Generic placeholder image

Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Recent Advances in Vaginal Delivery for the Treatment of Vulvovaginal Candidiasis

Author(s): Sandeep Kaur and Sukhbir Kaur*

Volume 14 , Issue 3 , 2021

Published on: 21 June, 2020

Page: [281 - 291] Pages: 11

DOI: 10.2174/1573405616666200621200047

Price: $65


Background: Vulvovaginal candidiasis (VVC) is a common vaginal infection caused by candida species, affecting 70% of the women. It may occur due to the imbalance in the vaginal micro- biodata, pregnancy, diabetes, use of antibiotics, frequent sexual activities or AIDS.

Aim: The main aim of this review is to provide overview about different vaginal delivery systems for the administration of antifungal agents like conventional, mucoadhesive and muco-penetrating delivery systems.

Method: The conventional delivery systems available have limited efficacy due to the less residence time and adverse effects. In order to overcome these issues, a delivery system with mucoadhesive and muco-penetrating properties is required. Mucoadhesive polymers have excellent binding properties with mucin and thus increasing residence time. On the other hand, muco-penetrating polymers transport the antifungal agents across the mucus layer.

Results: This review summarizes the pathophysiology of VVC along with novel delivery systems for the treatment of infection through mucoadhesive and muco-penetrating approaches. Surface modifications of nano/ microparticles with mucoadhesive or muco-penetrating particles may provide delivery systems with improved therapeutic efficacy.

Conclusion: Based on the available data, conventional and mucoadhesive drug delivery systems have some limitations, they still require improvement/ development for safe and effective delivery of antifungal agents.

Keywords: Valvovaginal candidiasis, conventional delivery system, mucoadhesion, mucopenetration, novel delivery systems, Candida albican.

Graphical Abstract
Dobaria, N.; Mashru, R.; Vadia, N.H. Vaginal drug delivery systems: A review of current status. East Cent. Afr. J. Pharm. Sci., 2007, 10(1), 3-13.
Choudhury, A.; Das, S.; Kar, M. A review on novelty and potentiality of vaginal drug delivery. Int. J. Pharm. Tech. Res., 2011, 3, 1033-1044.
Pavelić, Z.; Škalko-Basnet, N.; Schubert, R. Liposomal gels for vaginal drug delivery. Int. J. Pharm., 2001, 219(1-2), 139-149.
[] [PMID: 11337174]
Keshwani, B.; Sharma, D.; Chatterjee, A.; Jamini, M.; Arora, P. Novel Concepts in Vaginal Drug Delivery. J. Pharma Res., 2014, 3(10), 184-187.
Mulu, W; Yimer, M; Zenebe, Y; Abera, B Common causes of vaginal infections and antibiotic susceptibility of aerobic bacterial isolates in women of reproductive age attending at Felegehiwot referral Hospital, Ethiopia: a cross sectional study. BMC women's health., 2015, 15(1), 42.
Haltas, H.; Bayrak, R.; Yenidunya, S. To determine of the prevalence of Bacterial Vaginosis, Candida sp, mixed infections (Bacterial Vaginosis + Candida sp), Trichomonas Vaginalis, Actinomyces sp in Turkish women from Ankara, Turkey. Ginekol. Pol., 2012, 83(10), 744-748.
[PMID: 23383559]
Berry, M. Vaginal infections: an overview. Pharm. Pract. (Granada), 2005, 21(9), S1-S8.
das Neves, J.; Pinto, E.; Teixeira, B.; Dias, G.; Rocha, P.; Cunha, T.; Santos, B.; Amaral, M.H.; Bahia, M.F. Local treatment of vulvovaginal candidosis : general and practical considerations. Drugs, 2008, 68(13), 1787-1802.
[] [PMID: 18729533]
Moreno-Ruiz, E.; Galán-Díez, M.; Zhu, W.; Fernández-Ruiz, E.; d’Enfert, C.; Filler, S.G.; Cossart, P.; Veiga, E. Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell. Microbiol., 2009, 11(8), 1179-1189.
[] [PMID: 19416270]
Naglik, J.R.; Moyes, D.L.; Wächtler, B.; Hube, B. Candida albicans interactions with epithelial cells and mucosal immunity. Microbes Infect., 2011, 13(12-13), 963-976.
[] [PMID: 21801848]
Moyes, D.L.; Richardson, J.P.; Naglik, J.R. Candida albicans-epithelial interactions and pathogenicity mechanisms: scratching the surface. Virulence, 2015, 6(4), 338-346.
[] [PMID: 25714110]
Loza, L.; Fu, Y.; Ibrahim, A.S.; Sheppard, D.C.; Filler, S.G.; Edwards, J.E., Jr Functional analysis of the Candida albicans ALS1 gene product. Yeast, 2004, 21(6), 473-482.
[] [PMID: 15116430]
Rauceo, J.M.; De Armond, R.; Otoo, H.; Kahn, P.C.; Klotz, S.A.; Gaur, N.K.; Lipke, P.N. Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryot. Cell, 2006, 5(10), 1664-1673.
[] [PMID: 16936142]
Hoyer, L.L.; Green, C.B.; Oh, S.H.; Zhao, X. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit. Med. Mycol., 2008, 46(1), 1-15.
[] [PMID: 17852717]
Liu, Y.; Filler, S.G. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot. Cell, 2011, 10(2), 168-173.
[] [PMID: 21115738]
Phan, Q.T.; Fratti, R.A.; Prasadarao, N.V.; Edwards, J.E., Jr; Filler, S.G. N-cadherin mediates endocytosis of Candida albicans by endothelial cells. J. Biol. Chem., 2005, 280(11), 10455-10461.
[] [PMID: 15632157]
Johal, H.S.; Garg, T.; Rath, G.; Goyal, A.K. Advanced topical drug delivery system for the management of vaginal candidiasis. Drug Deliv., 2016, 23(2), 550-563.
[] [PMID: 24959937]
Spreghini, E.; Gismondi, A.; Piccoli, M.; Santoni, G. Evidence for alphavbeta3 and alphavbeta5 integrin-like vitronectin (VN) receptors in Candida albicans and their involvement in yeast cell adhesion to VN. J. Infect. Dis., 1999, 180(1), 156-166.
[] [PMID: 10353874]
Diamond, G.; Beckloff, N.; Ryan, L.K. Host defense peptides in the oral cavity and the lung: similarities and differences. J. Dent. Res., 2008, 87(10), 915-927.
[] [PMID: 18809744]
Moyes, D.L.; Runglall, M.; Murciano, C.; Shen, C.; Nayar, D.; Thavaraj, S.; Kohli, A.; Islam, A.; Mora-Montes, H.; Challacombe, S.J.; Naglik, J.R. A biphasic innate immune MAPK response discriminates between the yeast and hyphal forms of Candida albicans in epithelial cells. Cell Host Microbe, 2010, 8(3), 225-235.
[] [PMID: 20833374]
Moyes, D.L.; Murciano, C.; Runglall, M.; Kohli, A.; Islam, A.; Naglik, J.R. Activation of MAPK/c-Fos induced responses in oral epithelial cells is specific to Candida albicans and Candida dubliniensis hyphae. Med. Microbiol. Immunol. (Berl.), 2012, 201(1), 93-101.
[] [PMID: 21706283]
Sun, J.N.; Solis, N.V.; Phan, Q.T.; Bajwa, J.S.; Kashleva, H.; Thompson, A.; Liu, Y.; Dongari-Bagtzoglou, A.; Edgerton, M.; Filler, S.G. Host cell invasion and virulence mediated by Candida albicans Ssa1. PLoS Pathog., 2010, 6(11)e1001181
[] [PMID: 21085601]
Wächtler, B.; Wilson, D.; Haedicke, K.; Dalle, F.; Hube, B. From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells. PLoS One, 2011, 6(2)e17046
[] [PMID: 21407800]
Sahoo, C.K.; Nayak, P.K.; Sarangi, D.K.; Sahoo, T.K. Intra vaginal drug delivery system: An overview. Am. J. Adv. Drug Deliv., 2013, 1, 43-55.
Chew, S.Y.; Than, L.T. Vulvovaginal candidosis: Contemporary challenges and the future of prophylactic and therapeutic approaches. Mycoses., 2016, 59(5), 262-273.
[] [PMID: 26765516]
Singh, H.; Sharma, R.; Joshi, M.; Garg, T.; Goyal, A.K.; Rath, G. Transmucosal delivery of Docetaxel by mucoadhesive polymeric nanofibers. Artif. Cells Nanomed. Biotechnol., 2015, 43(4), 263-269.
[] [PMID: 24621011]
das Neves, J.; Nunes, R.; Machado, A.; Sarmento, B. Polymer-based nanocarriers for vaginal drug delivery. Adv. Drug Deliv. Rev., 2015, 92, 53-70.
[] [PMID: 25550217]
Leyva-Gómez, G.; Piñón-Segundo, E.; Mendoza-Muñoz, N.; Zambrano-Zaragoza, M.L.; Mendoza-Elvira, S.; Quintanar-Guerrero, D. 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.
[] [PMID: 29882846]
Ensign, L.M.; Tang, B.C.; Wang, Y.Y.; Tse, T.A.; Hoen, T.; Cone, R.; Hanes, J. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci. Transl. Med., 2012, 4(138)138ra79
[] [PMID: 22700955]
das Neves, J.; Amiji, M.; Sarmento, B. Mucoadhesive nanosystems for vaginal microbicide development: friend or foe? Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol., 2011, 3(4), 389-399.
[] [PMID: 21506290]
Fröhlich, E.; Roblegg, E. Mucus as barrier for drug delivery by nanoparticles. J. Nanosci. Nanotechnol., 2014, 14(1), 126-136.
[] [PMID: 24730255]
Wong, T.W.; Dhanawat, M.; Rathbone, M.J. Vaginal drug delivery: strategies and concerns in polymeric nanoparticle development. Expert Opin. Drug Deliv., 2014, 11(9), 1419-1434.
[] [PMID: 24960192]
Zhang, H.; Shahbazi, M.A.; Almeida, P.V.; Santos, H.A. Mucus as a barrier for biopharmaceuticals and drug delivery systems.Mucosal Delivery of Biopharmaceuticals; , 2014, pp. 59-97..
Lai, S.K.; Wang, Y.Y.; Hanes, J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug Deliv. Rev., 2009, 61(2), 158-171.
[] [PMID: 19133304]
Kieweg, S.L.; Katz, D.F. Squeezing flows of vaginal gel formulations relevant to microbicide drug delivery. J. Biomech. Eng., 2006, 128(4), 540-553.
[] [PMID: 16813445]
de Araújo Pereira, R.R.; Bruschi, M.L. Vaginal mucoadhesive drug delivery systems. Drug Dev. Ind. Pharm., 2012, 38(6), 643-652.
[] [PMID: 21999572]
Hussain, A.; Ahsan, F. The vagina as a route for systemic drug delivery. J. Control. Release, 2005, 103(2), 301-313.
[] [PMID: 15763615]
Valenta, C. The use of mucoadhesive polymers in vaginal delivery. Adv. Drug Deliv. Rev., 2005, 57(11), 1692-1712.
[] [PMID: 16182407]
Andrews, G.P.; Laverty, T.P.; Jones, D.S. Mucoadhesive polymeric platforms for controlled drug delivery. Eur. J. Pharm. Biopharm., 2009, 71(3), 505-518.
[] [PMID: 18984051]
Jones, D.S.; Bruschi, M.L.; de Freitas, O.; Gremião, M.P.; Lara, E.H.; Andrews, G.P. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int. J Pharm., 2009, 372(1-2), 49-58.
Rowe, R.C.; Sheskey, P.J.; Owen, S.C. Handbook of pharmaceutical excipients; Pharmaceutical press: London, 2006.
Acartürk, F. Mucoadhesive vaginal drug delivery systems. Recent Pat. Drug Deliv. Formul., 2009, 3(3), 193-205.
[] [PMID: 19925443]
Bernkop-Schnürch, A.; Egger, C.; Elhassan Imam, M.; Krauland, A.H. Preparation and in vitro characterization of poly(acrylic acid)-cysteine microparticles. J. Control. Release, 2003, 93(1), 29-38.
[] [PMID: 14602419]
Cho, W.J.; Oh, S.H.; Lee, J.H. Alginate film as a novel post-surgical tissue adhesion barrier. J. Biomater. Sci. Polym. Ed., 2010, 21(6-7), 701-713.
[] [PMID: 20482979]
Pawar, S.N.; Edgar, K.J. Alginate derivatization: a review of chemistry, properties and applications. Biomaterials, 2012, 33(11), 3279-3305.
[] [PMID: 22281421]
Netsomboon, K.; Bernkop-Schnürch, A. Mucoadhesive vs. mucopenetrating particulate drug delivery. Eur. J. Pharm. Biopharm., 2016, 98, 76-89.
[] [PMID: 26598207]
Vanić, Ž.; Hurler, J.; Ferderber, K.; Golja Gašparović, P.; Škalko-Basnet, N.; Filipović-Grčić, J. Novel vaginal drug delivery system: deformable propylene glycol liposomes-in-hydrogel. J. Liposome Res., 2014, 24(1), 27-36.
[] [PMID: 23931627]
Grabovac, V.; Guggi, D.; Bernkop-Schnürch, A. Comparison of the mucoadhesive properties of various polymers. Adv. Drug Deliv. Rev., 2005, 57(11), 1713-1723.
[] [PMID: 16183163]
Sigurdsson, H.H.; Loftsson, T.; Lehr, C.M. Assessment of mucoadhesion by a resonant mirror biosensor. Int. J. Pharm., 2006, 325(1-2), 75-81.
[] [PMID: 16904852]
Rahmat, D.; Müller, C.; Barthelmes, J.; Shahnaz, G.; Martien, R.; Bernkop-Schnürch, A. Thiolated hydroxyethyl cellulose: design and in vitro evaluation of mucoadhesive and permeation enhancing nanoparticles. Eur. J. Pharm. Biopharm., 2013, 83(2), 149-155.
[] [PMID: 23148989]
Sosnik, A. das Neves J, Sarmento B. Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: a review. Prog. Polym. Sci., 2014, 39(12), 2030-2075.
Sundar Raj, A.A.; Rubila, S.; Jayabalan, R.; Ranganathan, T.V. A review on pectin: Chemistry due to general properties of pectin and its pharmaceutical uses. Sci. Rep., 2012, 1, 550-551.
Sogias, I.A.; Williams, A.C.; Khutoryanskiy, V.V. Why is chitosan mucoadhesive? Biomacromolecules, 2008, 9(7), 1837-1842.
[] [PMID: 18540644]
Pillai, C.K.; Paul, W.; Sharma, C.P. Chitin and chitosan polymers: Chemistry, solubility and fiber formation. Prog. Polym. Sci., 2009, 34(7), 641-678.
Iqbal, J.; Shahnaz, G.; Perera, G.; Hintzen, F.; Sarti, F.; Bernkop-Schnürch, A. Thiolated chitosan: development and in vivo evaluation of an oral delivery system for leuprolide. Eur. J. Pharm. Biopharm., 2012, 80(1), 95-102.
[] [PMID: 21964316]
Foldvari, M.; Badea, I.; Kumar, P.; Wettig, S.; Batta, R.; King, M.J.; He, Z.; Yeboah, E.; Gaspar, K.; Hull, P.; Shear, N.H. Biphasic vesicles for topical delivery of interferon alpha in human volunteers and treatment of patients with human papillomavirus infections. Curr. Drug Deliv., 2011, 8(3), 307-319.
[] [PMID: 21291377]
Vanić, Ž.; Škalko-Basnet, N. Nanopharmaceuticals for improved topical vaginal therapy: can they deliver? Eur. J. Pharm. Sci., 2013, 50(1), 29-41.
[] [PMID: 23684936]
Rahman, S.S.; Ahmed, A.B. Vaginal Drug Delivery System a Promising Approach for Antiretroviral Drug in the Prevention of HIV Infection: A Review. Journal of Pharmaceutical Sciences and Research., 2016, 8(12), 1330.
da Silva, P.B.; Ramos, M.A.; Bonifácio, B.V.; Negri, K.M.; Sato, M.R.; Bauab, T.M.; Chorilli, M.; Chorilli, M. Nanotechnological strategies for vaginal administration of drugs--a review. J. Biomed. Nanotechnol., 2014, 10(9), 2218-2243.
[] [PMID: 25992455]
Karasulu, H.Y.; Hilmioğlu, S.; Metin, D.Y.; Güneri, T. Efficacy of a new ketoconazole bioadhesive vaginal tablet on Candida albicans. Farmaco, 2004, 59(2), 163-167.
[] [PMID: 14871509]
Perioli, L; Ambrogi, V; Pagano, C; Scuota, S; Rossi, C. FG90 chitosan as a new polymer for metronidazole mucoadhesive tablets for vaginal administration. International journal of pharmaceutics., 2009, 377(1-2), 120-127.
Mauck, C.K.; Katz, D.; Sandefer, E.P.; Nasution, M.D.; Henderson, M.; Digenis, G.A.; Su, I.; Page, R.; Barnhart, K. Vaginal distribution of Replens and K-Y Jelly using three imaging techniques. Contraception, 2008, 77(3), 195-204.
[] [PMID: 18279691]
de Lima, J.A.; Paines, T.C.; Motta, M.H.; Weber, W.B.; Dos Santos, S.S.; Cruz, L.; da Silva, C.B. Novel Pemulen/Pullulan blended hydrogel containing clotrimazole-loaded cationic nanocapsules: Evaluation of mucoadhesion and vaginal permeation. Mater. Sci. Eng. C, 2017, 79, 886-893.
[] [PMID: 28629093]
Li, Y.; Zhao, H.; Duan, L.R.; Li, H.; Yang, Q.; Tu, H.H.; Cao, W.; Wang, S.W. Preparation, characterization and evaluation of bufalin liposomes coated with citrus pectin. Colloids Surf. A Physicochem. Eng. Asp., 2014, 444, 54-62.
Jøraholmen, M.W.; Basnet, P.; Acharya, G.; Škalko-Basnet, N. PEGylated liposomes for topical vaginal therapy improve delivery of interferon alpha. Eur. J. Pharm. Biopharm., 2017, 113, 132-139.
[] [PMID: 28087379]
Wang, J.; Huang, G. Preparation of itraconazole-loaded liposomes coated by carboxymethyl chitosan and its pharmacokinetics and tissue distribution. Drug Deliv., 2011, 18(8), 631-638.
[PMID: 22111976]
Marques, M.R.; Loebenberg, R.; Almukainzi, M. Simulated biological fluids with possible application in dissolution testing. Dissolut. Technol., 2011, 18(3), 15-28.
Das, R.K.; Kasoju, N.; Bora, U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine (Lond.), 2010, 6(1), 153-160.
[] [PMID: 19616123]
Kenechukwu, F.C.; Attama, A.A.; Ibezim, E.C.; Nnamani, P.O.; Umeyor, C.E.; Uronnachi, E.M.; Momoh, M.A.; Akpa, P.A.; Ozioko, A.C. Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. BioMed. Res. Int., 2018, 2018, 3714329.
Lucena, P.A.; Nascimento, T.L.; Gaeti, M.P.N.; de Ávila, R.I.; Mendes, L.P.; Vieira, M.S.; Fabrini, D.; Amaral, A.C.; Lima, E.M. In vivo Vaginal Fungal Load Reduction After Treatment with Itraconazole-Loaded Polycaprolactone-Nanoparticles. J. Biomed. Nanotechnol., 2018, 14(7), 1347-1358.
[] [PMID: 29944108]
Souza, R.O.; Henrique de Lima, T.; Oréfice, R.L.; de Freitas Araújo, M.G.; de Lima Moura, S.A.; Magalhães, J.T.; da Silva, G.R. Amphotericin B-Loaded Poly(lactic-co-glycolic acid) Nanofibers: An Alternative Therapy Scheme for Local Treatment of Vulvovaginal Candidiasis. J. Pharm. Sci., 2018, 107(10), 2674-2685.
[] [PMID: 29940181]
Santos, S.S.; Lorenzoni, A.; Pegoraro, N.S.; Denardi, L.B.; Alves, S.H.; Schaffazick, S.R.; Cruz, L. Formulation and in vitro evaluation of coconut oil-core cationic nanocapsules intended for vaginal delivery of clotrimazole. Colloids Surf. B Biointerfaces, 2014, 116, 270-276.
[] [PMID: 24503350]
Sharma, R.; Garg, T.; Goyal, A.K.; Rath, G. Development, optimization and evaluation of polymeric electrospun nanofiber: A tool for local delivery of fluconazole for management of vaginal candidiasis. Artif. Cells Nanomed. Biotechnol., 2016, 44(2), 524-531.
[] [PMID: 25315503]
Abruzzo, A.; Giordani, B.; Parolin, C.; Vitali, B.; Protti, M.; Mercolini, L.; Cappelletti, M.; Fedi, S.; Bigucci, F.; Cerchiara, T.; Luppi, B. Novel mixed vesicles containing lactobacilli biosurfactant for vaginal delivery of an anti-Candida agent. Eur. J. Pharm. Sci., 2018, 112, 95-101.
[] [PMID: 29138104]
Cevher, E.; Açma, A.; Sinani, G.; Aksu, B.; Zloh, M.; Mülazımoğlu, L. Bioadhesive tablets containing cyclodextrin complex of itraconazole for the treatment of vaginal candidiasis. Int. J. Biol. Macromol., 2014, 69, 124-136.
[] [PMID: 24857873]
Bassi, P.; Kaur, G. Bioadhesive vaginal drug delivery of nystatin using a derivatized polymer: Development and characterization. Eur. J. Pharm. Biopharm., 2015, 96, 173-184.
[] [PMID: 26235393]
Karimunnisa, S.; Atmaram, P. Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal. Drug Dev. Ind. Pharm., 2013, 39(9), 1328-1337.
[] [PMID: 22866766]
Parodi, B.; Russo, E.; Caviglioli, G.; Baldassari, S.; Gaglianone, N.; Schito, A.M.; Cafaggi, S. A chitosan lactate/poloxamer 407-based matrix containing Eudragit RS microparticles for vaginal delivery of econazole: design and in vitro evaluation. Drug Dev. Ind. Pharm., 2013, 39(12), 1911-1920.
[] [PMID: 22681543]
Martínez-Pérez, B.; Quintanar-Guerrero, D.; Tapia-Tapia, M.; Cisneros-Tamayo, R.; Zambrano-Zaragoza, M.L.; Alcalá-Alcalá, S.; Mendoza-Muñoz, N.; Piñón-Segundo, E. Controlled-release biodegradable nanoparticles: From preparation to vaginal applications. Eur. J. Pharm. Sci., 2018, 115, 185-195.
[] [PMID: 29208486]
Martín-Villena, M.J.; Fernández-Campos, F.; Calpena-Campmany, A.C.; Bozal-de Febrer, N.; Ruiz-Martínez, M.A.; Clares-Naveros, B. Novel microparticulate systems for the vaginal delivery of nystatin: Development and characterization. Carbohydr. Polym., 2013, 94(1), 1-11.
[] [PMID: 23544502]
Albertini, B.; Passerini, N.; Di Sabatino, M.; Vitali, B.; Brigidi, P.; Rodriguez, L. Polymer-lipid based mucoadhesive microspheres prepared by spray-congealing for the vaginal delivery of econazole nitrate. Eur. J. Pharm. Sci., 2009, 36(4-5), 591-601.
[] [PMID: 19150403]
Chang, J.Y.; Oh, Y.K.; Kong, H.S.; Kim, E.J.; Jang, D.D.; Nam, K.T.; Kim, C.K. Prolonged antifungal effects of clotrimazole-containing mucoadhesive thermosensitive gels on vaginitis. J. Control. Release, 2002, 82(1), 39-50.
[] [PMID: 12106975]
Kast, C.E.; Valenta, C.; Leopold, M.; Bernkop-Schnürch, A. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J. Control. Release, 2002, 81(3), 347-354.
[] [PMID: 12044573]
Ceschel, G.C.; Maffei, P.; Lombardi Borgia, S.; Ronchi, C.; Rossi, S. Development of a mucoadhesive dosage form for vaginal administration. Drug Dev. Ind. Pharm., 2001, 27(6), 541-547.
[] [PMID: 11548861]
Ameen, D.W. Development and in vitro evaluation of bioadhesive vaginal tablet using econazole nitrate as a model drug. Iraqi J. Pharm. Sci., 2011, 20(1), 57-65.
Sharma, G.; Jain, S.; Tiwary, A.K.; Kaur, G. Once daily bioadhesive vaginal clotrimazole tablets: design and evaluation. Acta Pharm., 2006, 56(3), 337-345.
[PMID: 19831282]
Wang, L; Tang, X. A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and ‘in vivo’ evaluation. Int. J. Pharm., 2008, 350(1-2), 181-187.
Bhat, S.; Shivakumar, H.G. Bioadhesive controlled release clotrimazole vaginal tablets. Trop. J. Pharm. Res., 2010, 9(4), 339-346.
Geeta, P.M.; Patel, A.P. A novel effervescent bioadhesive vaginal tablet of ketoconazole: formulation and in-vitro evaluation. Int. J. Pharm. Tech. Res., 2010, 2(1), 656-667.
Patel, A.; Patel, J.; Patel, J. Design, development and in vitro evaluation of sertaconazole mucoadhesive vaginal tablet. Der Pharmacia Lettre., 2012, 4(2), 418-427.
Dangi, A.A.; Sheth, N.R.; Patel, H.J. Formulation and evaluation of once daily mucoadhesive vaginal tablet of clotrimazole using natural and synthetic polymers. Asian J. Pharm. Health Sci., 2011, 1, 176-182.
Gupta, N.V.; Natasha, S.; Getyala, A.; Bhat, R.S. Bioadhesive vaginal tablets containing spray dried microspheres loaded with clotrimazole for treatment of vaginal candidiasis. Acta Pharm., 2013, 63(3), 359-372.
[] [PMID: 24152896]
Ahmad, F.J.; Alam, M.A.; Khan, Z.I.; Khar, R.K.; Ali, M. Development and in vitro evaluation of an acid buffering bioadhesive vaginal gel for mixed vaginal infections. Acta Pharm., 2008, 58(4), 407-419.
[] [PMID: 19103575]
Karavana, S.Y.; Rençbe, S.; Şenyiğit, Z.A.; Baloğlu, E. A new in-situ gel formulation of itraconazole for vaginal administration. Pharmacol. Pharm., 2012, 3(04), 417.
Hani, U; Shivakumar, HG Development of miconazole nitrate thermosensitive bioadhesivevaignal gel for vaginal candidiasis. Open J. Adv. Drug Deliv., 2013, 30. 1(3), 358-368.
Bilensoy, E.; Rouf, M.A.; Vural, I.; Šen, M.; Hincal, A.A. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:β-cyclodextrin complex. AAPS PharmSciTech, 2006, 7(2)E38
[] [PMID: 16796356]
Ning, M.; Guo, Y.; Pan, H.; Chen, X.; Gu, Z. Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev. Ind. Pharm., 2005, 31(4-5), 375-383.
[] [PMID: 16093203]
Kang, J.W.; Davaa, E.; Kim, Y.T.; Park, J.S. A new vaginal delivery system of amphotericin B: a dispersion of cationic liposomes in a thermosensitive gel. J. Drug Target., 2010, 18(8), 637-644.
[] [PMID: 20192816]
Carrillo-Muñoz, A.J.; Quindós, G.; Tur, C.; Ruesga, M.T.; Miranda, Y.; del Valle, O.; Cossum, P.A.; Wallace, T.L. In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole. J. Antimicrob. Chemother., 1999, 44(3), 397-401.
[] [PMID: 10511410]
Basnet, P.; Hussain, H.; Tho, I.; Skalko-Basnet, N. Liposomal delivery system enhances anti-inflammatory properties of curcumin. J. Pharm. Sci., 2012, 101(2), 598-609.
[] [PMID: 21989712]
Kaur, S.; Narang, R.K.; Aggarwal, G. Formulation and development of colon-targeted mucopenetrating metronidazole nanoparticles. Trop. J. Pharm. Res., 2017, 16(5), 967-973.
Rudzinski, W.E.; Palacios, A.; Ahmed, A.; Lane, M.A.; Aminabhavi, T.M. Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles. Carbohydr. Polym., 2016, 147, 323-332.
[] [PMID: 27178938]
Craparo, E.F.; Porsio, B.; Sardo, C.; Giammona, G.; Cavallaro, G. Pegylated polyaspartamide–polylactide-based nanoparticles penetrating cystic fibrosis artificial mucus. Biomacromolecules, 2016, 17(3), 767-777.
[] [PMID: 26866983]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy