Nanocarriers For Vaginal Drug Delivery

Author(s): Zeenat Iqbal, Fahima Dilnawaz*.

Journal Name: Recent Patents on Drug Delivery & Formulation

Volume 13 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: Vaginal drug delivery approach represents one of the imperative strategies for local and systemic delivery of drugs. The peculiar dense vascular networks, mucus permeability, and range of physiological characteristics of the vaginal cavity have been exploited for therapeutic benefit. Furthermore, the vaginal drug delivery has been curtailed due to the influence of different physiological factors like acidic pH, constant cervical secretion, microflora, cyclic changes during periods along with turnover of mucus of varying thickness.

Objective: This review highlights advancement of nanomedicine and its prospective progress towards the clinic.

Methods: Relevant literature reports and patents related to topics are retrieved and used.

Result: The extensive literature search and patent revealed that nanocarriers are efficacious over conventional treatment approaches.

Conclusion: Recently, nanotechnology based drug delivery approach has promised better therapeutic outcomes by providing enhanced permeation and sustained drug release activity. Different nanoplatforms based on drugs, peptides, proteins, antigens, hormones, nucleic material, and microbicides are gaining momentum for vaginal therapeutics.

Keywords: Nanotechnology, nanocarriers, vaginal drug delivery, vaginal barriers, mucoadhesion, vaginal therapeutics.

Haddish-Berhane N, Haghighi K. The role of multiscale computational approaches for rational design of conventional and nanoparticle oral drug delivery systems. Int J Nanomedicine 2007; 2: 315-31.
Major IC. McConville. Vaginal drug delivery for the localised treatment of cervical cancer. Drug Deliv Transl Res 2017; 7: 817-28.
E. Cicinelli, De Ziegler D. New hypotheses. Transvaginal progesterone: Evidence for a new functional ‘portal system’ flowing from the vagina to the uterus. Hum Reprod Update 1999; 5: 365-72.
Hussain A, Ahsan F. The vagina as a route for systemic drug delivery. J Control Release 2005; 103: 301-13.
Paavonen J. Physiology and ecology of the vagina. Scand J Infect Dis Suppl 1983; 40: 31-5.
Bergh PA. Vaginal changes with aging.The gynecologist and the older patient Red Breen JL Rockville MD:. vol. Aspen Publishers., p. 299, 1988.
Ensign LM, Cone R, Hanes J. Nanoparticle-based drug delivery to the vagina: A review. J Control Release 2014; 190: 500-14.
Ashok V, Kumar RM, Murali D, et al. A review on vaginal route as a systemic drug delivery. Crit Rev Pharm Sci 2012; 1: 1-19.
Cone RA. Barrier properties of mucus. Adv Drug Deliv Rev 2009; 61: 75-85.
Boegh M, Nielsen HM. Mucus as a barrier to drug delivery - understanding and mimicking the barrier properties. Basic Clin Pharmacol Toxicol 2015; 116: 179-86.
Linden SK, Saton P, Karlsson NG, Korolik V, McGuckin MA. Mucins in the mucosal barrier to infection. Mucosal Immunol 2008; 1: 183-97.
Audie TDJP, Pigny P, Buisine MP, Janin A, Aubert JP, Porchet N, et al. Mucin gene expression in the human endocervix. Hum Reprod 1995; 10: 98-102.
Shukair SA, Allen SA, Cianci GC, Stieh DJ, Anderson MR, Baig SM, et al. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement. Mucosal Immunol 2013; 6: 427-34.
Woodrow KA, Bennett KM, Lo DD. Mucosal vaccine design and delivery. Annu Rev Biomed Eng 2012; 14: 17-46.
Wira CR, Patel MV, Ghosh M, Mukura L, Fahey JV. Innate immunity in the human female reproductive tract: Endocrine regulation of endogenous antimicrobial protection against HIV and other sexually transmitted infections. Am J Reprod Immunol 2011; 65: 196-211.
Dezzutti CS, Brown ER, Moncla B, Russo J, Cost M, Wang L, et al. Is wetter better? An evaluation of over-the- counter personal lubricants for safety and anti-HIV-1 activity. PLoS One 2012; 7e48328
Kumamoto Y, Iwasaki A. Unique features of antiviral immune system of the vaginal mucosa. Curr Opin Immunol 2012; 24: 411-6.
Cherpes TL, Morrazzo JM, Cosentino LA, Meyn LA, Murray PJ, Hillier SL. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect 2008; 84: 57-61.
Verstraelen H, Swidsinski A. The biofilm in bacterial vaginosis: Implications for epidemiology, diagnosis and treatment. Curr Opin Infect Dis 2013; 26: 86-9.
Wira CR, Fahey JV, Ghosh M, Patel MV, Hickey DK, Ochiel DO. Sex hormone regulation of innate immunity in the female reproductive tract: The role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 2010; 63: 544-65.
Boskey ER, Telsch KM, Whaley KJ, Moench TR, Cone RA. Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification. Infect Immun 1999; 67: 5170-5.
da Neves J, Amilji M, Sarmento B. Mucoadhesive nanosystems for vaginal microbicide development friend or foe. WIRE Nanomed Nanobiotechnol 2011; 3: 389-99.
Chopra S, Motwani SK, Iqbal Z, Talegaonkar S, Ahmad FJ, Khar RK. Optimisation of polyherbal gels for vaginal drug delivery by Box-Behnken statistical design. Eur J Pharm Biopharm 2007; 67: 120-31.
Singh S, Verma D, Mirza MA, Das AK, Anwer MK, Sultana Y, et al. Development and optimization of ketoconazole loaded nano-transfersomal gel for vaginal delivery using Box-Behnken design: In vitro, ex vivo characterization and antimicrobial evaluation. J Drug Deliv Sci Technol 2017; 39: 95-103.
Mirza MA, Ahmad S, Mallick MN, Manzoor N, Talegaonkar S, Iqbal Z. Development of a novel synergistic thermosensitive gel for vaginal candidiasis: An in vitro, in vivo evaluation. Colloids Surf B Biointerfaces 2013; 103: 275-82.
Davey DA, Dommisse J. The management of hypertension in pregnancy. S Afr Med J 1980; 58: 551-6.
Hanson JM, McGregor JA, Hillier SL, Eschenbach DA, Kreutner AK, Galask RP, et al. Metronidazole for bacterial vaginosis: A comparison of vaginal gel vs. oral therapy. J Reprod Med 2000; 45: 889-96.
Levine H, Watson N. Comparison of the pharmacokinetics of Crinone 8% administered vaginally versus Prometrium administered orally in postmenopausal women. Fertil Steril 2000; 73: 516-21.
Chang JY, Oh YK, Kong HS, Kim EJ, Jang DD, Nam KT, et al. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J Control Release 2002; 82: 39-50.
Haineault C, Gourde P, Perron S, Désormeaux A, Piret A, Omar RF, et al. Thermoreversible gel formulation containing sodium lauryl sulfate as a potential contraceptive device. Biol Reprod 2003; 69: 687-94.
Bachhav YG, Patravale VB. Microemulsion based vaginal gel of fluconazole: Formulation, in vitro and in vivo evaluation. Int J Pharm 2009; 365: 175-9.
Forbes CJ, Mc Coy CF, Murphy DJ, Woolfson AD, Moore JP, Evans A, et al. Modified silicone elastomer vaginal gels for sustained release of antiretroviral HIV microbicides. J Pharm Sci 2014; 103: 1422-32.
Rençber S, Karavana SY, Şenyiğit ZY, Eraç B, Limoncu MH, Baloğlu EE. Mucoadhesive in situ gel formulation for vaginal delivery of clotrimazole: Formulation, preparation, and in vitro/in vivo evaluation. Pharm Dev Technol 2017; 22: 551-61.
Tuğcu-Demiröz F, Acartürk F, Özkul A. Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery. J Biomater Sci Polym 2015; 26: 1237-55.
Chen Y. TRaore YL, Li A, Fowke KR, Ho EA. Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine. Drug Des Devel Ther 2014; 8: 1801-15.
Traore YL, Chen Y, Bernier AM, Ho EA. Impact of hydroxychloroquine-loaded polyurethane intravaginal rings on lactobacilli. Antimicrob Agents Chemother 2015; 59: 7680-6.
Gunawardana M, Mullen MM, Yoo J, Webster P, Moss JA, Baum MM. Sustained delivery of commensal bacteria from pod-intravaginal rings. Antimicrob Agents Chemother 2014; 58: 2262-7.
Duan X, Ning M. Development and in vitro/in vivo evaluation of a silastic intravaginal ring for mifepristone delivery. Indian J Pharm Sci 2015; 77: 335-42.
Helbling IM, Ibarra JC, Luna JA. The optimization of an intravaginal ring releasing progesterone using a mathematical model. Pharm Res 2014; 31: 795-808.
Malcolm RK, Forbes CJ, Geer L, Veazey RS, Goldman L, Klasse PJ, et al. Pharmacokinetics and efficacy of a vaginally administered maraviroc gel in rhesus macaques. J Antimicrob Chemother 2013; 68(3): 678-83.
Hani U, Shivakumar HG, Anjum H, Pasha MY. Preparation and optimization of curcumin-hydroxy propyl cyclodextrin bioadhesive vaginal films for human papilloma virus-induced cervical cancer. J Biomater Tissue Eng 2014; 4: 796-803.
Dobaria NB, Badhan AC, Mashru RC. A novel itraconazole bioadhesive film for vaginal delivery: Design, optimization, and physicodynamic characterization. AAPS PharmSciTech 2009; 10: 951-9.
Akil A, Agashe H, Dezzutti CS, Moncla BJ, Hillier SL, Devlin B, et al. Formulation and characterization of polymeric films containing combinations of antiretrovirals (ARVs) for HIV prevention. Pharm Res 2015; 32: 458-68.
Mirza MA, Panda AK, Asif S, Verma D, Talegaonkar S, Manzoor N, et al. A vaginal drug delivery model. Drug Deliv 2016; 23: 3123-34.
Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review. J Control Release 2000; 65: 271-84.
Lai SK, O’Hanlon DE, Harrold S, Man ST, Wang YY, Cone R, et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc Natl Acad Sci USA 2007; 104: 1482-7.
Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci USA 2009; 106: 19268-73.
Mert O, Lai SK, Ensign L, Yang M, Wang YY, Wood J, et al. A poly(ethylene glycol)-based surfactant for formulation of drug-loaded mucus penetrating particles. J Control Release 2012; 157: 455-60.
Cu Y, Booth CJ, Saltzman WM. In vivo distribution of surface-modified PLGA nanoparticles following intravaginal delivery. J Control Release 2011; 156: 258-64.
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.
Wu Y, Navarro F, Lal A, Basar E, Pandey RK, Manoharan M, et al. Durable protection from herpes simplex virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene. Cell Host Microbe 2009; 5: 84-94.
Ariza-Sáenz M, Espina M, Bolaños N, Calpena AC, Gomara MJ, Haro I, et al. Penetration of polymeric nanoparticles loaded with an HIV-1 inhibitor peptide derived from GB virus C in a vaginal mucosa model. Eur J Pharm Biopharm 2017; 120: 98-106.
Zhang T, Sturgis TF, Youan BB. pH-responsive nanoparticles releasing tenofovir intended for the prevention of HIV transmission. Eur J Pharm Biopharm 2011; 79: 526-36.
Ham AS, Cost MR, Sassi AB, Dezzutti CS, Rohan LC. Targeted delivery of PSC-RANTES for HIV-1 prevention using biodegradable nanoparticles. Pharm Res 2009; 26: 502-11.
Neves J, Michiels J, Ariën KK, Vanham G, Amiji M, Bahia MF, et al. Polymeric nanoparticles affect the intracellular delivery, antiretroviral activity and cytotoxicity of the microbicide drug candidate dapivirine. Pharm Res 2012; 29: 1468-84.
Date AA, Shibata A, Goede M, et al. Development and evaluation of a thermosensitive vaginal gel containing raltegravir + efavirenz loaded nanoparticles for HIV prophylaxis. Antiviral Res 2012; 96: 430-6.
Martínez-Pérez B, Quintanar-Guerrero D, Tapia-Tapia M, Cisneros-Tamayo R, Zambrano-Zaragoza ML, Alcalá-Alcalá S, et al. Controlled-release biodegradable nanoparticles: From preparation to vaginal applications. Eur J Pharm Sci 2018; 115: 185-95.
Gu J, Yang S, Ho EA. Biodegradable film for the targeted delivery of sirna-loaded nanoparticles to vaginal immune cells. Mol Pharm 2015; 12: 2889-903.
Steinbach JM, Booth CJ, Saltzman WM. Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection. J Control Release 2012; 162: 102-10.
Looker KJ, Ronn MM, Brock PM, Brisson M, Drolet M, Mayaud P, et al. Evidence of synergistic relationships between HIV and Human Papillomavirus (HPV): Systematic reviews and meta‐analyses of longitudinal studies of HPV acquisition and clearance by HIV status, and of HIV acquisition by HPV status. J Int AIDS Soc 2018; 21e25110
Chiang G, Sassaroli M, Louie M, Chen H, Stecher VJ, Sperber K. Inhibition of HIV-1 replication by hydroxychloroquine. Clin Ther 1996; 18: 1080-92.
Barouch DH, Deeks SG. Immunologic strategies for HIV-1 remission and eradication. Science 2014; 345: 169-74.
Paton NI, Goodall RL, Dunn DT, Franzen S, Collaco-Moraes Y, Gazzard BG, et al. Effects of hydroxychloroquine on immune activation and disease progression among hiv-infected patients not receiving antiretroviral therapy a randomized controlled trial. JAMA 2012; 308: 353-61.
A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc (VHM) in Controlling HIV After Treatment, In: Bethesda (MD): National Library of Medicine (US). NLM Identifier: NCT02475915, 2015.
Wang L, Sassi AB, Patton D, Isaacs C, Moncla BJ, Gupta P, et al. Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention. Drug Dev Ind Pharm 2012; 38: 995-1007.
Maher S, Mc Clean S. Melittin exhibits necrotic cytotoxicity in gastrointestinal cells which is attenuated by cholesterol. Biochem Pharmacol 2008; 75: 1104-14.
Alukda D, Sturgis T, Youan BB. Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention. J Pharm Sci 2011; 100: 3345-56.
Patel DB, Patel JK. Liposomal drug delivery of metronidazole for the local treatment of vaginitis. Int J Pharm Sci Nanotechnol 2009; 2: 421-7.
Basnet P, Hussain H, Tho I, Skalko-Basnet N. Liposomal delivery systemenhances anti-inflammatory properties of curcumin. J Pharm Sci 2012; 101: 598-609.
Karimunnisa S, Atmaram P. Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal. Drug Dev Ind Pharm 2013; 39: 1328-37.
Berginc K, Suljaković S, Škalk BN, Kristl A. Mucoadhesive liposomes as new formulation for vaginal delivery of curcumin. Eur J Pharm Biopharm 2014; 87: 40-6.
Jøraholmen MW, Basnet P, Acharya G, Škalko-Basnet N. PEGylated liposomes for topical vaginal therapy improve delivery of interferon alpha. Eur J Pharm Biopharm 2017; 113: 132-9.
Frank LA, Chaves PS, D’Amore CM, Contri RV, Frank AG, Beck RC, et al. The use of chitosan as cationic coating or gel vehicle for polymeric nanocapsules: Increasing penetration and adhesion of imiquimod in vaginal tissue. Eur J Pharm Biopharm 2017; 114: 202-12.
Foldvari M, Badea I, Kumar P, Wettig S, Batta R, King MJ, et al. Biphasic vesicles for topical delivery of interferon alpha in human volunteers and treatment of patients with human papillomavirus infections. Curr Drug Deliv 2011; 8: 307-19.
Menjoge AR, Kannan RM, Tomalia DA. Dendrimer-based drug and imaging conjugates: Design considerations for nanomedical applications. Drug Discov Today 2010; 15: 171-85.
du Toit LC, Pillay V, Choonara YE. Nano-microbicides: Challenges in drug delivery, patient ethics and intellectual property in the war against HIV/AIDS. Adv Drug Deliv Rev 2010; 62: 532-46.
Nandy B, Saurabh S, Sahoo AK, Dixit NM, Maiti PK. The SPL7013 dendrimer destabilizes the HIV-1 gp120-CD4 complex. Nanoscale 2015; 7: 18628-41.
Rupp R, Rosenthal SL, Stanberry LR. VivaGel™ (SPL7013 Gel): A candidate dendrimer- microbicide for the prevention of HIV and HSV infection. Int J Nanomedicine 2007; 2: 561-6.
[79] "EU Marketing Approval Granted for VivaGel® BV."
Kensinger RD, Yowler BC, Benesi AJ, Schengrund CL. Synthesis of novel, multivalent glycodendrimers as ligands for HIV-1gp120. Bioconjug Chem 2004; 15: 349-58.
Rojo J, Delgado R. Glycodendritic structures: Promising new antiviral drugs. J Antimicrob Chemother 2004; 54: 579-81.
Dutta T, Garg M, Jain NK. Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur J Pharm Sci 2008; 34: 181-90.
Ganda IS, Zhong O, Hali M, Albuquerque RLC, Padilha FF, da Rocha SRP, et al. Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection. Int J Pharm 2017; 527: 79-91.
Wang B, Navath RS, Menjoge AR, Balakrishnan B, Bellair R, Dai H, et al. Inhibition of Bacterial Growth and Intramniotic Infection in a Guinea Pig Model of Chorioamnionitis Using PAMAM Dendrimers. Int J Pharm 2010; 395: 298-308.
Liu YT, Hussein WM, Jia Z, Ziora ZM, McMillan NAJ, Monteiro MJ, et al. Self-adjuvanting polymer–peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromol 2013; 14: 2798-806.
Kaur A, Saxena Y, Bansal R, Gupta S, Tyagi A, Sharma RK, et al. Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel. AAPS PharmSciTech 2017; 18: 2188-202.
Kassem AA, Marzouk MA, Ammar AA, Elosaily GH. Preparation and in vitro evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) containing clotrimazole. Drug Discov Ther 2010; 4: 373-9.
Aggarwal U, Goel AK, Rath G. Development and characterization of the cisplatin loaded nanofibers for the treatment of cervical cancer. Mater Sci Eng C Mater Biol Appl 2017; 75: 125-32.
Zong S, Wang X, Yang Y, Wu W, Li H, Ma Y, et al. The use of cisplatin-loaded mucoadhesive nanofibers for local chemotherapy of cervical cancers in mice. Eur J Pharm Biopharm 2015; 93: 127-35.
Kaur R, Garg T, Goyal AK, Rath G. Development, optimization and evaluation of electrospun nanofibers: Tool for targeted vaginal delivery of antimicrobials against urinary tract infections. Curr Drug Deliv 2016; 13: 754-63.
Agrahari V, Meng J, Ezoulin MJ, Youm I, Dim DC, Molteni A, et al. Stimuli-sensitive thiolated hyaluronic acid based nanofibers: Synthesis, preclinical safety and in vitro anti-HIV activity. Nanomedicine 2016; 11: 2935-58.
Jeyaraj M, Rajesh M, Arun R, Mubarak DA, Sathishkumar G, Sivanandhan G, et al. An investigation on the cytotoxicity and caspase-mediated apoptotic effect of biologically synthesized silver nanoparticles using podophyllum hexandrum on human cervical carcinoma cells. Colloids Surf B 2013; 102: 708-17.
Vasanth K, Ilango K, Mohan KR, Agrawal A, Dubey GP. Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction. Colloids Surf B 2014; 117: 354-9.
Rajasekharreddy P, Rani PU. Biofabrication of Ag nanoparticles using Sterculia foetida l., Seed extract and their toxic potential against mosquito vectors and HeLa cancer cells. Mater Sci Eng 2014; 39: 203-12.
Ghosh P, Han G, De M, Kim CK, Rotello VM. Gold nanoparticles in delivery applications. Adv Drug Deliv Rev 2008; 60: 1307-15.
Tomoaia G, Horovitz O, Mocanu A, Nita A, Avram A, Racz CP, et al. Effects of doxorubicin mediated by gold nanoparticles and resveratrol in two human cervical tumor cell lines. Colloids Surf B 2015; 135: 726-34.
Daduang J, Palasap P, Daduang S, Boonsiri P, Suwannalert P, Limpaiboon T. Gallic acid enhancement of gold nanoparticle anticancer activity in cervical cancer cells. Asian Pac J Cancer Prev 2015; 16: 169-74.
Ye L, Song Q. Promising potency of retinoic acid-poly(ethylene glycol)-thiol gold nanoparticle conjugates for cervical cancer treatment. Int J Clin Exp Med 2015; 8: 10501-7.
Martínez-Torres AC, Lorenzo-Anota HY, Ávila-Ávila A, Rodríguez-Abrego C, Rodríguez-Padilla C. Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production. Int J Nanomedicine 2018; 31: 3235-50.
Govindaraju S, Rengaraj A, Arivazhagan R, Huh YS, Yun KK. Curcumin-conjugated gold clusters for bioimaging and anticancer applications. Bioconjug Chem 2018; 29: 363-70.
Lin J, Hu W, Gao F, Qin J, Peng C, Lu X. Folic acid-modified diatrizoic acid-linked dendrimer-entrapped gold nanoparticles enable targeted CT imaging of human cervical cancer. J Cancer 2018; 9: 564-77.
Singh H, Du J, Singh P, Yi TH. Ecofriendly synthesis of silver and gold nanoparticles by Euphrasia officinalis leaf extract and its biomedical applications. Artif Cells Nanomed Biotechnol 2018; 46: 1163-70.
Hauser AK, Widra RJ, Stocke NA, Anderson KW, Hilt JZ. Magnetic nanoparticles and nanocomposites for remote controlled therapies. J Control Release 2015; 219: 76-94.
Song J, Hu Q, Huang J, Chen T, Ma Z, Shi H. MR targeted imaging for the expression of tenascin-C in cervical cancer. Br J Radiol 2018; 9120170681
Fakhimikabir H, Tavakoli MB, Zarrabi A, Amouheidari A, Rahgozar S. The role of folic acid-conjugated polyglycerol coated iron oxide nanoparticles on radiosensitivity with clinical electron beam (6 MeV) on human cervical carcinoma cell line: In vitro study. Photochem Photobiol B 2018; 182: 71-6.
Kim H, Jo A, Baek S, Lim D, Park SY, Cho SK, et al. Synergistically enhanced selective intracellular uptake of anticancer drug carrier comprising folic acid-conjugated hydrogels containing magnetite nanoparticles. Sci Rep 2017; 7: 41090.
Liu M, Wang Z, Zong S, Chen H, Zhu D, Zhong Y, et al. Remote-Controlled DNA release from Fe3O4@Au nanoparticles using an alternating electromagnetic field. J Biomed Nanotechnol 2015; 1: 979-87.
Russell WMS, Burch RL. The principles of humane experimental technique. London, UK: Methuen 1959.
Festing S, Wilkinson R. Science and society talking points the ethics of animal research. Talking point on the use of animals in scientific research. EMBO Rep 2007; 8: 526-30.
Woodrow KA, Ball C, Blakney A, Krogstad E, Nie H. Vaginal matrices: Nanofibers for contraception and prevention of HIV infection. US9393216B2 (2016).
Dov T, Besonov A, Meir E, Jorge D. Foam prepared from nanoemulsions and uses. US20170231909 (2017).
Lee R, Shenoy D, Wright D. Nanostructured composition and methods of making and using the same. US20070264349A1 (2007).
Singh KK, Tatke PA, Dhuru S. Neem oil contraceptive formulations. WO2006082596A3 (2007).
Min X, Yan Z, Yifei W, Xiaodan L, Zhengnan F, Yi W. Nano-silver chitosan gel foam preparation for treating vaginal bacterial inflammation, and preparation method thereof. CN102872159A (2013).
Hu C. Nano silver antiseptic gel for treating women's genital tract infection and its prepn and application. CN1672689A (2005).
Xue K, Xiaoyan B, Yue W, Huiru L. Thermo-sensitive type amphotericin B nano gel foam agent for vaginal administration. CN105616353 (2016).
Minzhong Y. Composition for antisepsis and anti-inflammation of vagina mucosas and preparation method of composition. CN106421575 (2017).

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [3 - 15]
Pages: 13
DOI: 10.2174/1872211313666190215141507

Article Metrics

PDF: 30