Nanoparticle-Based Therapeutics for Disorders of the Female Upper Genital Tract: A Comprehensive Review
Abstract
The female reproductive system is susceptible to a range of disorders, including uterine fibroids, endometriosis, polycystic ovarian syndrome (PCOS), and various gynecological cancers. Traditional drug delivery methods often face challenges such as limited bioavailability, systemic side effects, and poor targeting due to biological barriers like mucus layers, fluctuating pH, and immune responses. Nanotechnology offers a transformative approach to overcome these limitations by enabling site-specific and controlled drug release. This review explores the anatomy of the female upper genital tract (UGT), common associated disorders, and the barriers that hinder effective drug delivery. It highlights the potential of nanoparticle-based drug delivery systems—such as liposomes, polymeric nanoparticles, dendrimers, and nanoemulsions—to improve therapeutic outcomes. Nanoparticles can penetrate mucosal barriers, increase drug retention time, and allow targeted therapy through surface modification and responsive release mechanisms. Specific applications of nanocarriers in treating cervical, ovarian, and endometrial cancers, as well as non-malignant conditions like PCOS, fibroids, and salpingemphraxis, are discussed in detail. Examples include gold and zinc oxide nanoparticles for cancer treatment, curcumin-loaded NPs for PCOS, and magnetic NPs for targeted gene delivery. Despite promising preclinical results, concerns regarding toxicity, hormonal disruption, and regulatory challenges remain and warrant further clinical evaluation. In conclusion, nanotechnology holds immense potential to revolutionize female reproductive healthcare by offering non-invasive, efficient, and safer alternatives to conventional therapies. Continued interdisciplinary research is essential to translate these innovations into clinically viable treatments for improving women’s reproductive health outcomes.
Keywords: Nanoparticles, mucosal barriers, cancer treatment.
Keywords:
Nanoparticles, Genital disorder, Mucosal barrier, Cancer treatmentDOI
https://doi.org/10.22270/jddt.v15i8.7313References
1. Chen YJ, Wang CH, Huang CY, Chen KY, Chen YH. The application of nanomedicine in female reproductive health: a systematic review. Int J Environ Res Public Health. 2022;19(21):13748.
2. Van Staden D, Gerber M, Lemmer HJR. The Application of Nano Drug Delivery Systems in Female Upper Genital Tract Disorders. Pharmaceutics. 2024 Nov 19;16(11):1475. https://doi.org/10.3390/pharmaceutics16111475 PMid:39598598 PMCid:PMC11597179
3. Luo X, Jia K, Xing J, Yi J. The utilization of nanotechnology in the female reproductive system and related disorders. Heliyon. 2024 Feb 1;10(3):e25477. https://doi.org/10.1016/j.heliyon.2024.e25477 PMid:38333849 PMCid:PMC10850912
4. Joudeh N, Linke D. Nanoparticle classification, physicochemical properties, characterization, and applications: a comprehensive review for biologists. Jr Nanobiotechnology. 2022 Jun 7;20(1):262. https://doi.org/10.1186/s12951-022-01477-8 PMid:35672712 PMCid:PMC9171489
5. Altammar KA. A review on nanoparticles: characteristics, synthesis, applications, and challenges. Front Microbiol. 2023 Apr 17;14:1155622. https://doi.org/10.3389/fmicb.2023.1155622 PMid:37180257 PMCid:PMC10168541
6. Kumari S, Sarkar L. A review on nanoparticles: structure, classification, synthesis & applications. J Sci Res. 2021 Oct;65(8):42-46. https://doi.org/10.37398/JSR.2021.650809
7. Mohanraj VJ, Chen Y. Nanoparticles - a review. Trop J Pharm Res. 2006 Jul;5(1):561-573. https://doi.org/10.4314/tjpr.v5i1.14634
8. Enazy SA, Kirschen GW, Vincent K, Yang J, Saada J, Shah M, et al. PEGylated polymeric nanoparticles loaded with 2-methoxyestradiol for the treatment of uterine leiomyoma in a patient-derived xenograft mouse model. J Pharm Sci. 2023 Sep;112(9):2552-60. https://doi.org/10.1016/j.xphs.2023.07.018 PMid:37482124 PMCid:PMC10529399
9. Freytag D, Günther V, Maass N, Alkatout I. Uterine fibroids and infertility. Diagnostics. 2021;11(8):1455. https://doi.org/10.3390/diagnostics11081455 PMid:34441389 PMCid:PMC8391505
10. Talukdar S, Singh SK, Mishra MK, Singh R. Emerging Trends in Nanotechnology for Endometriosis: Diagnosis to Therapy. Nanomaterials (Basel). 2024 Jun 5;14(11):976. https://doi.org/10.3390/nano14110976 PMid:38869601 PMCid:PMC11173792
11. Yang L, Yao C, Su Z, Fang Y, Pandey NK, et al. Combination of disulfiram and Copper-Cysteamine nanoparticles induces mitochondria damage and promotes apoptosis in endometrial cancer. Bioact Mater. 2024;36:96-111. https://doi.org/10.1016/j.bioactmat.2024.02.009 PMid:38440322 PMCid:PMC10911931
12. Ramezani Farani M, Azarian M, Heydari Sheikh Hossein H, Abdolvahabi Z, et al. Folic acid-adorned curcumin-loaded iron oxide nanoparticles for cervical cancer. ACS Appl Bio Mater. 2022;5(3):1305-18. https://doi.org/10.1021/acsabm.1c01311 PMid:35201760 PMCid:PMC8941513
13. Gupta KK, Gupta VK, Naumann RW. Ovarian cancer: screening and future directions. Int J Gynecol Cancer. 2019 Jan;29(1):195-200. https://doi.org/10.1136/ijgc-2018-000016 PMid:30640704
14. Quijia CR, Lima C, Silva C, Alves RC, Frem R, Chorilli M. Application of MIL-100(Fe) in drug delivery and biomedicine. Biocatal Agric Biotechnol. 2021;38:102217. https://doi.org/10.1016/j.jddst.2020.102217
15. Lu Y, Manshadi MKD, Rahman M, Lim G, Saadat M, Mohammadi M, et al. Therapeutic efficacy of nanoparticles and routes of administration: advancements and limitations. Biomater Res. 2019;23:16. https://doi.org/10.1186/s40824-019-0166-x PMid:31832232 PMCid:PMC6869321
16. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57. https://doi.org/10.3390/pharmaceutics10020057 PMid:29783687 PMCid:PMC6027495
17. Kadian R. Nanoparticles: A promising drug delivery approach. Asian J Pharm Clin Res. 2018;11(1):30-35. https://doi.org/10.22159/ajpcr.2018.v11i1.22035
18. Iqbal Z, Dilnawaz F. Nanocarriers for vaginal drug delivery. Recent Pat Drug Deliv Formul. 2019;13(1):3-15. https://doi.org/10.2174/1872211313666190215141507 PMid:30767755
19. Leyva-Gómez G, Piñón-Segundo E, Mendoza-Muñoz N, Zambrano-Zaragoza ML, Mendoza-Elvira S, Quintanar-Guerrero D. Approaches in polymeric nanoparticles for vaginal drug delivery: a review of the state of the art. Int J Mol Sci. 2018;19(6):1549. https://doi.org/10.3390/ijms19061549 PMid:29882846 PMCid:PMC6032388
20. Sharma, P.; Patnala, K.; Sah, N.; Deb, V.K.; Gopal, N.; Chauhan, N.; et al. Revamping Precision Treatment with Nanoparticles Envisaging Effective Drug Delivery Systems for Ovarian Cancer. Process Biochem. 2024, 138, 33-46. https://doi.org/10.1016/j.procbio.2023.12.020
21. Anjum, S.; Hashim, M.; Malik, S.A.; Khan, M.; Lorenzo, J.M.; et al. Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment. Cancers 2021, 13, 4570. https://doi.org/10.3390/cancers13184570 PMid:34572797 PMCid:PMC8468934
22. Saber, M.; Hayaei-Tehrani, R.-S.; Mokhtari, S.; Hoorzad, P.; Esfandiari, F. In Vitro Cytotoxicity of Zinc Oxide Nanoparticles in Mouse Ovarian Germ Cells. Toxicol. Vitr. 2021, 70, 105032. https://doi.org/10.1016/j.tiv.2020.105032 PMid:33098963
23. Bhardwaj M, Saxena DC. Preparation of organic and inorganic nanoparticles and their subsequent application in nanocomposites for food packaging systems: A review. Indian J Sci Technol. 2017;10(31):1-9. https://doi.org/10.17485/ijst/2017/v10i31/113864
24. Natesan V, Kim SJ. The Trend of Organic Based Nanoparticles in the Treatment of Diabetes and Its Perspectives. Biomol Ther (Seoul). 2022 Sep 20;31(1):16-26. https://doi.org/10.4062/biomolther.2022.080 PMid:36122910 PMCid:PMC9810454
25. Kumar A, Shahvej S, Yadav P, Modi U, Yadav AK, Solanki R, Bhatia D. Clinical Applications of Targeted Nanomaterials. Pharmaceutics. 2025;17(3):379. https://doi.org/10.3390/pharmaceutics17030379 PMid:40143042 PMCid:PMC11944548
26. Ensign LM, Cone R, Hanes J. Nanoparticle-based drug delivery to the vagina: a review. J Control Release. 2014 Sep 28;190:500-14. https://doi.org/10.1016/j.jconrel.2014.04.033 PMid:24830303 PMCid:PMC4142075
27. Agrahari V, Burnett A, Zhang C, Mitra AK. Nanomedicine in the treatment of cervical cancer: a review. J Biomed Nanotechnol. 2013 Jun;9(6):951-70.
28. Xie H, Yao C, Wang L, Kang Y, Huang Y, Jiang Y, et al. Advances in nanoparticle-based drug delivery systems for female reproductive disorders. Front Pharmacol. 2023;14:1132839.
29. Hou C-C, Zhu J-Q. Nanoparticles and female reproductive system: how do nanoparticles affect oogenesis and embryonic development. Oncotarget. 2017 Jul;8(65):109799-817. https://doi.org/10.18632/oncotarget.19087 PMid:29312650 PMCid:PMC5752563
30. Au A, Mojadadi AB, Shao J Y, Witting P. Physiological benefits of novel selenium delivery via nanoparticles-minimizing oxidative stress to enhance oocyte maturation and developmental competence. Int J Mol Sci. 2023;24(3):https://doi.org/10.3390/ijms24076068 PMid:37047040 PMCid:PMC10094732
31. Lakshmanan M, Saini M, Nune M. Exploring the innovative application of cerium oxide nanoparticles for addressing oxidative stress in ovarian tissue regeneration. J Ovarian Res. 2024;17(1):241. https://doi.org/10.1186/s13048-024-01566-2 PMid:39633503 PMCid:PMC11619646
32. Zhang Y, Wang X, Gu Q, Lu C, Zhao Y, Li X. Two in one: multifunctional poloxamer hydrogel accelerates endometrial regeneration and fertility restoration through synergistic regulation of KGF 2 and NO. Regen Biomater. 2025;12:rbaf062. https://doi.org/10.1093/rb/rbaf062 PMid:40708704 PMCid:PMC12288958
33. Lulseged BA, Ruba A, Ramchandani M, Lei J, Yu X, Sardar R. Iron oxide-based magnetic nanoparticles encapsulated in PEG-PCL nanocarriers target endometriotic tissue in mouse models. Molecules. 2024;29(9):2095. https://doi.org/10.3390/molecules29092095 PMid:38731586 PMCid:PMC11085148
34. Chen JY, Li Y, Sun JH, Tan CP, Ji LN, Mao ZW. Nanotechnology in the management of cervical cancer. Rev Med Virol. 2015;25 Suppl 1(S1):72-83. https://doi.org/10.1002/rmv.1825 PMid:25752817
35. Yao S, Li L, Su X, Wang K, Lu Z, Yuan C, et al. Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo. J Exp Clin Cancer Res. 2018;37:29. https://doi.org/10.1186/s13046-018-0700-z PMid:29478415 PMCid:PMC6389131
36. Zhang Y, Tian J. Strategies, challenges, and prospects of nanoparticles in gynecological malignancies. ACS Omega. 2024;9(31):37504-15. https://doi.org/10.1021/acsomega.4c04573 PMid:39281920 PMCid:PMC11391544
37. Wang S, Huang P, Chen X. Stimuli-responsive programmed specific targeting in nanomedicine. ACS Nano. 2016;10(3):2991-4. https://doi.org/10.1021/acsnano.6b00870 PMid:26881288 PMCid:PMC5223089
38. Velmurugan S, Ganesan K, Rajasundaram A, Thangam C, Cyril R, Subbaraj G. Nanoparticles and the vaginal microbiota: diagnostic and therapeutic innovations in human papillomavirus-associated cervical cancer - a systematic review. Niger Postgrad Med J. 2025;32(1):1-13. https://doi.org/10.4103/npmj.npmj_265_24 PMid:40091465
39. Liang C, Ding J, Yang C, Hu Y, Luo L, Yu B, et al. Synthetically lethal nanoparticles for treatment of endometrial cancer. Nat Nanotechnol. 2018;13(1):72-81. https://doi.org/10.1038/s41565-017-0009-7 PMid:29203914 PMCid:PMC5762267
40. Ding J, Xiao C, Li Y, Cheng H, Wang Y, Cheng Y, et al. Reactive oxygen species-sensitive nanoparticles for co-delivery of paclitaxel and navitoclax to enhance cancer therapy. Int J Nanomedicine. 2020;15:10257-70.
41. Ebeid K, Meng X, Thiel KW, Dooley M, Lyle LT, Raj S, et al. PLGA nanoparticles enhance the cytotoxicity of combination therapy against uterine serous carcinoma via synthetic lethality. Nat Nanotechnol. 2018;13(1):72-81. https://doi.org/10.1038/s41565-017-0009-7 PMid:29203914 PMCid:PMC5762267
42. Manshadi MKD, Saadat M, Mohammadi M, Asadi S, Yousefi G, Karimi R, et al. Dual-responsive magnetic nanomicelles for enhanced chemo-magnetothermal therapy. Int J Nanomedicine. 2023;18:3491-50.
43. Ahmad N, Alhadlaq HA, Alshamsan A, Wahab R, Ahmed F, Arshad M, et al. Thymoquinone-stabilized selenium nanoparticles induce cytotoxicity and cell cycle arrest in HEC1B endometrial cancer cells. ACS Omega. 2023;8(4):3830-8.
44. Bhattacharya S, Anjum MM, Patel KK. Gemcitabine-loaded cationic chitosan-polysarcosine nanoparticles conjugated with EGFRvIII for ovarian cancer targeting. Drug Deliv. 2022;29(1):666-77. https://doi.org/10.1080/10717544.2022.2058645 PMid:35363113 PMCid:PMC8979509
45. Ray S, Singh AN, Shafat S, Baghel DS, Kumar B, Panday NK, et al. Nanostructured lipid carriers with dual targeting for treatment of ovarian cancer. Indian J Pharm Sci. 2024;86(6):1948-57. https://doi.org/10.36468/pharmaceutical-sciences.1462
46. Enazy SA, Kirschen GW, Vincent K, Wang K, Crispens MA, Yang L, et al. PEGylated polymeric nanoparticles loaded with 2-methoxyestradiol for the treatment of uterine leiomyoma in a patient-derived xenograft mouse model. J Pharm Sci. 2023;112(9):2552-60. https://doi.org/10.1016/j.xphs.2023.07.018 PMid:37482124 PMCid:PMC10529399
47. Shalaby SM, Khater MK, Perucho AM, Dick GM, Hassan ME, Diamond MP, et al. Magnetic nanoparticles as a new approach to improve the efficacy of gene therapy against differentiated human uterine fibroid cells and tumor-initiating stem cells. Fertil Steril. 2016;105(6):1638-48.e8. https://doi.org/10.1016/j.fertnstert.2016.03.001 PMid:27020169 PMCid:PMC4971775
48. Borahay MA, Asoglu MR, Mas A, Kilic GS, Al-Hendy A. Nanomedicine applications in uterine fibroids: a systematic review. Reprod Sci. 2020;27(3):635-42.
49. Singh B, Dheer D, Vats A, et al. Nanotechnology approaches for the treatment of polycystic ovary syndrome: current status and future prospects. J Drug Target. 2021;29(9):927-39.
50. Rani P, Kumar P, Kumari P. Curcumin-loaded nanoparticles as a therapeutic intervention for polycystic ovary syndrome: mechanistic insights and future perspectives. Int J Nanomedicine. 2023; 18:1127-38.
51. Sharma A, Gupta N, Malik A. MicroRNA-loaded nanoparticles: emerging therapy for PCOS. Mol Ther Nucleic Acids. 2022; 27:1023-35.
52. Sharma R, Saini V, Taneja G. Magnetic nanoparticles for targeted treatment of tubal infertility: emerging trends. Int J Nanomedicine. 2022; 17:1537-46.
53. Gupta M, Yadav A, Kumar A. Chitosan nanoparticles for site-specific delivery in tubal blockages: a novel approach to treating salpingitis. J Drug Deliv Sci Technol. 2023; 78:104009.
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