سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Rahmanian, Mohsen, Ghazanfary, Samereh, Vatanchian, Mehran, Haghbin, Ali, Oroojalian, Fatemeh. (1404). Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics. , 13(1), 196-209. doi: 10.22038/nmj.2025.86007.2155
Mohsen Rahmanian; Samereh Ghazanfary; Mehran Vatanchian; Ali Haghbin; Fatemeh Oroojalian. "Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics". , 13, 1, 1404, 196-209. doi: 10.22038/nmj.2025.86007.2155
Rahmanian, Mohsen, Ghazanfary, Samereh, Vatanchian, Mehran, Haghbin, Ali, Oroojalian, Fatemeh. (1404). 'Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics', , 13(1), pp. 196-209. doi: 10.22038/nmj.2025.86007.2155
Rahmanian, Mohsen, Ghazanfary, Samereh, Vatanchian, Mehran, Haghbin, Ali, Oroojalian, Fatemeh. Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics. , 1404; 13(1): 196-209. doi: 10.22038/nmj.2025.86007.2155

Unlocking the potential of PLGA/thymoquinone nanoparticles: a promising frontier in asthma therapeutics

Nanomedicine Journal
دوره 13، شماره 1، فروردین 2026، صفحه 196-209    اصل مقاله (1.41 M)
نوع مقاله: Research Paper
شناسه دیجیتال (DOI): 10.22038/nmj.2025.86007.2155
نویسندگان
Mohsen Rahmanian1؛ Samereh Ghazanfary2؛ Mehran Vatanchian3؛ Ali Haghbin4؛ Fatemeh Oroojalian* 2، 5
1School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
2Department of Medical Nanotechnology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
3Department of Anatomical Sciences and Pathology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
4Department of Pediatrics, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
5Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
چکیده
Objective(s): To formulate mPEG-PLGA/Thymoquinone nanoparticles for enhanced biological uptake and therapeutic effectiveness of thymoquinone in asthmatic mice induced with ovalbumin (OVA) administration.
Materials and Methods: mPEG-PLGA/thymoquinone nanoparticles generated using nanoprecipitation were studied for size distribution (dynamic light scattering), in vitro release profile, drug entrapment efficiency (EE), and appearance (scanning electron microscopy). Cytotoxicity assessment via the MTT assay using L929 and RAW 264.7, (a mouse macrophagic cell line) confirmed that the formulation was biocompatible at concentrations up to 1000 µg/m. Drug release was analyzed at 37°C and 25°C over 8 days. In vivo efficacy was evaluated in mice with OVA-induced asthma, measuring OVA-specific IgE and cytokine levels (IL-4, IL-13), and lung histopathology (H&E staining).
Results:The nanoparticles exhibited an average size of 255 nm and EE of 68.16%. In vitro release showed early rapid discharge with a subsequent gradual course. In vivo, mPEG-PLGA/Thymoquinone significantly reduced serum OVA-specific IgE levels and Th2-type cytokines (IL-13 and IL-4) in bronchoalveolar lavage fluid (BALF) compared to PBS and thymoquinone treatments. Histopathological analysis (H&E staining) confirmed that mPEG-PLGA/Thymoquinone significantly reduced perivascular and peribronchial inflammation, edema, and epithelial thickness, demonstrating superior efficacy compared to Dexamethasone and free Thymoquinone in some parameters.
Conclusion: mPEG-PLGA/Thymoquinone nanoparticles provide an effective strategy for enhancing thymoquinone's therapeutic potential in asthma by improving drug delivery, reducing inflammation, and modulating the immune response.
کلیدواژه‌ها
Asthma؛ Nanoparticles؛ Thymoquinone؛ Bronchoalveolar lavage؛ Therapeutics
مراجع
  1. Humbert M. Asthma, a priority for the allergist. Allergy. 2006;61(5):515-517.
  2. Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract. 2017;3:1-11.
  3. Xu M, Dong C. IL‐25 in allergic inflammation. Immunol Rev. 2017;278(1):185-191.
  4. Kudo M, Ishigatsubo Y, Aoki I. Pathology of asthma. Front Microbiol. 2013;4:263.
  5. Koch S, Sopel N, Finotto S, Finotto S. Th9 and other IL-9-producing cells in allergic asthma. Semin Immunopathol; 2017: 39 (1): 55-68.Springer.
  6. Verma M, Liu S, Michalec L, Sripada A, Gorska MM, Alam R. Experimental asthma persists in IL-33 receptor knockout mice because of the emergence of thymic stromal lymphopoietin–driven IL-9+ and IL-13+ type 2 innate lymphoid cell subpopulations. J Allergy Clin Immunol. 2018;142(3):793-803.
  7. Borak J, Lefkowitz R. Bronchial hyperresponsiveness. Occup Med. 2016;66(2):95-105.
  8. Boulet L-P. Airway remodeling in asthma: update on mechanisms and therapeutic approaches. Curr Opin Pulm Med. 2018;24(1):56-62.
  9. Papi A, Blasi F, Canonica GW, Morandi L, Richeldi L, Rossi A. Treatment strategies for asthma: reshaping the concept of asthma management. Allergy Asthma Clin Immunol. 2020;16:1-11.
  10. Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Am J Respir Crit Care Med. 2022;205(1):17-35.
  11. Katsaounou P, Buhl R, Brusselle G, Pfister P, Martínez R, Wahn U, et al. Omalizumab as alternative to chronic use of oral corticosteroids in severe asthma. Respir Med. 2019;150:51-62.
  12. Bårnes CB, Ulrik CS. Asthma and adherence to inhaled corticosteroids: current status and future perspectives. Respir Care. 2015;60(3):455-468.
  13. Volmer T, Effenberger T, Trautner C, Buhl R. Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature. Eur Respir J. 2018;52(4).
  14. Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract. 2013;1(6):558-566.
  15. Cherin P, Marie I, Michallet M, Pelus E, Dantal J, Crave J-C, et al. Management of adverse events in the treatment of patients with immunoglobulin therapy: a review of evidence. Autoimmun Rev. 2016;15(1):71-81.
  16. Moghaddam FA, Ebrahimian M, Oroojalian F, Yazdian-Robati R, Kalalinia F, Tayebi L, et al. Effect of thymoquinone-loaded lipid–polymer nanoparticles as an oral delivery system on anticancer efficiency of doxorubicin. J Nanostruct Chem. 2022:1-12.
  17. Amaral-Machado L, Oliveira WN, Moreira-Oliveira SS, Pereira DT, Alencar EN, Tsapis N, et al. Use of natural products in asthma treatment. Evid Based Complement Alternat Med. 2020;2020(1):1021258.
  18. Kan S, Hariyadi DM, Grainge C, Knight DA, Bartlett NW, Liang M. Airway epithelial-targeted nanoparticles for asthma therapy. Am J Physiol Lung Cell Mol Physiol. 2020;318(3):L500-L509.
  19. Omidi M, Malakoutian M, Choolaei M, Oroojalian F, Haghiralsadat F, Yazdian F. A Label-Free detection of biomolecules using micromechanical biosensors. Chin Phys Lett. 2013;30(6):068701.
  20. Hassanpour S, Behnam B, Baradaran B, Hashemzaei M, Oroojalian F, Mokhtarzadeh A, et al. Carbon based nanomaterials for the detection of narrow therapeutic index pharmaceuticals. Talanta. 2021;221:121610.
  21. Feyziazar M, Amini M, Jahanban-Esfahlan A, Baradaran B, Oroojalian F, Kamrani A, et al. Recent advances on the piezoelectric, electrochemical, and optical biosensors for the detection of protozoan pathogens. TrAC Trends Anal Chem. 2022;157:116803.
  22. Bidar N, Oroojalian F, Baradaran B, Eyvazi S, Amini M, Jebelli A, et al. Monitoring of microRNA using molecular beacons approaches: Recent advances. TrAC Trends Anal Chem. 2020;131:116021.
  23. Andisheh F, Oroojalian F, Shakour N, Ramezani M, Shamsara J, Khodaverdi E, et al. Docetaxel encapsulation in nanoscale assembly micelles of folate-PEG-docetaxel conjugates for targeted fighting against metastatic breast cancer in vitro and in vivo. Int J Pharm. 2021;605:120822.
  24. Beygi M, Oroojalian F, Azizi‐Arani S, Hosseini SS, Mokhtarzadeh A, Kesharwani P, et al. Multifunctional nanotheranostics for overcoming the blood–brain barrier. Adv Funct Mater. 2024;34(19):2310881.
  25. Rahmanian M, Ghahremani A, Kesharwani P, Oroojalian F, Sahebkar A. Nanomedicine innovations in spinal cord injury management: Bridging the gap. Environ Res. 2023;235:116563.
  26. Pishavar E, Oroojalian F, Salmasi Z, Hashemi E, Hashemi M. Recent advances of dendrimer in targeted delivery of drugs and genes to stem cells as cellular vehicles. Biotechnol Prog. 2021;37(4):e3174.
  27. Cao H, Liu L, Wang J, Gong M, Yuan R, Lu J, et al. Effects of rAmb a 1-loaded PLGA-PEG nanoparticles in a murine model of allergic conjunctivitis. Molecules. 2022;27(3):598.
  28. Beygi M, Oroojalian F, Hosseini SS, Mokhtarzadeh A, Kesharwani P, Sahebkar A. Recent progress in functionalized and targeted polymersomes and chimeric polymeric nanotheranostic platforms for cancer therapy. Prog Mater Sci. 2023;140:101209.
  29. Vij N. Synthesis and evaluation of airway-targeted PLGA-PEG nanoparticles for drug delivery in obstructive lung diseases. Nanoparticles in Biology and Medicine: Methods and Protocols: Springer. 2020;147-154.
  30. Darakhshan S, Pour AB, Colagar AH, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95:138-158.
  31. Fatima Shad K, Soubra W, Cordato DJ. The role of thymoquinone, a major constituent of Nigella sativa, in the treatment of inflammatory and infectious diseases. Clin Exp Pharmacol Physiol. 2021;48(11):1445-1453.
  32. El Mezayen R, El Gazzar M, Nicolls MR, Marecki JC, Dreskin SC, Nomiyama H. Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation. Immunol lett. 2006;106(1):72-81.
  33. Kohandel Z, Farkhondeh T, Aschner M, Samarghandian S. Anti-inflammatory effects of thymoquinone and its protective effects against several diseases. Biomed Pharmacother. 2021;138:111492.
  34. El Gazzar M, El Mezayen R, Nicolls MR, Marecki JC, Dreskin SC. Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim Biophys Acta Gen Subj. 2006;1760(7):1088-1095.
  35. Shaterzadeh-Yazdi H, Noorbakhsh M-F, Hayati F, Samarghandian S, Farkhondeh T. Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovasc Haematol Disord Drug Targets. 2018;18(1):52-60.
  36. Ghazanfary S, Rahmanian M, Vatanchian M, Haghbin A, Shakeri F, Oroojalian F. Characterization and Efficacy Evaluation of mPEG-PLGA/Taraxasterol Acetate Nanoparticles as Nano-Therapeutic Agents in Asthma Management. BioNanoScience. 2025;15(1):124.
  37. Cao R, Dong X-W, Jiang J-X, Yan X-F, He J-S, Deng Y-M, et al. M3 muscarinic receptor antagonist bencycloquidium bromide attenuates allergic airway inflammation, hyperresponsiveness and remodeling in mice. Eur J Pharmacol. 2011;655(1-3):83-90.
  38. Venturini CL, Macho A, Arunachalam K, de Almeida DAT, Rosa SIG, Pavan E, et al. Vitexin inhibits inflammation in murine ovalbumin-induced allergic asthma. Biomed Pharmacother. 2018;97:143-151.
  39. Massella D, Celasco E, Salaün F, Ferri A, Barresi AA. Overcoming the limits of flash nanoprecipitation: Effective loading of hydrophilic drug into polymeric nanoparticles with controlled structure. Polymers. 2018;10(10):1092.
  40. Ebrahimian M, Mahvelati F, Malaekeh-Nikouei B, Hashemi E, Oroojalian F, Hashemi M. Bromelain loaded lipid-polymer hybrid nanoparticles for oral delivery: Formulation and characterization. Appl Biochem Biotechnol. 2022;194(8):3733-3748.
  41. Ebrahimpour M, Akhlaghi M, Hemati M, Ghazanfary S, Shahriary S, Ghalekohneh SJ, et al. In vitro evaluation and comparison of anticancer, antimicrobial, and antifungal properties of thyme niosomes containing essential oil. Nanomed J. 2022;9(4).
  42. El-Hammadi MM, Small-Howard AL, Jansen C, Fernández-Arévalo M, Turner H, Martín-Banderas L. Potential use for chronic pain: Poly (Ethylene Glycol)-Poly (Lactic-Co-Glycolic Acid) nanoparticles enhance the effects of Cannabis-Based terpenes on calcium influx in TRPV1-Expressing cells. Int J Pharm. 2022;616:121524.
  43. Pishavar E, Oroojalian F, Ramezani M, Hashemi M. Cholesterol‐conjugated PEGylated PAMAM as an efficient nanocarrier for plasmid encoding interleukin‐12 immunogene delivery toward colon cancer cells. Biotechnol Prog. 2020;36(3):e2952.
  44. Wang W, Zhu R, Xie Q, Li A, Xiao Y, Li K, et al. Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles. Int J Nanomed. 2012:3667-3677.
  45. Yao Y, Zeng Q-X, Deng X-Q, Tang G-N, Guo J-B, Sun Y-Q, et al. Connexin 43 upregulation in mouse lungs during ovalbumin-induced asthma. PLoS One. 2015;10(12):e0144106.
  46. Van Hoecke L, Job ER, Saelens X, Roose K. Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration. Journal of visualized experiments : JoVE. 2017(123).
  47. Jusu S, Obayemi J, Salifu A, Nwazojie C, Uzonwanne V, Odusanya O, et al. Drug-encapsulated blend of PLGA-PEG microspheres: in vitro and in vivo study of the effects of localized/targeted drug delivery on the treatment of triple-negative breast cancer. Sci Rep. 2020;10(1):14188.
  48. Ullah S, Shah MR, Shoaib M, Imran M, Elhissi AM, Ahmad F, et al. Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin. Drug Deliv. 2016;23(9):3480-3491.
  49. Fahmy SA, Mahdy NK, Al Mulla H, ElMeshad AN, Issa MY, Azzazy HME-S. PLGA/PEG nanoparticles loaded with cyclodextrin-Peganum harmala alkaloid complex and ascorbic acid with promising antimicrobial activities. Pharmaceutics. 2022;14(1):142.
  50. Noor NS, Kaus NHM, Szewczuk MR, Hamid SBS. Formulation, Characterization and Cytotoxicity Effects of Novel Thymoquinone-PLGA-PF68 Nanoparticles. Int J Mol Sci. 2021;22(17).
  51. Sockrider M, Fussner L. What Is Asthma? Am J Respir Crit Care Med. 2020;202(9):P25-p26.
  52. Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol. 2015;28(1):295-304.
  53. Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge. Disease Models & Mechanisms. 2008;1(4-5):213-220.
  54. Swider E, Koshkina O, Tel J, Cruz LJ, de Vries IJM, Srinivas M. Customizing poly(lactic-co-glycolic acid) particles for biomedical applications. Acta Biomaterialia. 2018;73:38-51.
  55. Essa D, Kondiah PPD, Choonara YE, Pillay V. The Design of Poly(lactide-co-glycolide) Nanocarriers for Medical Applications. Front Bioeng Biotechnol. 2020;8:48.
  56. El-Hammadi MM, Arias JL. Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines. Nanomaterials (Basel, Switzerland). 2022;12(3).
  57. Guo X, Zuo X, Zhou Z, Gu Y, Zheng H, Wang X, et al. PLGA-Based Micro/Nanoparticles: An Overview of Their Applications in Respiratory Diseases. Int J Mol Sci. 2023;24(5).
  58. Li J, Zheng H, Xu E-Y, Moehwald M, Chen L, Zhang X, et al. Inhalable PLGA microspheres: Tunable lung retention and systemic exposure via polyethylene glycol modification. Acta Biomaterialia. 2021;123:325-334.
  59. Xiao X, Zeng X, Zhang X, Ma L, Liu X, Yu H, et al. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma. Int J Nanomed. 2013:4553-4562.
  60. Vllasaliu D, Fowler R, Stolnik S. PEGylated nanomedicines: recent progress and remaining concerns. Expert Opin Drug Deliv. 2014;11(1):139-154.
  61. Owens DE, 3rd, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93-102.
  62. Perry JL, Reuter KG, Kai MP, Herlihy KP, Jones SW, Luft JC, et al. PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macrophage association, biodistribution, and pharmacokinetics. Nano lett. 2012;12(10):5304-5310.
  63. Schneider CS, Xu Q, Boylan NJ, Chisholm J, Tang BC, Schuster BS, et al. Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation. Sci Adv. 2017;3(4):e1601556.
  64. Levy ML, Bacharier LB, Bateman E, Boulet L-P, Brightling C, Buhl R, et al. Key recommendations for primary care from the 2022 Global Initiative for Asthma (GINA) update. NPJ Prim Care Respir Med. 2023;33(1):1-13.
  65. Gour N, Wills-Karp M. IL-4 and IL-13 signaling in allergic airway disease. Cytokine. 2015;75(1):68-78.
  66. Fahy JV. Reducing IgE levels as a strategy for the treatment of asthma. Clin Exp Allergy : journal of the British Society for Allergy and Clinical Immunology. 2000;30 Suppl 1:16-21.
  67. Tanaka A, Jinno M, Hirai K, Miyata Y, Mizuma H, Yamaguchi M, et al. Longitudinal increase in total IgE levels in patients with adult asthma: an association with poor asthma control. Respir Med. 2014;15(1):144.
 

آمار
تعداد مشاهده مقاله: 418
تعداد دریافت فایل اصل مقاله: 253