Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
권호 표지
DOI QR코드

DOI QR Code

Nanotechnology in reproductive medicine: Opportunities for clinical translation

  • Shandilya, Ruchita (Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health) ;
  • Pathak, Neelam (School of Life Sciences, University of Rajasthan) ;
  • Lohiya, Nirmal Kumar (School of Life Sciences, University of Rajasthan) ;
  • Sharma, Radhey Shyam (Division of Reproductive Biology, Maternal and Child Health, Indian Council of Medical Research) ;
  • Mishra, Pradyumna Kumar (Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health)
  • Received : 2020.03.12
  • Accepted : 2020.06.19
  • Published : 2020.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

In recent years, nanotechnology has revolutionized global healthcare and has been predicted to exert a remarkable effect on clinical medicine. In this context, the clinical use of nanomaterials for cancer diagnosis, fertility preservation, and the management of infertility and other pathologies linked to pubertal development, menopause, sexually transmitted infections, and HIV (human immunodeficiency virus) has substantial promise to fill the existing lacunae in reproductive healthcare. Of late, a number of clinical trials involving the use of nanoparticles for the early detection of reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics have been conducted. However, most of these trials of nanoengineering are still at a nascent stage, and better synergy between pharmaceutics, chemistry, and cutting-edge molecular sciences is needed for effective translation of these interventions from bench to bedside. To bridge the gap between translational outcome and product development, strategic partnerships with the insight and ability to anticipate challenges, as well as an indepth understanding of the molecular pathways involved, are highly essential. Such amalgamations would overcome the regulatory gauntlet and technical hurdles, thereby facilitating the effective clinical translation of these nano-based tools and technologies. The present review comprehensively focuses on emerging applications of nanotechnology, which holds enormous promise for improved therapeutics and early diagnosis of various human reproductive tract diseases and conditions.

Keywords

Acknowledgement

The authors are thankful to the Indian Council of Medical Research (ICMR), Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi, India for funding support to the laboratory of Professor Pradyumna Kumar Mishra.

References

  1. Wilkinson J, Bhattacharya S, Duffy J, Kamath MS, Marjoribanks J, Repping S, et al. Reproductive medicine: still more ART than science? BJOG 2019;126:138-41.
  2. El-Toukhy T. Reproductive medicine in 2020 and beyond. BJOG 2019;126:133-4.
  3. Yurttas Beim P, Parfitt DE, Tan L, Sugarman EA, Hu-Seliger T, Clementi C, et al. At the dawn of personalized reproductive medicine: opportunities and challenges with incorporating multigene panel testing into fertility care. J Assist Reprod Genet 2017;34:1573-6.
  4. Albertini DF. Personalizing reproductive medicine-a biological or technocratic imperative? J Assist Reprod Genet 2017;34:1-2.
  5. Mishra PK, Lohiya NK. Prioritizing reproductive health: can it be the real game changer for India? J Rep Health Med 2016;2:1-3.
  6. Chandra-Mouli V, Akwara E, Engel D, Plessons M, Asnake M, Mehra S, et al. Progress in adolescent sexual and reproductive health and rights globally between 1990 and 2016: what progress has been made, what contributed to this, and what are the implications for the future? Sex Reprod Health Matters 2020;28:1741495.
  7. Huynen I. Editorial for the special issue on "Nanodevices for microwave and millimeter wave applications". Micromachines (Basel) 2020;11:477.
  8. Mishra DK, Shandilya R, Mishra PK. Lipid based nanocarriers: a translational perspective. Nanomedicine 2018;14:2023-50.
  9. Ramos AP, Cruz MAE, Tovani CB, Ciancaglini P. Biomedical applications of nanotechnology. Biophys Rev 2017;9:79-89.
  10. Shandilya R, Bhargava A, Bunkar N, Tiwari R, Goryacheva IY, Mishra PK. Nanobiosensors: point-of-care approaches for cancer diagnostics. Biosens Bioelectron 2019;130:147-65.
  11. Boulaiz H, Alvarez PJ, Ramirez A, Marchal JA, Prados J, Rodriguez-Serrano F, et al. Nanomedicine: application areas and development prospects. Int J Mol Sci 2011;12:3303-21.
  12. Bunkar N, Shandilya R, Bhargava A, Samarth RM, Tiwari R, Mishra DK, et al. Nano-engineered flavonoids for cancer protection. Front Biosci (Landmark Ed) 2019;24:1097-157.
  13. Wong XY, Sena-Torralba A, Alvarez-Diduk R, Muthoosamy K, Merkoci A. Nanomaterials for nanotheranostics: tuning their properties according to disease needs. ACS Nano 2020;14:2585-627.
  14. Mishra DK, Balekar N, Mishra PK. Nanoengineered strategies for siRNA delivery: from target assessment to cancer therapeutic efficacy. Drug Deliv Transl Res 2017;7:346-58.
  15. Patra JK, Das G, Fraceto LF, Campos EV, Rodriguez-Torres MD, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018;16:71.
  16. Chenthamara D, Subramaniam S, Ramakrishnan SG, Krishnaswamy S, Essa MM, Lin FH, et al. Therapeutic efficacy of nanoparticles and routes of administration. Biomater Res 2019;23:20.
  17. Bhargava A, Mishra DK, Jain SK, Srivastava RK, Lohiya NK, Mishra PK. Comparative assessment of lipid based nano-carrier systems for dendritic cell based targeting of tumor re-initiating cells in gynecological cancers. Mol Immunol 2016;79:98-112.
  18. Bhargava A, Srivastava RK, Mishra DK, Tiwari RR, Sharma RS, Mishra PK. Dendritic cell engineering for selective targeting of female reproductive tract cancers. Indian J Med Res 2018;148(Suppl):S50-63.
  19. Harper JC, Aittomaki K, Borry P, Cornel MC, de Wert G, Dondorp W, et al. Recent developments in genetics and medically assisted reproduction: from research to clinical applications. Eur J Hum Genet 2018;26:12-33.
  20. Bunkar N, Pathak N, Lohiya NK, Mishra PK. Epigenetics: a key paradigm in reproductive health. Clin Exp Reprod Med 2016;43:59-81.
  21. Kamel RM. Assisted reproductive technology after the birth of louise brown. J Reprod Infertil 2013;14:96-109.
  22. Yang M, Fan XB, Wu JN, Wang JM. Association of assisted reproductive technology and multiple pregnancies with the risks of birth defects and stillbirth: a retrospective cohort study. Sci Rep 2018;8:8296.
  23. Nagata C, Yang L, Yamamoto-Hanada K, Mezawa H, Ayabe T, Ishizuka K, et al. Complications and adverse outcomes in pregnancy and childbirth among women who conceived by assisted reproductive technologies: a nationwide birth cohort study of Japan environment and children's study. BMC Pregnancy Childbirth 2019;19:77.
  24. Bunkar N, Bhargava A, Chaudhury K, Sharma RS, Lohiya NK, Mishra PK. Fetal nucleic acids in maternal plasma: from biology to clinical translation. Front Biosci (Landmark Ed) 2018;23:397-431.
  25. Kawwass JF, Badell ML. Maternal and fetal risk associated with assisted reproductive technology. Obstet Gynecol 2018;132:763-72.
  26. Palmer SS, Barnhart KT. Biomarkers in reproductive medicine: the promise, and can it be fulfilled? Fertil Steril 2013;99:954-62.
  27. Wahid B, Bashir H, Bilal M, Wahid K, Sumrin A. Developing a deeper insight into reproductive biomarkers. Clin Exp Reprod Med 2017;44:159-70.
  28. Bhargava A, Pathak N, Sharma RS, Lohiya NK, Mishra PK. Environmental impact on reproductive health: can biomarkers offer any help? J Reprod Infertil 2017;18:336-40.
  29. Jha RK, Jha PK, Chaudhury K, Rana SV, Guha SK. An emerging interface between life science and nanotechnology: present status and prospects of reproductive healthcare aided by nano-biotechnology. Nano Rev 2014;5:22762.
  30. Janssen EB, Rijkers AC, Hoppenbrouwers K, Meuleman C, D'Hooghe TM. Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review. Hum Reprod Update 2013;19:570-82.
  31. Friend DR. Drug delivery for the treatment of endometriosis and uterine fibroids. Drug Deliv Transl Res 2017;7:829-39.
  32. Chaudhury K, Babu K N, Singh AK, Das S, Kumar A, Seal S. Mitigation of endometriosis using regenerative cerium oxide nanoparticles. Nanomedicine 2013;9:439-48.
  33. Henriques da Silva J, Borges VR, Pereira Lda C, Ferrari R, de Mattos RM, Barros EG, et al. The oil-resin of the tropical rainforest tree Copaifera langsdorffii reduces cell viability, changes cell morphology and induces cell death in human endometriotic stromal cultures. J Pharm Pharmacol 2015;67:1744-55.
  34. de Almeida Borges VR, Tavares MR, da Silva JH, Tajber L, Boylan F, Ribeiro AF, et al. Development and characterization of poly(lactic-co-glycolic) acid nanoparticles loaded with copaiba oleoresin. Pharm Dev Technol 2018;23:343-50.
  35. Singh AK, Chakravarty B, Chaudhury K. Nanoparticle-assisted combinatorial therapy for effective treatment of endometriosis. J Biomed Nanotechnol 2015;11:789-804.
  36. Guo X, Li W, Zhou J, Hou W, Wen X, Zhang H, et al. Specific photothermal ablation therapy of endometriosis by targeting delivery of gold nanospheres. Small 2017;13:1603270.
  37. Hsu AL, Khachikyan I, Stratton P. Invasive and noninvasive methods for the diagnosis of endometriosis. Clin Obstet Gynecol 2010;53:413-9.
  38. Ferlita A, Battaglia R, Andronico F, Caruso S, Cianci A, Purrello M, et al. Non-coding RNAs in endometrial physiopathology. Int J Mol Sci 2018;19:2120.
  39. Asghari S, Valizadeh A, Aghebati-Maleki L, Nouri M, Yousefi M. Endometriosis: perspective, lights, and shadows of etiology. Biomed Pharmacother 2018;106:163-74.
  40. Laudanski P, Gorodkiewicz E, Ramotowska B, Charkiewicz R, Kuzmicki M, Szamatowicz J. Determination of cathepsins B, D and G concentration in eutopic proliferative endometrium of women with endometriosis by the surface plasmon resonance imaging (SPRI) technique. Eur J Obstet Gynecol Reprod Biol 2013;169:80-3.
  41. Porter KM, Wieser FA, Wilder CL, Sidell N, Platt MO. Cathepsin protease inhibition reduces endometriosis lesion establishment. Reprod Sci 2016;23:623-9.
  42. Grzywa R, Gorodkiewicz E, Burchacka E, Lesner A, Laudanski P, Lukaszewski Z, et al. Determination of cathepsin G in endometrial tissue using a surface plasmon resonance imaging biosensor with tailored phosphonic inhibitor. Eur J Obstet Gynecol Reprod Biol 2014;182:38-42.
  43. Zhang H, Li J, Sun W, Hu Y, Zhang G, Shen M, et al. Hyaluronic acid-modified magnetic iron oxide nanoparticles for MR imaging of surgically induced endometriosis model in rats. PLoS One 2014;9:e94718.
  44. Donnez J, Dolmans MM. Uterine fibroid management: from the present to the future. Hum Reprod Update 2016;22:665-86.
  45. Al-Hendy A, Myers ER, Stewart E. Uterine fibroids: burden and unmet medical need. Semin Reprod Med 2017;35:473-80.
  46. Shalaby SM, Khater MK, Perucho AM, Mohamed SA, Helwa I, Laknaur A, 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;105:1638-48.
  47. Panelli DM, Phillips CH, Brady PC. Incidence, diagnosis and management of tubal and nontubal ectopic pregnancies: a review. Fertil Res Pract 2015;1:15.
  48. Hua S, de Matos MB, Metselaar JM, Storm G. Current trends and challenges in the clinical translation of nanoparticulate nanomedicines: pathways for translational development and commercialization. Front Pharmacol 2018;9:790.
  49. Kaitu'u-Lino TJ, Pattison S, Ye L, Tuohey L, Sluka P, MacDiarmid J, et al. Targeted nanoparticle delivery of doxorubicin into placental tissues to treat ectopic pregnancies. Endocrinology 2013;154:911-9.
  50. Chiu NF, Kuo CT, Chen CY. High-affinity carboxyl-graphene oxide-based SPR aptasensor for the detection of hCG protein in clinical serum samples. Int J Nanomedicine 2019;14:4833-47.
  51. Liao LW, Chen PH, Wang YL. Electrical double layer gated field effect transistor biosensors for the quantitative detection of beta-human chorionic gonadotropin. ECS Trans 2019;92:57-60.
  52. Shaaban AM, Rezvani M, Haroun RR, Kennedy AM, Elsayes KM, Olpin JD, et al. Gestational trophoblastic disease: clinical and imaging features. Radiographics 2017;37:681-700.
  53. Hui P. Gestational trophoblastic tumors: a timely review of diagnostic pathology. Arch Pathol Lab Med 2019;143:65-74.
  54. Zhang B, Zheng M, Cai L, Fan X. Synthesis and characterization of Placental Chondroitin Sulfate A (plCSA): targeting lipid-polymer nanoparticles. J Vis Exp 2018;(139):58209.
  55. Zhang B, Tan L, Yu Y, Wang B, Chen Z, Han J, et al. Placenta-specific drug delivery by trophoblast-targeted nanoparticles in mice. Theranostics 2018;8:2765-81.
  56. Zhang B, Cheng G, Zheng M, Han J, Wang B, Li M, et al. Targeted delivery of doxorubicin by CSA-binding nanoparticles for choriocarcinoma treatment. Drug Deliv 2018;25:461-71.
  57. Dubey V, Nahar M, Mishra D, Mishra P, Jain NK. Surface structured liposomes for site specific delivery of an antiviral agent-indinavir. J Drug Target 2011;19:258-69.
  58. Mishra PK, Raghuram GV, Bhargava A, Pathak N. Translation research in molecular disease diagnosis: bridging gap from laboratory to practice. J Glob Infect Dis 2011;3:205-6.
  59. Antoine TE, Hadigal SR, Yakoub AM, Mishra YK, Bhattacharya P, Haddad C, et al. Intravaginal zinc oxide tetrapod nanoparticles as novel immunoprotective agents against genital herpes. J Immunol 2016;196:4566-75.
  60. Ramyadevi D, Rajan KS, Vedhahari BN, Ruckmani K, Subramanian N. Heterogeneous polymer composite nanoparticles loaded in situ gel for controlled release intra-vaginal therapy of genital herpes. Colloids Surf B Biointerfaces 2016;146:260-70.
  61. Orlowski P, Kowalczyk A, Tomaszewska E, Ranoszek-Soliwoda K, Wegrzyn A, Grzesiak J, et al. Antiviral activity of tannic acid modified silver nanoparticles: potential to activate immune response in herpes genitalis. Viruses 2018;10:524.
  62. Agelidis A, Koujah L, Suryawanshi R, Yadavalli T, Mishra YK, Adelung R, et al. An intra-vaginal Zinc Oxide Tetrapod Nanoparticles (ZOTEN) and genital herpesvirus cocktail can provide a novel platform for live virus vaccine. Front Immunol 2019;10:500.
  63. Ganda IS, Zhong Q, Hali M, Albuquerque RL, Padilha FF, da Rocha SR, et al. Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection. Int J Pharm 2017;527:79-91.
  64. Park MS, Yang YM, Kim JS, Choi EJ. Comparative study of antiretroviral drug regimens and drug-drug interactions between younger and older HIV-infected patients at a tertiary care teaching hospital in South Korea. Ther Clin Risk Manag 2018;14:2229-41.
  65. Mohideen M, Quijano E, Song E, Deng Y, Panse G, Zhang W, et al. Degradable bioadhesive nanoparticles for prolonged intravaginal delivery and retention of elvitegravir. Biomaterials 2017;144:144-54.
  66. Wagner RD, Johnson SJ, Danielsen ZY, Lim JH, Mudalige T, Linder S. Polyethylene glycol-functionalized poly (Lactic Acid-co-Glycolic Acid) and graphene oxide nanoparticles induce pro-inflammatory and apoptotic responses in Candida albicans-infected vaginal epithelial cells. PLoS One 2017;12:e0175250.
  67. Soler M, Belushkin A, Cavallini A, Kebbi-Beghdadi C, Greub G, Altug H. Multiplexed nanoplasmonic biosensor for one-step simultaneous detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine. Biosens Bioelectron 2017;94:560-7.
  68. Kessler R, Hinkle BT, Moyers A, Silverberg B. Adolescent sexual health: identity, risk, and screening for sexually transmitted infections. Prim Care 2020;47:367-82.
  69. Mandal S, Belshan M, Holec A, Zhou Y, Destache CJ. An Enhanced emtricitabine-loaded long-acting nanoformulation for prevention or treatment of HIV infection. Antimicrob Agents Chemother 2016;61:e01475-16.
  70. Kumar P, Lakshmi YS, Kondapi AK. Triple drug combination of zidovudine, efavirenz and lamivudine loaded lactoferrin nanoparticles: an effective nano first-line regimen for HIV therapy. Pharm Res 2017;34:257-68.
  71. Joshy KS, Susan MA, Snigdha S, Nandakumar K, Laly AP, Sabu T. Encapsulation of zidovudine in PF-68 coated alginate conjugate nanoparticles for anti-HIV drug delivery. Int J Biol Macromol 2018;107(Pt A):929-37.
  72. Nayak D, Boxi A, Ashe S, Thathapudi NC, Nayak B. Stavudine loaded gelatin liposomes for HIV therapy: preparation, characterization and in vitro cytotoxic evaluation. Mater Sci Eng C Mater Biol Appl 2017;73:406-16.
  73. Leporati A, Gupta S, Bolotin E, Castillo G, Alfaro J, Gottikh MB, et al. Antiretroviral hydrophobic core graft-copolymer nanoparticles: the effectiveness against mutant HIV-1 strains and in vivo distribution after topical application. Pharm Res 2019;36:73.
  74. Mirani A, Kundaikar H, Velhal S, Patel V, Bandivdekar A, Degani M, et al. Tetrahydrocurcumin-loaded vaginal nanomicrobicide for prophylaxis of HIV/AIDS: in silico study, formulation development, and in vitro evaluation. Drug Deliv Transl Res 2019;9:828-47.
  75. Tyo KM, Lasnik AB, Zhang L, Mahmoud M, Jenson AB, Fuqua JL, et al. Sustained-release Griffithsin nanoparticle-fiber composites against HIV-1 and HSV-2 infections. J Control Release 2020;321:84-99.
  76. Fu X, Cheng Z, Yu J, Choo P, Chen L, Choo J. A SERS-based lateral flow assay biosensor for highly sensitive detection of HIV-1 DNA. Biosens Bioelectron 2016;78:530-7.
  77. Ye YD, Xia L, Xu DD, Xing XJ, Pang DW, Tang HW. DNA-stabilized silver nanoclusters and carbon nanoparticles oxide: A sensitive platform for label-free fluorescence turn-on detection of HIV-DNA sequences. Biosens Bioelectron 2016;85:837-43.
  78. Deng X, Wang C, Gao Y, Li J, Wen W, Zhang X, et al. Applying strand displacement amplification to quantum dots-based fluorescent lateral flow assay strips for HIV-DNA detection. Biosens Bioelectron 2018;105:211-7.
  79. Fang BY, Li C, An J, Zhao SD, Zhuang ZY, Zhao YD, et al. HIV-related DNA detection through switching on hybridized quenched fluorescent DNA-Ag nanoclusters. Nanoscale 2018;10:5532-8.
  80. Kosaka PM, Pini V, Calleja M, Tamayo J. Ultrasensitive detection of HIV-1 p24 antigen by a hybrid nanomechanical-optoplasmonic platform with potential for detecting HIV-1 at first week after infection. PLoS One 2017;12:e0171899.
  81. Chunduri LA, Kurdekar A, Haleyurgirisetty MK, Bulagonda EP, Kamisetti V, Hewlett IK. Femtogram level sensitivity achieved by surface engineered silica nanoparticles in the early detection of HIV infection. Sci Rep 2017;7:7149.
  82. Zhao MD, Sun YM, Fu GF, Du YZ, Chen FY, Yuan H, et al. Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure. Biomaterials 2012;33:634-43.
  83. Wang N, Liu B, Liang L, Wu Y, Xie H, Huang J, et al. Antiangiogenesis therapy of endometriosis using PAMAM as a gene vector in a noninvasive animal model. Biomed Res Int 2014;2014:546479.
  84. Zhao MD, Cheng JL, Yan JJ, Chen FY, Sheng JZ, Sun DL, et al. Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation. Int J Nanomedicine 2016;11:1323-36.
  85. Li T, Chen Q, Zheng Y, Zhang P, Chen X, Lu J, et al. PAMAM-cRGD mediating efficient siRNA delivery to spermatogonial stem cells. Stem Cell Res Ther 2019;10:399.
  86. Patel ND, Parsons JK. Epidemiology and etiology of benign prostatic hyperplasia and bladder outlet obstruction. Indian J Urol 2014;30:170-6.
  87. Lim KB. Epidemiology of clinical benign prostatic hyperplasia. Asian J Urol 2017;4:148-51.
  88. de Sousa VP, Crean J, de Almeida Borges VR, Rodrigues CR, Tajber L, Boylan F, et al. Nanostructured systems containing babassu (Orbignya speciosa) oil as a potential alternative therapy for benign prostatic hyperplasia. Int J Nanomedicine 2013;8:3129-39.
  89. Al-Trad B, Aljabali A, Al Zoubi M, Shehab M, Omari S. Effect of gold nanoparticles treatment on the testosterone-induced benign prostatic hyperplasia in rats. Int J Nanomedicine 2019;14:3145-54.
  90. Krieger JN, Lee SW, Jeon J, Cheah PY, Liong ML, Riley DE. Epidemiology of prostatitis. Int J Antimicrob Agents 2008;31 Suppl 1(Suppl 1):S85-90.
  91. Khan FU, Ihsan AU, Khan HU, Jana R, Wazir J, Khongorzul P, et al. Comprehensive overview of prostatitis. Biomed Pharmacother 2017;94:1064-76.
  92. Cao Y, Cheng Y, Ihsan AU, Khan FU, Xie D, Cui X, et al. A nanoparticle-coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in mice model. Fundam Clin Pharmacol 2019;33:267-76.
  93. Cheng Y, Cao Y, Ihsan AU, Khan FU, Li X, Xie D, et al. Novel treatment of experimental autoimmune prostatitis by nanoparticle-conjugated autoantigen peptide T2. Inflammation 2019;42:1071-81.
  94. Rew KT, Heidelbaugh JJ. Erectile dysfunction. Am Fam Physician 2016;94:820-7.
  95. Yafi FA, Jenkins L, Albersen M, Corona G, Isidori AM, Goldfarb S, et al. Erectile dysfunction. Nat Rev Dis Primers 2016;2:16003.
  96. Kim JH, Lee HJ, Doo SH, Yang WJ, Choi D, Kim JH, et al. Use of nanoparticles to monitor human mesenchymal stem cells transplanted into penile cavernosum of rats with erectile dysfunction. Korean J Urol 2015;56:280-7.
  97. Lin H, Dhanani N, Tseng H, Souza GR, Wang G, Cao Y, et al. Nanoparticle improved stem cell therapy for erectile dysfunction in a rat model of cavernous nerve injury. J Urol 2016;195:788-95.
  98. Tawfik MA, Tadros MI, Mohamed MI. Polyamidoamine (PAMAM) dendrimers as potential release modulators and oral bioavailability enhancers of vardenafil hydrochloride. Pharm Dev Technol 2019;24:293-302.
  99. Fahmy UA. Nanoethosomal transdermal delivery of vardenafil for treatment of erectile dysfunction: optimization, characterization, and in vivo evaluation. Drug Des Devel Ther 2015;9:6129-37.
  100. Badr-Eldin SM, Ahmed OA. Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: ex vivo and in vivo evaluation. Drug Des Devel Ther 2016;10:1323-33.
  101. Ali MF, Salem HF, Abdelmohsen HF, Attia SK. Preparation and clinical evaluation of nano-transferosomes for treatment of erectile dysfunction. Drug Des Devel Ther 2015;9:2431-47.
  102. Kurakula M, Ahmed OA, Fahmy UA, Ahmed TA. Solid lipid nanoparticles for transdermal delivery of avanafil: optimization, formulation, in-vitro and ex-vivo studies. J Liposome Res 2016;26:288-96.
  103. Raj V, Vijayan AN, Joseph K. Naked eye detection of infertility using fructose blue: a novel gold nanoparticle based fructose sensor. Biosens Bioelectron 2014;54:171-4.
  104. Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci 2015;8:191-6.
  105. Moridi H, Hosseini SA, Shateri H, Kheiripour N, Kaki A, Hatami M, et al. Protective effect of cerium oxide nanoparticle on sperm quality and oxidative damage in malathion-induced testicular toxicity in rats: an experimental study. Int J Reprod Biomed 2018;16:261-6.
  106. Chang M, Chang YJ, Wang TY, Yu Q. Sperm movement control utilizing surface charged magnetic nanoparticles. J Nanosci Nanotechnol 2019;19:5713-22.
  107. Vidya R, Saji A. Naked eye detection of infertility based on sperm protamine-induced aggregation of heparin gold nanoparticles. Anal Bioanal Chem 2018;410:3053-8.
  108. Sun Z, Wu S, Ma J, Shi H, Wang L, Sheng A, et al. Colorimetric sensor array for human semen identification designed by coupling zirconium metal-organic frameworks with DNA-modified gold nanoparticles. ACS Appl Mater Interfaces 2019;11:36316-23.
  109. Lohiya NK, Manivannan B, Mishra PK, Pathak N. Vas deferens, a site of male contraception: an overview. Asian J Androl 2001;3:87-95.
  110. Townsend J, Sitruk-Ware R, RamaRao S, Sailer J. Contraceptive technologies for global health: ethically getting to safe, effective and acceptable options for women and men. Drug Deliv Transl Res 2020;10:299-303.
  111. Li H, Garner T, Diaz F, Wong PK. A multiwell microfluidic device for analyzing and screening nonhormonal contraceptive agents. Small 2019;15:e1901910.
  112. Chua BY, Al Kobaisi M, Zeng W, Mainwaring D, Jackson DC. Chitosan microparticles and nanoparticles as biocompatible delivery vehicles for peptide and protein-based immunocontraceptive vaccines. Mol Pharm 2012;9:81-90.
  113. D'Souza AA, Yevate SV, Bandivdekar AH, Devarajan PV. In situ polyethylene sebacate particulate carriers as an alternative to Freund's adjuvant for delivery of a contraceptive peptide vaccine: a feasibility study. Int J Pharm 2015;496:601-8.
  114. Luo J, Liu XL, Zhang Y, Wang YQ, Xu WM, Yang J. The immunogenicity of CRISP1 plasmid-based contraceptive vaccine can be improved when using chitosan nanoparticles as the carrier. Am J Reprod Immunol 2016;75:643-53.
  115. Li WQ, Sun CY, Wang F, Wang YC, Zhai YW, Liang M, et al. Achieving a new controllable male contraception by the photothermal effect of gold nanorods. Nano Lett 2013;13:2477-84.
  116. Xu XX, Ding MH, Zhang JX, Zheng W, Li L, Zheng YF. A novel copper/polydimethiylsiloxane nanocomposite for copper-containing intrauterine contraceptive devices. J Biomed Mater Res B Appl Biomater 2013;101:1428-36.
  117. Chen Y, Luo Y, Jia Z, Jia D, Chen J. Preparation and characterization of silicone rubber/nano-copper nanocomposites for use in intrauterine devices. Biomed Mater Eng 2014;24:1269-74.
  118. Hu LX, Hu SF, Rao M, Yang J, Lei H, Duan Z, et al. Studies of acute and subchronic systemic toxicity associated with a copper/low-density polyethylene nanocomposite intrauterine device. Int J Nanomedicine 2018;13:4913-26.
  119. Bao W, Xie L, Zeng X, Kang H, Wen S, Cui B, et al. A cocktail-inspired male birth control strategy with physical/chemical dual contraceptive effects and remote self-cleared properties. ACS Nano 2019;13:1003-11.
  120. Li W, Tang J, Terry RN, Li S, Brunie A, Callahan RL, et al. Long-acting reversible contraception by effervescent microneedle patch. Sci Adv 2019;5:eaaw8145.
  121. Luna Russo MA, Chalif JN, Falcone T. Clinical management of endometriosis. Minerva Ginecol 2020;72:106-118.
  122. Stewart EA, Laughlin-Tommaso SK, Catherino WH, Lalitkumar S, Gupta D, Vollenhoven B. Uterine fibroids. Nat Rev Dis Primers 2016;2:16043.
  123. De La Cruz MS, Buchanan EM. Uterine fibroids: diagnosis and treatment. Am Fam Physician 2017;95:100-7.
  124. Marion LL, Meeks GR. Ectopic pregnancy: history, incidence, epidemiology, and risk factors. Clin Obstet Gynecol 2012;55:376-86.
  125. Hendriks E, Rosenberg R, Prine L. Ectopic pregnancy: diagnosis and management. Am Fam Physician 2020;101:599-606.
  126. Barkalina N, Charalambous C, Jones C, Coward K. Nanotechnology in reproductive medicine: emerging applications of nanomaterials. Nanomedicine 2014;10:921-38.
  127. Mobley DF, Khera M, Baum N. Recent advances in the treatment of erectile dysfunction. Postgrad Med J 2017;93:679-85.
  128. Irwin GM. Erectile dysfunction. Prim Care 2019;46:249-55.
  129. Leaver RB. Male infertility: an overview of causes and treatment options. Br J Nurs 2016;25:S35-40.
  130. Baskaran S, Finelli R, Agarwal A, Henkel R. Diagnostic value of routine semen analysis in clinical andrology. Andrologia 2020 May 12 [Epub]. https://doi.org/10.1111/and.13614.
  131. Batur P, Bowersox N, McNamara M. Contraception: efficacy, risks, continuation rates, and use in high-risk women. J Womens Health (Larchmt) 2016;25:853-6.
  132. Bedin A, Maranhao RC, Tavares ER, Carvalho PO, Baracat EC, Podgaec S. Nanotechnology for the treatment of deep endometriosis: uptake of lipid core nanoparticles by LDL receptors in endometriotic foci. Clinics (Sao Paulo) 2019;74:e989.
  133. Yuan M, Ding S, Meng T, Lu B, Shao S, Zhang X, et al. Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain. Int J Nanomedicine 2017;12:8171-83.
  134. Moses AS, Taratula OR, Lee H, Luo F, Grenz T, Korzun T, et al. Nanoparticle-based platform for activatable fluorescence imaging and photothermal ablation of endometriosis. Small 2020;16:e1906936.
  135. Jafari Y, Peeling RW, Shivkumar S, Claessens C, Joseph L, Pai NP. Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis. PLoSOne 2013;8:e54695.
  136. Yin YP, Chen XS, Wei WH, Gong KL, Cao WL, Yong G, et al. A dual point-of-care test shows good performance in simultaneously detecting nontreponemal and treponemal antibodies in patients with syphilis: a multisite evaluation study in China. Clin Infect Dis 2013;56:659-65.
  137. Nagata MP, Endo K, Ogata K, Yamanaka K, Egashira J, Katafuchi N, et al. Live births from artificial insemination of microfluidic-sorted bovine spermatozoa characterized by trajectories correlated with fertility. Proc Natl Acad Sci U S A 2018;115:E3087-96.
  138. Janagam DR, Ananthula S, Chaudhry K, Wu L, Mandrell TD, Johnson JR, et al. Injectable In situ forming depot systems for long-acting contraception. Adv Biosyst 2017;1:e1700097.

Cited by

  1. Biocompatible Nanomaterials as an Emerging Technology in Reproductive Health; a Focus on the Male vol.12, 2021, https://doi.org/10.3389/fphys.2021.753686
  2. Navigating the ethics of nanomedicine: are we lost in translation? vol.16, pp.13, 2021, https://doi.org/10.2217/nnm-2021-0054
  3. Metal Oxide Nanoparticles: Evidence of Adverse Effects on the Male Reproductive System vol.22, pp.15, 2020, https://doi.org/10.3390/ijms22158061