Abstract
Background & Objectives: Fungi are the heterotrophic eukaryotic organisms which are useful as they causes the biodegradation. There are still some harmful species like yeasts, molds and dermatophytes which cause the infections. As the fungi are eukaryotics, they do not respond to the antibiotic therapy due to the limitations associated with the traditional antibiotic therapies. There are several antifungal agents introduced to treat such infections. These antifungal agents posses severe problems like drug resistance and toxicity due to the higher dose which comprises the need for newer alternatives over conventional dosage forms. Novel drug delivery systems proved to be a better approach to enhance the effectiveness of the antifungals and enhance patient compliance by reducing the adverse effect.
Discussion: This review focused on the general information about fungal infections, types and mechanism of action of antifungal agents and overview of formulation approaches such as vesicular system, colloidal system, nanoparticulate system and in situ gelling which are often studied for antifungal treatments.
Conclusion: We concluded that the novel drug delivery systems are the essential techniques for delivering the antifungal agents to their target site with desired concentration. Moreover, the researchers focused on these novel drug deliveries which mainly concentrate on controlling & sustaining the release of antifungal agents.
Keywords: Antifungal agents, fungi, NDDS, fungal infections, nanoparticulate system, in situ gels.
Graphical Abstract
[1]
Castelli, M.; Butassi, E.; Monteiro, M.; Svetaz, L.; Vicente, F.; Zacchino, S. Novel antifungal agents: A patent review. Expert Opin. Drug Deliv., 2014, 24(3), 323-338.
[2]
Willaer, R. Micro- and nanoscale approaches in antifungal drug discovery. Ferment. Technol., 2018, 4(2), 1-23.
[4]
Güngör, S.; Erdal, M.; Aksu, B. New formulation strategies in topical antifungal therapy. J. Cosmet. Dermatol., 2013, 3(1), 56-65.
[5]
Golan, D.; Armstrong, A.; Armstrong, E. Principles of pharmacology: The pathophysiologic basis of drug therapy, 4th ed; Wolters Kluwer: New-Delhi, India, 2017, pp. 662-663.
[6]
Kaur, I.; Kakkar, S. Topical delivery of antifungal agents. Expert Opin. Drug Deliv., 2010, 7(11), 1303-1327.
[8]
Bhowmik, B.; Aravind, S.; Gowda, D.; Singh, A.; Srivastava, A.; Osmani, R. Recent trends and advances in fungal drug delivery. J. Chem. Pharm. Res., 2016, 8(4), 169-178.
[9]
Magliani, W.; Conti, S.; Salati, A.; Arseni, S.; Frazzi, R.; Ravanetti, L.; Polonelli, L. New strategies for treatment of Candida vaginal infections. Rev. Iberoam. Micol., 2002, 19(3), 144-148.
[10]
Sawant, B.; Khan, T. Recent advances in delivery of antifungal agents for therapeutic management of candidiasis. Biomed. Pharmacother., 2017, 96, 1478-1490.
[11]
Souto, E.; Wissing, S.; Barbosa, C.; Müller, R. Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery. Int. J. Pharm., 2004, 278(1), 71-77.
[12]
Nakarani, M.; Misra, A.; Patel, J.; Vaghani, S. Itraconazole nanosuspension for oral delivery: Formulation, characterization and in vitro comparison with marketed formulation. Daru, 2010, 18(2), 84-90.
[13]
Lemke, A.; Kiderlen, A.; Kayser, O.; Amphotericin, B. Appl. Microbiol. Biotechnol., 2005, 68(2), 151-162.
[14]
Wasan, E.; Bartlett, K.; Gershkovich, P.; Sivak, P.; Banno, B.; Wong, Z.; Gagnon, J.; Gates, F.; Leon, C.; Wasan, K. Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans. Int. J. Pharm., 2009, 372(1-2), 76-84.
[15]
Radwan, M.; AlQuadeib, B.; Siller, L.; Wright, M.; Horrocks, B. Oral administration of amphotericin B nanoparticles: Antifungal activity, bioavailability and toxicity in rats. Drug Deliv., 2017, 24(1), 40-50.
[16]
Das, S.; Suresh, P.; Deshmukh, R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine , 2010, 6(2), 318-323.
[17]
Salernoa, C.; Chiappetta, D.; Arechavalac, A.; Gorzalczany, S.; Sciosciaa, S.; Bergni, C. Lipid-based microtubes for topical delivery of Amphotericin B. Colloids Surf. B Biointerfaces, 2013, 107, 160-166.
[18]
Butani, D.; Yewale, C.; Misra, A. Topical Amphotericin B solid lipid nanoparticles: Design and development. Colloids Surf. B Biointerfaces, 2016, 139, 17-24.
[19]
Jain, K.; Verma, A.; Mishra, P.; Jain, N. Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers. Nanomedicine , 2015, 11(3), 705-713.
[20]
Fu, T.; Yi, J.; Lv, S.; Zhang, B. Ocular amphotericin B delivery by chitosan modified nanostructured lipid carriers for fungal keratitis targeted therapy. J. Liposome Res., 2017, 27(3), 228-233.
[21]
Ling Tan, J.; Roberts,, c; Billa,, N Mucoadhesive chitosan-coated nanostructured lipid carriers for oral delivery of amphotericin B. Pharm. Dev. Technol., 2019, 24, 504-512.
[22]
Lidwiq, D.; de Camargo, A.; Khalil, M.; Auler, E.; Mainardes, M. Antifungal activity of chitosan-coated poly (lactic-co-glycolic) acid nanoparticle containing Amphotericin B. Mycopathologia, 2018, 183, 659-668.
[23]
Campos, F.; Campmany, A.; Delgado, G.; Serrano, O.; Naveros, B. Development and characterization of a novel nystatin-loaded nanoemulsion for the buccal treatment of candidosis: Ultrastructural effects and release studies. J. Pharm. Sci., 2012, 101(10), 3739-3752.
[24]
Semis, R.; Polacheck, I.; Segal, E. Nystatin-intralipid preparation: Characterization and in vitro activity against yeasts and molds. Mycopathologia, 2010, 169(5), 333-341.
[25]
El-Ridy, M.; Abdelbary, A.; Essam, T. EL-Salam, A.; Kassem, A. Niosomes as a potential drug delivery system for increasing the efficacy and safety of nystatin. Drug Dev. Ind. Pharm., 2011, 37(12), 1491-1508.
[26]
Campos, F.; Naveros, B.; Serrano, O.; Delgado, G.; Campmany, A. Development and characterization of a novel nystatin-loaded nanoemulsion for the buccal treatment of candidosis: Ultrastructural effects and release studies. J. Pharm. Sci., 2012, 101(10), 3739-3752.
[27]
Campos, F.; Naveros, B.; Serrano, O.; Merino, C.; Campmany, A. Evaluation of novel nystatin nanoemulsion for skin candidosis infections. Mycoses, 2013, 56(1), 70-81.
[28]
Hussein-Al-Ali, S.; El Zowalaty, M.; Kura, A.; Geilich, M.; Fakurazi, S.; Webster, T.; Hussein, M. Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite. BioMed Res. Int., 2014, 2014, 1-13.
[29]
Reis, C. Luı’s Vasques Roque, L.; Baptista, M.; Rijp, P. Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment. Pharm. Dev. Technol., 2016, 21(3), 282-287.
[30]
Groll, A.; Mickiene, D.; Werner, K.; Petraitiene, R.; Petraitis, V.; Calendario, M.; Field-Ridley, A.; Crisp, J.; Piscitel, S.; Walsh, T. Compartmental pharmacokinetics and tissue distribution of multilamellar liposomal nystatin in rabbits. Antimicrob. Agents Chemother., 2000, 44(4), 950-957.
[31]
Roque, L.; Alopaeus, J.; Reis, C.; Rijo, P.; Molpeceres, J.; Hagesaether, E.; Tho, I.; Reis, C. Mucoadhesive assessment of different antifungal nanoformulations. Bioinspir. Biomim., 2018, 13(5), 1-10.
[32]
Maqsood, I.; Masood, I.; Bashir, S.; Nawaz, H.; Anjum, A.; Shahzadi, I.; Ahmad, A. Preparation and in vitro evaluation of Nystatin micro emulsion based gel. Pak. J. Pharm. Sci., 2015, 28(5), 1587-1593.
[33]
Jadon, P.; Gajbhiye, V.; Jadon, R.; Gajbhiye, K.; Ganesh, A. Enhanced oral bioavailability of griseofulvin via niosomes. AAPS PharmSciTech, 2009, 10(4), 1186-1192.
[34]
Bavarsad, M.; Kouchak, N.; Mohamadipour, P.; Sadeghi-Nejad, B. Preparation and physicochemical characterization of topical chitosan-based film containing griseofulvin-loaded liposomes. J. Adv. Pharm. Technol. Res., 2016, 7(3), 91-98.
[35]
Carmona, E.; Limper, A. Overview of treatment approaches for fungal infections. Clin. Chest Med., 2017, 38(3), 393-402.
[36]
Salem, H.; Ahmed, S.; Omar, M. Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery. Drug Des. Devel. Ther., 2016, 10, 277-295.
[37]
Hashem, F.; Shaker, D.; Ghorab, M.; Nasr, M.; Ismail, A. Formulation, characterization, and clinical evaluation of microemulsion containing clotrimazole for topical delivery. AAPS PharmSciTech, 2011, 12(3), 879-886.
[38]
Borhade, V.; Pathak, S.; Sharma, S.; Patravale, V. Clotrimazole nanoemulsion for malaria chemotherapy. Part II: Stability assessment, in vivo pharmacodynamic evaluations and toxicological studies. Int. J. Pharm., 2012, 431(1-2), 149-160.
[39]
Pankaj, S.; Rini, T.; Dandagi, P. Formulation and evaluation of proniosome based drug delivery system of the antifungal drug clotrimazole. Int. J. Pharma Sci., 2013, 6(1), 1945-1951.
[40]
Firooz, A.; Nafisi, S.; Maibach, H. Novel drug delivery strategies for improving econazole antifungal action. Int. J. Pharm., 2015, 495(1), 599-607.
[41]
Sanna, V.; Gavini, E.; Cossu, M.; Rassu, G.; Giunchedi, P. Solid lipid nanoparticles (SLN) as carriers for the topical delivery of econazole nitrate: In-vitro characterization, ex-vivo and in-vivo studies. J. Pharm. Pharmacol., 2007, 59(8), 1057-1064.
[42]
Passerini, N.; Gavini, E.; Albertini, B.; Rassu, G.; Sabatino, M.; Sanna, V.; Giunchedi, P.; Rodriguez, L. Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate. J. Pharm. Pharmacol., 2009, 61(5), 559-567.
[43]
Gajra, B.; Pandya, S.; Singh, S.; Rabari, H. Mucoadhesive hydrogel films of econazole nitrate: Formulation and optimization using factorial design. J. Drug Deliv., 2014, 2014, 1-14.
[44]
Baloglu, E.; Karavana, S.; Senyigit, Z.; Hilmioglu-Polat, S.; Metin, D.; Zekioglu, O.; Guneri, T.; Jones, D. In-situ gel formulations of econazole nitrate: Preparation and in-vitro and in-vivo evaluation. J. Pharm. Pharmacol., 2011, 63(10), 1274-1282.
[45]
Patel, M.; Patel, R.; Parikh, J.; Solanki, A.; Patel, B. Investigating effect of microemulsion components: In vitro permeation of ketoconazole. Pharm. Dev. Technol., 2011, 16(3), 250-258.
[46]
Ahmed, T.; Aljaeid, B. A potential in situ gel formulation loaded with novel fabricated poly(lactide-co-glycolide) nanoparticles for enhancing and sustaining the ophthalmic delivery of ketoconazole. Int. J. Nanomedicine, 2017, 12, 1863-1875.
[47]
Abdelbary, G.; Amin, M.; Zakaria, M. Ocular ketoconazole-loaded proniosomal gels: Formulation, ex vivo corneal permeation and in vivo studies. Drug Deliv., 2017, 24(1), 309-319.
[48]
Ghorpade, V.; Yadav, A.; Dias, R.; Mali, K.; Pargaonkar, S.; Shinde, P.; Dhane, N. Citric acid crosslinked carboxymethylcellulose-
poly(ethylene glycol) hydrogel films for delivery of poorly
soluble drugs. Int. J. Biol. Macromol, 2018, 118(Pt A), 783-791.
[49]
Kumar, S.; Kaur, P.; Bernela, M.; Rani, R.; Thakur, R. Ketoconazole
encapsulated in chitosan-gellan gum nanocomplexes exhibits
prolonged antifungal activity. Int. J. Biol. Macromol, 2016, 93(PtA), 988-994.
[50]
Rabinow, B.; Kipp, J.; Papadopoulos, P.; Wong, J.; Glosson, J.; Gass, J.; Sun, S.; Wielgos, T.; White, R.; Cook, C.; Barker, K.; Wood, K. Itraconazole IV nanosuspension enhances efficacy through altered pharmacokinetics in the rat. Int. J. Pharm., 2007, 339(1-2), 251-260.
[51]
Mohanty, B.; Majumdar, D.; Mishra, S.; Panda, A.; Patnaik, S. Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery. Pharm. Dev. Technol., 2015, 20(4), 458-464.
[52]
Rundtfelt, C.; Steckel, H.; Scherliess, H.; Wyska, E.; Wlaź, P. Inhalable highly concentrated itraconazole nanosuspension for the treatment of broncho pulmonary aspergillosis. Eur. J. Pharm. Biopharm., 2013, 83(1), 44-53.
[53]
Chudasama, A.; Patel, V.; Nivsarkar, M.; Vasu, K.; Shishoo, C. Investigation of micro emulsion system for transdermal delivery of itraconazole. J. Adv. Pharm. Technol. Res., 2011, 2(1), 30-38.
[54]
Taveira, S.; Gelfuso, G.; Lima, E.; Gratieri, T. Liposomal voriconazole (VOR) formulation for improved ocular delivery. Colloids Surf. B Biointerfaces, 2015, 133, 331-338.
[55]
Kumar, R.; Sinha, V. Solid lipid nanoparticle: An efficient carrier for improved ocular permeation of voriconazole. Drug Dev. Ind. Pharm., 2016, 42(12), 1956-1967.
[56]
Tian, B.; Yan, Q.; Wang, J.; Ding, C.; Sai, S. Enhanced antifungal activity of voriconazole-loaded nanostructured lipid carriers against Candida albicans with a dimorphic switching model. Int. J. Nanomedicine, 2017, 12, 7131-7141.
[57]
Kumar, R.; Sinha, V. Preparation and optimization of voriconazole microemulsion for ocular delivery. Colloids Surf. B Biointerfaces, 2014, 117, 82-88.
[58]
Pawar, P.; Kashyap, H.; Malhotra, S.; Sindhu, R. Hp--CD-Voriconazole In situ gelling system for ocular drug delivery: In vitro, stability, and antifungal activities assessment. BioMed Res. Int., 2013, 2013, 1-9.
[59]
Shukr, M. Novel in situ gelling ocular inserts for voriconazole-loaded niosomes: Design, in vitro characterization and in vivo evaluation of the ocular irritation and drug pharmacokinetics. J. Microencapsul., 2016, 33(1), 71-79.
[60]
Veloso, D.; Benedetti, N.; Ávila, R.; Bastos, T.; Silva, T.; Silva, M.; Batista, A.; Valadares, M.; Lima, E. Intravenous delivery of a liposomal formulation of voriconazole improves drug pharmacokinetics, tissue distribution, and enhances antifungal activity. Drug Deliv., 2018, 25(1), 1585-1594.
[61]
Faisal, W.; Soliman, G.; Hamdan, A. Enhanced skin deposition and delivery of voriconazole using ethosomal preparations. J. Liposome Res., 2016, 28(1), 14-21.
[62]
Arora, S.; Haghi, M.; Young, P.; Kappl, M.; Traini, D.; Jain, S. Highly respirable dry powder inhalable formulation of voriconazole with enhanced pulmonary bioavailability. Expert Opin. Drug Deliv., 2016, 13(2), 183-193.
[63]
Paul, P.; Sengupta, S.; Mukherjee, B.; Shaw, T.; Gaonkar, R.; Debnath, M. Chitosan-coated nanoparticles enhanced lung pharmacokinetic profile of voriconazole upon pulmonary delivery in mice. Nanomedicine , 2018, 13, 501-520.
[64]
Yang, M.; Dong, Z.; Zhang, Y.; Zhang, F.; Wang, Y.; Zhao, Z. Preparation and evaluation of posaconazole-loaded enteric microparticles in rats. Drug Dev. Ind. Pharm., 2017, 43(4), 618-627.
[65]
Fule, R.; Amin, P. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: Investigating drug-polymermiscibility with advanced characterization. BioMed Res. Int., 2014, 2014, 1-16.
[67]
Chen, Y.; Liu, D.; Liu, J.; Chang, T.; Ho, H.; Sheu, M. Development of terbinafine solid lipid nanoparticles as a topical delivery system. Int. J. Nanomedicine, 2012, 7, 4409-4418.
[68]
Vaghasiya, H.; Kumar, A.; Sawant, K. Development of solid lipid nano particles based controlled release system for topical delivery of terbinafine hydrochloride. Eur. J. Pharm. Sci., 2013, 49(2), 311-322.
[69]
Nair, A.; Kim, H.; Chakraborty, B.; Singh, J.; Zaman, M.; Gupta, A.; Friden, P.; Murthy, S. Ungual and trans-ungualion tophoretic delivery of terbinafine for the treatment of onychomycosis. J. Pharm. Sci., 2009, 98(5), 4130-4140.
[70]
Shah, V. Jobanputra1, A. Enhanced ungual permeation of terbinafine HCl delivered through liposome-loaded nail lacquer formulation optimized by qbd approach. AAPS PharmSciTech, 2018, 19(1), 213-224.
Call for Papers in Thematic Issues
10 August, 2024
Nanomaterial Assisted Targeted Therapies for Chronic Disorders- Preclinical to Clinical Outcomes
In recent years, the integration of nanomaterials into therapeutic strategies has emerged as a promising avenue in the pursuit of more effective treatments for chronic disorders. This dynamic field, explored in the context of "Nanomaterial Assisted Targeted Therapies for Chronic Disorders - Preclinical to Clinical Outcomes," seeks to bridge the ...read more
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Current Drug Therapy
Related Books
Drug Addiction Mechanisms in the Brain
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Biotechnology and Drug Development for Targeting Human Diseases
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Enzymatic Targets for Drug Discovery Against Alzheimer's Disease
Medicinal Plants, Phytomedicines and Traditional Herbal Remedies for Drug Discovery and Development against COVID-19
Advanced Pharmacy
Plant-derived Hepatoprotective Drugs
Brain Tumor Targeting Drug Delivery Systems: Advanced Nanoscience for Theranostics Applications
Article Metrics
47
5
1
1