Inhalable nano-embedded microspheres as an emerging way for local treatment of lung carcinoma: Benefits, Methods of preparation & characterizaton

Dina Mohamed Gaber, Noha Nafee, Osama Y. Abdallah


Lung cancer is the leading cause of cancer deaths worldwide, and this makes it an attractive disease to review and possibly improve therapeutic treatment options. he extreme lethality of lung cancer is ascribed to the lack of early diagnostic strategies as in almost 50 % of the cases the disease is confirmed in stage IV, leaving low chance of survival. The inaccessibility to the deeper portions of the lung for conventional therapy further adds up to the complication in the treatment process. Surgery, radiation, chemotherapy, targeted treatments, and immunotherapy separate or in combination are commonly used to treat lung cancer. However, these treatment types may cause different side effects, and chemotherapy-based regimens appear to have reached a therapeutic plateau. Hence, effective, better- tolerated treatments are needed to address and hopefully overcome this conundrum. Nanocarriers through inhalational route offer many advantages like; 1) they achieve uniform distribution of drug among the alveoli, 2) better solubilization of the drug, 3) sustained drug release which subsequently decreases dosing frequency, 4) better patient compliance, 5) lesser side effects, and 6) improved drug internalization to the cells .Therefore, targeted inhalable NP delivery to the lungs is a potential area of research in cancer nanotechnology that catches the attention of many formulation scientists, oncologists, and biomedical researchers. Based on this literature review, we will discuss the development, characterization, and benefits of inhalable nanocarriers for local treatment of lung carcinoma.


Nanocarriers; lung carcinoma; microparticles

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Conway EM, Pikor LA, Kung SH, Hamilton MJ, Lam S, Lam WL, Bennewith KL. “Macrophages, inflammation, and lung cancer.” American journal of respiratory and critical care medicine. vol. 193, issue, 2, pp. 116-130, Jan 2016.

Ramalingam SS, Owonikoko TK, Khuri FR. “Lung cancer: New biological insights and recent therapeutic advances.” CA: A Cancer Journal for Clinicians, vol. 61, issue 2, pp. 91-112, Feb 2011.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. “Global cancer statistics.” CA: A Cancer Journal for Clinicians, vol. 61, issue 2, pp. 69–90, Feb 2011.

Ahmad J, Akhter S, Rizwanullah M, Amin S, Rahman M, Ahmad MZ, et al. “Nanotechnology-based inhalation treatments for lung cancer: State of the art.” Nanotechnology, Science and Applications, vol. 8, pp. 55-66, Nov 2015.

Wauthoz N, Rosière R, Amighi K. “Inhaled cytotoxic chemotherapy: Clinical challenges, recent developments, and future prospects.” Expert opinion on drug delivery, vol. 18, issue 3, pp. 333-354, Mar 2021.

Kang J-H, Song K-H, Jeong K-C, Kim S, Choi C, Lee CH, et al. “Involvement of Cox-2 in the metastatic potential of chemotherapy-resistant breast cancer cells.” BMC cancer, vol. 11, issue 1, pp. 1-13, Dec 2011.

Otterson GA, Villalona-Calero MA, Sharma S, Kris MG, Imondi A, Gerber M, et al. “Phase I study of inhaled Doxorubicin for patients with metastatic tumors to the lungs.” Clinical Cancer Research, vol. 13, issue 4, pp. 1246-1252, Feb 2007.

Sukumar UK, Bhushan B, Dubey P, Matai I, Sachdev A, Packirisamy G. “Emerging applications of nanoparticles for lung cancer diagnosis and therapy.” International Nano Letters, vol. 3, issue 1, pp. 1-7, Dec 2013.

Lee J, Lee C, Kim TH, Lee ES, Shin BS, Chi S-C, et al. “Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system.” Journal of Controlled Release, vol. 161, issue 3, pp. 728-734, Aug 2012.

Paranjpe M, Muller-Goymann CC. “Nanoparticle-mediated pulmonary drug delivery: A review.” International Journal of Molecular Sciences, vol. 15, issue 4, pp. 5852-5873, Apr 2014.

Mottaghitalab F, Farokhi M, Fatahi Y, Atyabi F, Dinarvand R. “New insights into designing hybrid nanoparticles for lung cancer: Diagnosis and treatment.” Journal of Controlled Release, vol. 295, pp. 250-267, Feb 2019.

Akhter S, Amin S, Ahmad J, Khan S, Anwar M, Ahmad MZ, et al. “Nanotechnology to Combat Multidrug Resistance in Cancer.” Resistance to Targeted ABC Transporters in Cancer, vol. 4, pp. 245-272, 2015.

Tseng C-L, Wu SY-H, Wang W-H, Peng C-L, Lin F-H, Lin C-C, et al. “Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer.” Biomaterials, vol. 29, issue 20, pp. 3014-3022, Jul 2008.

Elsayed I, AbouGhaly MHH. “Inhalable nanocomposite microparticles: preparation, characterization and factors affecting formulation.” Expert Opinion on Drug Delivery, vol. 13, issue 2, pp. 207-222, Feb 2016.

Muralidharan P, Malapit M, Mallory E, Hayes D, Mansour HM. “Inhalable nano-particulate powders for respiratory delivery.” Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 11, issue 5, pp. 1189-1199, Jul 2015.

Lee W-H, Loo C-Y, Traini D, Young PM. “Development and evaluation of paclitaxel and curcumin dry powder for inhalation lung cancer treatment.” Pharmaceutics, vol. 13, issue, pp. 1-19, Jan 2021.

Yang Y, Cheow WS, Hadinoto K. “Dry powder inhaler formulation of lipid–polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.” International Journal of Pharmaceutics, vol. 434, issue 1-2, pp. 49-58, Sep 2012.

Pilcer G, Amighi K. “Formulation strategy and use of excipients in pulmonary drug delivery.” International Journal of Pharmaceutics, vol. 392, issue 1-2, pp. 1-19, Jun 2010.

Yang M, Yamamoto H, Kurashima H, Takeuchi H, Yokoyama T, Tsujimoto H, et al. “Design and evaluation of poly (DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation.” European Journal of Pharmaceutical Sciences, vol. 46, issue 5, pp. 374-380, Aug 2012.

Zhang J, Wu L, Chan HK, Watanabe W. “Formation, characterization, and fate of inhaled drug nanoparticles.” Advanced Drug Delivery Reviews, vol. 63, issue 6, pp. 441–455, May 2011.

Zhou QT, Leung SSY, Tang P, Parumasivam T, Loh ZH, Chan H-K. “Inhaled formulations and pulmonary drug delivery systems for respiratory infections.” Advanced Drug Delivery Reviews, vol. 85, pp. 83-99, May 2015.

Chiang P-C, Hu Y, Blom JD, Thompson DC. “Evaluating the suitability of using rat models for preclinical efficacy and side effects with inhaled corticosteroids nanosuspension formulations.” Nanoscale Research Letters, vol. 5, issue 6, pp. 1010-1019, Jun 2010.

Onoue S, Aoki Y, Kawabata Y, Matsui T, Yamamoto K, Sato H, et al. “Development of inhalable nanocrystalline solid dispersion of tranilast for airway inflammatory diseases.” Journal of Pharmaceutical Sciences, vol. 100, issue 2, pp. 622-633, Feb 2011.

Gradon L, Sosnowski TR. “Formation of particles for dry powder inhalers.” Advanced Powder Technology, vol. 25, issue 1, pp. 43-55, Jan 2014.

Alhajj N, O’Reilly NJ, Cathcart H. “Designing enhanced spray dried particles for inhalation: A review of the impact of excipients and processing parameters on particle properties.” Powder Technology, vol. 384, pp. 313-331, May 2021.

Yu S, Pu X, Ahmed MU, Heidi HY, Mutukuri TT, Li J, et al. “Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa.” International Journal of Pharmaceutics, vol. 610, pp. 121160-121169, Dec 2021.

Cheow WS, Ng MLL, Kho K, Hadinoto K. “Spray-freeze-drying production of thermally sensitive polymeric nanoparticle aggregates for inhaled drug delivery: effect of freeze-drying adjuvants.” International Journal of Pharmaceutics, vol. 404, issue 1, pp. 289-300, Feb 2011.

Wang Y, Kho K, Cheow WS, Hadinoto K. “A comparison between spray drying and spray freeze drying for dry powder inhaler formulation of drug-loaded lipid–polymer hybrid nanoparticles.” International Journal of Pharmaceutics, vol. 424, issue 1-2, pp. 98-106, Mar 2012.

Nahar K, Gupta N, Gauvin R, Absar S, Patel B, Gupta V, et al. “In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals.” European Journal of Pharmaceutical Sciences, vol. 49, issue 5, pp. 805-818, Aug 2013.

Mitchell JP, Nagel MW. “Cascade impactors for the size characterization of aerosols from medical inhalers: their uses and limitations.” Journal of Aerosol Medicine, vol. 16, issue 4, pp. 341-377, Dec 2003.

Chow MYT, Tai W, Chang RYK, Chan H-K, Kwok PCL. “In vitro-in vivo correlation of cascade impactor data for orally inhaled pharmaceutical aerosols.” Advanced Drug Delivery Reviews, vol. 177, pp. 113952-113961, Oct 2021.

Yi D, Price A, Panoskaltsis-Mortari A, Naqwi A, Wiedmann TS. “Measurement of the distribution of aerosols among mouse lobes by fluorescent imaging.” Analytical Biochemistry, vol. 403, issue 1-2, pp. 88-93, Aug 2010.

Mansour HM, Rhee YS, Wu X. “Nanomedicine in pulmonary delivery.” International journal of nanomedicine, vol. 4, pp. 299-319, Dec 2009.

Borchard G, Cassará ML, Roemelé PEH, Florea BI, Junginger HE. “Transport and local metabolism of budesonide and fluticasone propionate in a human bronchial epithelial cell line (Calu-3).” Journal of Pharmaceutical Sciences, vol. 91, issue 6, pp. 1561-1567, Jun 2002.

Selg E, Ewing P, Acevedo F, Sjöberg C-O, Ryrfeldt Å, Gerde P. “Dry powder inhalation exposures of the endotracheally intubated rat lung, ex vivo and in vivo: the pulmonary pharmacokinetics of fluticasone furoate.” Journal of Aerosol Medicine and Pulmonary Drug Delivery, vol. 26, issue 4, pp. 181-189, Aug 2013.

Sakagami M. “In vivo, in vitro and ex vivo models to assess pulmonary absorption and disposition of inhaled therapeutics for systemic delivery.” Advanced Drug Delivery Reviews, vol. 58, issue 9, pp. 1030-1060, Oct. 2006.

Doan TVP, Grégoire N, Lamarche I, Gobin P, Marchand S, Couet W, et al. “A preclinical pharmacokinetic modeling approach to the biopharmaceutical characterization of immediate and microsphere-based sustained release pulmonary formulations of rifampicin.” European Journal of Pharmaceutical Sciences, vol. 48, issue 1, pp. 223-240, Jan 2013.

Rundfeldt C, Steckel H, Scherliess H, Wyska E, Wlaź P. “Inhalable highly concentrated itraconazole nanosuspension for the treatment of bronchopulmonary aspergillosis.” European Journal of Pharmaceutics and Biopharmaceutics, vol. 83, issue 1, pp. 44-53, Jan 2013.

Conde J, Tian F, Hernández Y, Bao C, Cui D, Janssen K-P, et al. “In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models.” Biomaterials, vol. 34, issue 31, pp. 7744-7753, Oct 2013.

Fröhlich E, Salar-Behzadi S. “Toxicological assessment of inhaled nanoparticles: role of in vivo, ex vivo, in vitro, and in silico studies.” International Journal of Molecular Sciences, vol. 15, issue 3, pp. 4795-4822, Mar 2014.



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