. Inhalable oridonin-loaded poly(lactic-co-glycolic)acid large porous microparticles for in situ treatment of primary non-small cell lung cancer. Acta Pharm Sin B 2017; 7(1): 80-90.
[78]
Chen Z, Li M, Fan Q, Li W, Duan J. Yuanhuacine dry powder inhaler having anti-lung cancer activity. 2016-11016465, 106420677, 20161118., 2017.
[79]
Chen R, Xu L, Fan Q, et al. Hierarchical pulmonary target nanoparticles via inhaled administration for anticancer drug delivery. Drug Deliv 2017; 24(1): 1191-203.
[80]
Ishiguro S, Alhakamy NA, Uppalapati D, Delzeit J, Berkland CJ, Tamura M. Combined local pulmonary and systemic delivery of AT2R gene by modified TAT peptide nanoparticles attenuates both murine and human lung carcinoma xenografts in mice. J Pharm Sci 2017; 106(1): 385-94.
[81]
Krohn Jensen DM, Cun D, Maltesen MJ, Frokjaer S, Moerck Nielsen H, Foged C. Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation. J Control Release 2010; 142(1): 138-45.
[82]
Yan Y, Zhou K, Xiong H, et al. Aerosol delivery of stabilized polyester-siRNA nanoparticles to silence gene expression in orthotopic lung tumors. Biomaterials 2017; 118: 84-93.
[83]
Jeong EJ, Choi M, Lee J, Rhim T, Lee KY. The spacer arm length in cell-penetrating peptides influences chitosan/siRNA nanoparticle delivery for pulmonary inflammation treatment. Nanoscale 2015; 7(47): 20095-104.
[84]
Okuda T, Kito D, Oiwa A, Fukushima M, Hira D, Okamoto H. Gene silencing in a mouse lung metastasis model by an inhalable dry small interfering RNA powder prepared using the supercritical carbon dioxide technique. Biol Pharm Bull 2013; 36(7): 1183-91.
[85]
Zamora-Avila DE, Zapata-Benavides P, Franco-Molina MA, et al. WT1 gene silencing by aerosol delivery of PEI-RNAi complexes inhibits B16-F10 lung metastases growth. Cancer Gene Ther 2009; 16(12): 892-9.
[86]
Li H-Y, Birchall J. Chitosan-modified dry powder formulations for pulmonary gene delivery. Pharm Res 2006; 23(5): 941-50.
[87]
Okamoto H, Danjo K. Local and systemic delivery of high-molecular weight drugs by powder inhalation. Yakugaku Zasshi 2007; 127(4): 643-53.
[88]
Okamoto H, Nishida S, Todo H, Sakakura Y, Iida K, Danjo K. Pulmonary gene delivery by chitosan-pDNA complex powder prepared by a supercritical carbon dioxide process. J Pharm Sci 2003; 92(2): 371-80.
[89]
Okamoto H, Sakakura Y, Shiraki K, et al. Stability of chitosan-pDNA complex powder prepared by supercritical carbon dioxide process. Int J Pharm 2005; 290(1-2): 73-81.
[90]
Okamoto H, Shiraki K, Yasuda R, Danjo K, Watanabe Y. Chitosan-interferon-β gene complex powder for inhalation treatment of lung metastasis in mice. J Control Release 2011; 150(2): 187-95.
[91]
Dong M, Muerdter TE, Philippi C, et al. Pulmonary delivery and tissue distribution of aerosolized antisense 2′-O-Methyl RNA containing nanoplexes in the isolated perfused and ventilated rat lung. Eur J Pharm Biopharm 2012; 81(3): 478-85.
[92]
Xu C-N, Tian H-Y, Wang Y-B, et al. Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery. Chin Chem Lett 2017; 28(4): 807-12.
[93]
Mainelis G, Seshadri S, Garbuzenko OB, Han T, Wang Z, Minko T. Characterization and application of a nose-only exposure chamber for inhalation delivery of liposomal drugs and nucleic acids to mice. J Aerosol Med Pulm Drug Deliv 2013; 26(6): 345-54.
[94]
Taratula O, Kuzmov A, Shah M, Garbuzenko OB, Minko T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J Control Release 2013; 171(3): 349-57.