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Development, In Vitro Characterization, and In Vivo Toxicity Evaluation of Chitosan-Alginate Nanoporous Carriers Loaded with Cisplatin for Lung Cancer Treatment

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Abstract

Polysaccharide-based aerogels are promising drug carriers. Being nanoporous with a high specific surface area allows their use as a drug vehicle for various delivery routes. Intratracheal and intravenous administration of free cisplatin causes toxicity in the rat liver, lungs, and kidneys. In this work, microspherical particles based on alginate-chitosan without a traditional crosslinker were evaluated for targeted delivery of cisplatin by intratracheal administration. The aerogel particles were prepared using the emulsion gelation method, followed by supercritical carbon dioxide extraction. Loading of cisplatin on the prepared porous particles was performed by impregnation using supercritical fluid technology. The prepared carrier and the loaded drug were evaluated for drug content, release, and in vivo acute and subacute toxicity. Cisplatin was successfully loaded (percent drug loading > 76%) on the prepared carrier (particle size = 0.433 ± 0.091 μm) without chemically interacting with the carrier and without losing its crystal form. Sixty percent of cisplatin was released within 2 h, and the rest was loaded inside the polymer pores and had a sustained first-order release over 6 h. Loading cisplatin on the carrier developed herein reduced the cisplatin lung toxicity but increased the liver toxicity after intratracheal administration with nephrotoxicity being proportional to cisplatin dose in case of carrier-loaded cisplatin. Moreover, loading cisplatin on the carrier significantly reduced mortality rate and prevented weight loss in rats as compared to free cisplatin in subacute studies after intratracheal administration. Thus, the developed carrier showed high potential for targeted delivery of cisplatin for lung cancer treatment by inhalation.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. https://doi.org/10.3322/caac.21442.

    Article  PubMed  Google Scholar 

  2. Didkowska J, Wojciechowska U, Mańczuk M, Łobaszewski J. Lung cancer epidemiology: contemporary and future challenges worldwide. Ann Transl Med. 2016;4:150–60. https://doi.org/10.21037/atm.2016.03.11.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tanley SW, Schreurs AM, Kroon-Batenburg LM, Helliwell JR. Room-temperature X-ray diffraction studies of cisplatin and carboplatin binding to His15 of HEWL after prolonged chemical exposure. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012;68:1300–6. https://doi.org/10.1107/S1744309112042005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Youngren-Ortiz SR, Hill DB, Hoffmann PR, Morris KR, Barrett EG, Forest MG, et al. Development of optimized, inhalable, gemcitabine-loaded gelatin nanocarriers for lung cancer. J Aerosol Med Pulm Drug Deliv. 2017;30:299–321. https://doi.org/10.1089/jamp.2015.1286.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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;171:349–57. https://doi.org/10.1016/j.jconrel.2013.04.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Karra N, Swindle E, Morgan H. Drug delivery for traditional and emerging airway models. Organs-on-a-Chip. 2020;100002:100002. https://doi.org/10.1016/j.ooc.2020.100002.

    Article  Google Scholar 

  7. Patil J, Sarasija S. Pulmonary drug delivery strategies: a concise, systematic review. Lung India. 2012;29:44–9. https://doi.org/10.4103/0970-2113.92361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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. Int J Pharm. 2012;424:98–106. https://doi.org/10.1016/j.ijpharm.2011.12.045.

    Article  CAS  PubMed  Google Scholar 

  9. Ali ME, Lamprecht A. Spray freeze drying for dry powder inhalation of nanoparticles. Eur J Pharm Biopharm. 2014;87:510–7. https://doi.org/10.1016/j.ejpb.2014.03.009.

    Article  CAS  PubMed  Google Scholar 

  10. Alnaief M, Alzaitoun M, García-González C, Smirnova I. Preparation of biodegradable nanoporous microspherical aerogel based on alginate. Carbohydr Polym. 2011;84:1011–8. https://doi.org/10.1016/j.carbpol.2010.12.060.

    Article  CAS  Google Scholar 

  11. Campardelli R, Baldino L, Reverchon E. Supercritical fluids applications in nanomedicine. J Supercrit Fluids. 2015;101:193–214. https://doi.org/10.1016/j.supflu.2015.01.030.

    Article  CAS  Google Scholar 

  12. Obaidat RM, Tashtoush BM, Awad AA, Al Bustami RT. Using supercritical fluid technology (SFT) in preparation of tacrolimus solid dispersions. AAPS PharmSciTech. 2017;18:481–93. https://doi.org/10.1208/s12249-016-0492-4.

    Article  CAS  PubMed  Google Scholar 

  13. García-González C, Uy J, Alnaief M, Smirnova I. Preparation of tailor-made starch-based aerogel microspheres by the emulsion-gelation method. Carbohydr Polym. 2012;88:1378–86. https://doi.org/10.1016/j.carbpol.2012.02.023.

    Article  CAS  Google Scholar 

  14. Marin MA, Mallepally RR, McHugh MA. Silk fibroin aerogels for drug delivery applications. J Supercrit Fluids. 2014;91:84–9. https://doi.org/10.1016/j.supflu.2014.04.014.

    Article  CAS  Google Scholar 

  15. Ulker Z, Erkey C. An advantageous technique to load drugs into aerogels: gas antisolvent crystallization inside the pores. J Supercrit Fluids. 2017;120:310–9. https://doi.org/10.1016/j.supflu.2016.05.033.

    Article  CAS  Google Scholar 

  16. Smola M, Vandamme T, Sokolowski A. Nanocarriers as pulmonary drug delivery systems to treat and to diagnose respiratory and non respiratory diseases. Int J Nanomedicine. 2008;3:1–19.

    Article  CAS  Google Scholar 

  17. Menon JU, Ravikumar P, Pise A, Gyawali D, Hsia CC, Nguyen KT. Polymeric nanoparticles for pulmonary protein and DNA delivery. Acta Biomater. 2014;10:2643–52. https://doi.org/10.1016/j.actbio.2014.01.033.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tahara K, Sakai T, Yamamoto H, Takeuchi H, Hirashima N, Kawashima Y. Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells. Int J Pharm. 2009;382:198–204. https://doi.org/10.1016/j.ijpharm.2009.07.023.

    Article  CAS  PubMed  Google Scholar 

  19. Takka S, Gürel A. Evaluation of chitosan/alginate beads using experimental design: formulation and in vitro characterization. AAPS PharmSciTech. 2010;11:460–6. https://doi.org/10.1208/s12249-010-9406-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jia M, Li Z-B, Chu H-T, Li L, Chen K-Y. Alginate-chitosan microspheres for controlled drug delivery of diltiazem hydrochloride in cardiac diseases. J Biomater Tissue Eng. 2015;5:246–51. https://doi.org/10.1166/jbt.2015.1299.

    Article  Google Scholar 

  21. Chan G, Mooney DJ. Ca2+ released from calcium alginate gels can promote inflammatory responses in vitro and in vivo. Acta Biomater. 2013;9:9281–91. https://doi.org/10.1016/j.actbio.2013.08.002.

    Article  CAS  PubMed  Google Scholar 

  22. Obaidat R, Al-Jbour N, Al-Sou’d K, Sweidan K, Al-Remawi M, Badwan A. Some physico-chemical properties of low molecular weight chitosans and their relationship to conformation in aqueous solution. J Solut Chem. 2010;39:575–88. https://doi.org/10.1007/s10953-010-9517-x.

    Article  CAS  Google Scholar 

  23. Kasaai MR. Calculation of Mark–Houwink–Sakurada (MHS) equation viscometric constants for chitosan in any solvent–temperature system using experimental reported viscometric constants data. Carbohydr Polym. 2007;68:477–88. https://doi.org/10.1016/j.carbpol.2006.11.006.

    Article  CAS  Google Scholar 

  24. Sweidan K, Jaber A-M, Al-jbour N, Obaidat R, Al-Remawi M, Badwan A. Further investigation on the degree of deacetylation of chitosan determined by potentiometric titration. J Excip Food Chem. 2016;2:16–25.

    Google Scholar 

  25. Alnaief M, Obaidat R, Mashaqbeh H. Effect of processing parameters on preparation of carrageenan aerogel microparticles. Carbohydr Polym. 2018;180:264–75. https://doi.org/10.1016/j.carbpol.2017.10.038.

    Article  CAS  PubMed  Google Scholar 

  26. Hassan MS, Lau RWM. Effect of particle shape on dry particle inhalation: study of flowability, aerosolization, and deposition properties. AAPS PharmSciTech. 2009;10:1252–62. https://doi.org/10.1208/s12249-009-9313-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Obaidat RM, Tashtoush BM, Bayan MF, Al Bustami RT, Alnaief M. Drying using supercritical fluid technology as a potential method for preparation of chitosan aerogel microparticles. AAPS PharmSciTech. 2015;16:1235–44. https://doi.org/10.1208/s12249-015-0312-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Alnaief M, Obaidat R, Mashaqbeh H. Loading and evaluation of meloxicam and atorvastatin in carrageenan microspherical aerogels particles. J Appl Pharm Sci. 2019;9:083–8. https://doi.org/10.7324/JAPS.2019.90112.

    Article  CAS  Google Scholar 

  29. Obaidat RM, Alnaief M, Mashaqbeh H. Investigation of carrageenan aerogel microparticles as a potential drug carrier. AAPS PharmSciTech. 2018;19:2226–36. https://doi.org/10.1208/s12249-018-1021-4.

    Article  CAS  PubMed  Google Scholar 

  30. Tsong Y, Hammerstrom T, Chen JJ. Multipoint dissolution specification and acceptance sampling rule based on profile modeling and principal component analysis. J Biopharm Stat. 1997;7:423–39. https://doi.org/10.1080/10543409708835198.

    Article  CAS  PubMed  Google Scholar 

  31. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. https://doi.org/10.1016/0378-5173(83)90064-9.

    Article  CAS  Google Scholar 

  32. Peppas N. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–1.

    CAS  PubMed  Google Scholar 

  33. Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12:263–71. https://doi.org/10.1208/s12248-010-9185-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xie Y, Aillon KL, Cai S, Christian JM, Davies NM, Berkland CJ, et al. Pulmonary delivery of cisplatin–hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer. Int J Pharm. 2010;392:156–63. https://doi.org/10.1016/j.ijpharm.2010.03.058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Fuchs TC, Frick K, Emde B, Czasch S, Landenberg Fv, Hewitt P. Evaluation of novel acute urinary rat kidney toxicity biomarker for subacute toxicity studies in preclinical trials. Toxicol Pathol 2012;40:1031–1048. https://doi.org/10.1177/0192623312444618.

  36. Vhora I, Khatri N, Desai J, Thakkar HP. Caprylate-conjugated cisplatin for the development of novel liposomal formulation. AAPS PharmSciTech. 2014;15:845–57. https://doi.org/10.1208/s12249-014-0106-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Parhizkar M, Reardon PJ, Knowles JC, Browning RJ, Stride E, Barbara PR, et al. Electrohydrodynamic encapsulation of cisplatin in poly (lactic-co-glycolic acid) nanoparticles for controlled drug delivery. Nanomedicine. 2016;12:1919–29. https://doi.org/10.1016/j.nano.2016.05.005.

    Article  CAS  PubMed  Google Scholar 

  38. Abbott WS. A method of computing the effectiveness of an insecticide. J Am Mosq Control Assoc. 1925;18:265–7.

    CAS  Google Scholar 

  39. Edwards DA, Ben-Jebria A, Langer R. Recent advances in pulmonary drug delivery using large, porous inhaled particles. J Appl Physiol. 1998;85:379–85. https://doi.org/10.1152/jappl.1998.85.2.379.

    Article  CAS  PubMed  Google Scholar 

  40. Pham D-D, Grégoire N, Couet W, Gueutin C, Fattal E, Tsapis N. Pulmonary delivery of pyrazinamide-loaded large porous particles. Eur J Pharm Biopharm. 2015;94:241–50. https://doi.org/10.1016/j.ejpb.2015.05.021.

    Article  CAS  PubMed  Google Scholar 

  41. N'Guessan A, Fattal E, Chapron D, Gueutin C, Koffi A, Tsapis N. Dexamethasone palmitate large porous particles: a controlled release formulation for lung delivery of corticosteroids. Eur J Pharm Sci. 2018;113:185–92. https://doi.org/10.1016/j.ejps.2017.09.013.

    Article  CAS  PubMed  Google Scholar 

  42. Ogienko A, Bogdanova E, Trofimov N, Myz S, Ogienko A, Kolesov B, et al. Large porous particles for respiratory drug delivery. Glycine-based formulations. Eur J Pharm Sci. 2017;110:148–56. https://doi.org/10.1016/j.ejps.2017.05.007.

    Article  CAS  PubMed  Google Scholar 

  43. Dhami NK, Pandey RS, Jain UK, Chandra R, Madan J. Non-aggregated protamine-coated poly (lactide-co-glycolide) nanoparticles of cisplatin crossed blood–brain barrier, enhanced drug delivery and improved therapeutic index in glioblastoma cells: in vitro studies. J Microencapsul. 2014;31:685–93. https://doi.org/10.3109/02652048.2014.913725.

    Article  CAS  PubMed  Google Scholar 

  44. Alam N, Khare V, Dubey R, Saneja A, Kushwaha M, Singh G, et al. Biodegradable polymeric system for cisplatin delivery: development, in vitro characterization and investigation of toxicity profile. Mater Sci Eng C Mater Biol Appl. 2014;38:85–93. https://doi.org/10.1016/j.msec.2014.01.043.

    Article  CAS  PubMed  Google Scholar 

  45. Panyam J, Williams D, Dash A, Leslie-Pelecky D, Labhasetwar V. Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. J Pharm Sci. 2004;93:1804–14. https://doi.org/10.1002/jps.20094.

    Article  CAS  PubMed  Google Scholar 

  46. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Control Release. 2004;100:5–28. https://doi.org/10.1016/j.jconrel.2004.08.010.

    Article  CAS  PubMed  Google Scholar 

  47. Maan GK, Bajpai J, Bajpai AK. Investigation of in vitro release of cisplatin from electrostatically crosslinked chitosan-alginate nanoparticles. Synth React Inorg M. 2016;46:1532–40. https://doi.org/10.1080/15533174.2015.1137012.

    Article  CAS  Google Scholar 

  48. Cata JP, Weng H-R, Dougherty PM. Behavioral and electrophysiological studies in rats with cisplatin-induced chemoneuropathy. Brain Res. 2008;1230:91–8. https://doi.org/10.1016/j.brainres.2008.07.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Palipoch S, Punsawad C. Biochemical and histological study of rat liver and kidney injury induced by cisplatin. J Toxicol Pathol. 2013;26:293–9. https://doi.org/10.1293/tox.26.293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kirmani S, Braly PS, McClay EF, Saltztein SL, Plaxe SC, Kim S, et al. A comparison of intravenous versus intraperitoneal chemotherapy for the initial treatment of ovarian cancer. Gynecol Oncol. 1994;54:338–44. https://doi.org/10.1006/gyno.1994.1220.

    Article  CAS  PubMed  Google Scholar 

  51. Geyikoglu F, Isikgoz H, Onalan H, Colak S, Cerig S, Bakir M, et al. Impact of high-dose oleuropein on cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung. J Asian Nat Prod Res. 2017;19:1214–31. https://doi.org/10.1080/10286020.2017.1317751.

    Article  CAS  PubMed  Google Scholar 

  52. Pandey R, Khuller G. Chemotherapeutic potential of alginate–chitosan microspheres as anti-tubercular drug carriers. J Antimicrob Chemother. 2004;53:635–40. https://doi.org/10.1093/jac/dkh139.

    Article  CAS  PubMed  Google Scholar 

  53. Andrade F, Antunes F, Vanessa Nascimento A, Baptista da Silva S, das Neves J, Ferreira D, et al. Chitosan formulations as carriers for therapeutic proteins. Curr Drug Disc Technol 2011;8:157–172. https://doi.org/10.2174/157016311796799035.

  54. Aluani D, Tzankova V, Kondeva-Burdina M, Yordanov Y, Nikolova E, Odzhakov F, et al. Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin. Int J Biol Macromol. 2017;103:771–82. https://doi.org/10.1016/j.ijbiomac.2017.05.062.

    Article  CAS  PubMed  Google Scholar 

  55. Thai H, Nguyen CT, Thach LT, Tran MT, Mai HD, Nguyen TTT, et al. Characterization of chitosan/alginate/lovastatin nanoparticles and investigation of their toxic effects in vitro and in vivo. Sci Rep. 2020;10:1–15. https://doi.org/10.1038/s41598-020-57666-8.

    Article  CAS  Google Scholar 

  56. Uehara T, Yamate J, Torii M, Maruyama T. Comparative nephrotoxicity of cisplatin and nedaplatin: mechanisms and histopathological characteristics. J Toxicol Pathol. 2011;24:87–94. https://doi.org/10.1293/tox.24.87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Dobyan D, Hill D, Lewis T, Bulger R. Cyst formation in rat kidney induced by cis-platinum administration. Lab Investig. 1981;45:260–8.

    CAS  PubMed  Google Scholar 

  58. Sharp CN, Doll MA, Dupre TV, Shah PP, Subathra M, Siow D, et al. Repeated administration of low-dose cisplatin in mice induces fibrosis. Am J Physiol Ren Physiol. 2016;310:F560–F8. https://doi.org/10.1152/ajprenal.00512.2015.

    Article  CAS  Google Scholar 

  59. Campbell KC, Rybak LP, Meech RP, Hughes L. D-methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res. 1996;102:90–8. https://doi.org/10.1016/S0378-5955(96)00152-9.

    Article  CAS  PubMed  Google Scholar 

  60. Tikoo K, Kumar P, Gupta J. Rosiglitazone synergizes anticancer activity of cisplatin and reduces its nephrotoxicity in 7, 12-dimethyl benz {a} anthracene (DMBA) induced breast cancer rats. BMC Cancer. 2009;9:107. https://doi.org/10.1186/1471-2407-9-107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Patil TS, Deshpande AS, Deshpande S, Shende P. Targeting pulmonary tuberculosis using nanocarrier-based dry powder inhalation: current status and futuristic need. J Drug Target. 2019;27:12–27. https://doi.org/10.1080/1061186X.2018.1455842.

    Article  CAS  PubMed  Google Scholar 

  62. Baudron V, Gurikov P, Smirnova I. A continuous approach to the emulsion gelation method for the production of aerogel micro-particle. Colloids Surf A Physicochem Eng Asp. 2019;566:58–69. https://doi.org/10.1016/j.colsurfa.2018.12.055.

    Article  CAS  Google Scholar 

  63. López-Iglesias C, Casielles AM, Altay A, Bettini R, Alvarez-Lorenzo C, García-González CA. From the printer to the lungs: inkjet-printed aerogel particles for pulmonary delivery. Chem Eng J. 2019;357:559–66. https://doi.org/10.1016/j.cej.2018.09.159.

    Article  CAS  Google Scholar 

  64. López-Iglesias C, Barros J, Ardao I, Gurikov P, Monteiro FJ, Smirnova I, et al. Jet cutting technique for the production of chitosan aerogel microparticles loaded with vancomycin. Polymers. 2020;12:273. https://doi.org/10.3390/polym12020273.

    Article  CAS  PubMed Central  Google Scholar 

  65. García-González CA, Budtova T, Durães L, Erkey C, Del Gaudio P, Gurikov P, et al. An opinion paper on aerogels for biomedical and environmental applications. Molecules. 2019;24:1815. https://doi.org/10.3390/molecules24091815.

    Article  CAS  PubMed Central  Google Scholar 

  66. Siepmann J. Future perspectives in pharmaceutics: contributions from younger scientists. Preface Int J Pharm. 2008;364:157–8. https://doi.org/10.1016/j.ijpharm.2008.09.026.

    Article  CAS  PubMed  Google Scholar 

  67. Athamneh T, Amin A, Benke E, Ambrus R, Leopold CS, Gurikov P, et al. Alginate and hybrid alginate-hyaluronic acid aerogel microspheres as potential carrier for pulmonary drug delivery. J Supercrit Fluids. 2019;150:49–55. https://doi.org/10.1016/j.supflu.2019.04.013.

    Article  CAS  Google Scholar 

  68. Raventós M, Duarte S, Alarcón R. Application and possibilities of supercritical CO2 extraction in food processing industry: an overview. Food Sci Technol Int. 2002;8:269–84. https://doi.org/10.1106/108201302029451.

    Article  CAS  Google Scholar 

  69. Lack E, Seidlitz H. Commercial scale decaffeination of coffee and tea using supercritical CO2. Extraction of Natural Products Using Near-Critical Solvents. Springer; 1993. p. 101–139.

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Acknowledgments

The authors acknowledge The Scientific Research Support Fund/Ministry of Higher Education & Scientific Research (Amman, Jordan) for funding this research [project number: MPH/2/15/2013], and Jordan University of Science and Technology (Irbid, Jordan) for all of the facilities, and support provided [local fund number: 121/2016].

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, P. O. Box 3030, Irbid, 22110, Jordan

    Mo’tasem M. Alsmadi & Rana M. Obaidat

  2. Department of Pharmaceutical and Chemical Engineering, Faculty of Applied Medical Sciences, German Jordanian University, Amman, Jordan

    Mohammad Alnaief

  3. Superconductivity & Magnetic Measurements Laboratory, Physics Department, Jordan University of Science and Technology, Irbid, Jordan

    Borhan Aldeen Albiss

  4. Department of Pathology and Public Health, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan

    Nabil Hailat

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Alsmadi, M.M., Obaidat, R.M., Alnaief, M. et al. Development, In Vitro Characterization, and In Vivo Toxicity Evaluation of Chitosan-Alginate Nanoporous Carriers Loaded with Cisplatin for Lung Cancer Treatment. AAPS PharmSciTech 21, 191 (2020). https://doi.org/10.1208/s12249-020-01735-8

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