Author(s): Shereen H. Noshi, Mona Basha, Ghada E. A. Awad, Nihal Mohamed Elmahdy Elsayyad


DOI: 10.52711/0974-360X.2022.00081   

Address: Shereen H. Noshi1, Mona Basha2, Ghada E. A. Awad3, Nihal Mohamed Elmahdy Elsayyad1*
1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt, 12564.
2Pharmaceutical Technology Department, National Research Centre (NRC), El-Tahrir Street, Cairo, Egypt, 12622.
3Chemistry of Natural and Microbial Product Department, National Research Center (NRC), El-Tahrir Street, Cairo, Egypt,12622.
*Corresponding Author

Published In:   Volume - 15,      Issue - 2,     Year - 2022

Miconazole nitrate (MN) is a broad-spectrum antifungal agent which suffers poor solubility and impermeability to the ocular tissue which limits its use in the treatment of ocular infections especially fungal keratitis, which is considered one of the most prevailing ocular infections. The current study aims to utilize polymeric mixed nano-micelles for the ocular delivery of MN using 33 full factorial design by varying the ratios of Pluronic® P123, Pluronic® F127, and Tetronic® T701 while the monitored responses were particle size, cloud point (CP), encapsulation efficiency (%EE) and %released at 6 hours (%Q6) at pH 7.4. The optimized formula was incorporated with Soluplus® (SP) to further enhance the (%EE) and the resultant formula was assessed in vitro as well as in vivo against C. albicans in treatment of induced ocular candidiasis using rabbits as a model animal. Results revealed that the optimized formula which comprised F127 and P123 in a ratio of (2:1) when incorporated with SP (SP-MPM) resulted in an increase in %EE from 35.12±3.18 to 99.19±7.03 with a particle size of 44.39±2.68nm with a sustained release profile and stability for 3 months at 4±2°C. In vivo results demonstrated the enhanced ability of SP-MPM for treatment of ocular candidiasis with enhanced % inhibition and susceptibility to C. albicans compared to 0.2% MN suspension confirmed with histopathological examination of rabbit’s eyes after 7 days of treatment with the absence of any degenerative effect to the ocular tissue. Thus, it can be concluded that SP-pluronic mixed nano-micelles offer a successful and stable ocular delivery platform for antifungal drug MN ensuring both its safety and efficacy.

Cite this article:
Shereen H. Noshi, Mona Basha, Ghada E. A. Awad, Nihal Mohamed Elmahdy Elsayyad. Miconazole Nitrate loaded Soluplus®-Pluronic® nano-micelles as promising Drug Delivery Systems for Ocular Fungal Infections: In vitro and In vivo Considerations. Research Journal of Pharmacy and Technology. 2022; 15(2):501-1. doi: 10.52711/0974-360X.2022.00081

Shereen H. Noshi, Mona Basha, Ghada E. A. Awad, Nihal Mohamed Elmahdy Elsayyad. Miconazole Nitrate loaded Soluplus®-Pluronic® nano-micelles as promising Drug Delivery Systems for Ocular Fungal Infections: In vitro and In vivo Considerations. Research Journal of Pharmacy and Technology. 2022; 15(2):501-1. doi: 10.52711/0974-360X.2022.00081   Available on:

1.    Tuli SS. Fungal keratitis. Clinical Ophthalmology. 2011;5:275-9.
2.    Miyakubo T. Todokoro D.Makimura K.Akiyama H. Fungal keratitis caused by Didymella gardeniae (formerly Phoma gardeniae) successfully treated with topical voriconazole and miconazole. Medical Mycology Case Reports. 2019;24:90-2.
3.    Taha EI. Badran MM. El-Anazi MH.Bayomi MA.El-Bagory IM. Role of Pluronic F127 micelles in enhancing ocular delivery of ciprofloxacin. Journal of Molecular Liquids. 2014;199:251-6.
4.    Nautiyal D.Singh V.Ali S. Formulation and Evaluation of Sustained Release of Ofloxacin Ocular Inserts. Research Journal of Pharmacy and Technology. 2012;5(12):1497-9.
5.    Shinde V.Amsa P.Tamizharasi S.Karthikeyan D.Sivakumar T.Kale A. Formulation and Characterization of Eudragit RS 100 Nanosuspension for Ocular Delivery of Indomethacin. Research Journal of Pharmacy and Technology. 2010;3(3):854-60
6.    Chawla A.Ahuja M. In Vitro and In Vivo Evaluation of the Chitosan Microparticulate Ocular Delivery System of Ketorolac Tromethamine. Research Journal of Pharmacy and Technology. 2009;2(3). /
7.    Pandit J.Garg M.Jain NK. Miconazole nitrate bearing ultraflexible liposomes for the treatment of fungal infection. Journal of Liposome Research. 2014;24(2):163-9.10.
8.    Vandenbosch D.Braeckmans K.Nelis HJ.Coenye T. Fungicidal activity of miconazole against Candida spp. biofilms. The Journal of Antimicrobial Chemotherapy. 2010;65(4):694-700.
9.    Marc OY.Vinci V.Karyn DF. Toxicity of intravitreal miconazole in dmso. Journal of Toxicology: Cutaneous and Ocular Toxicology. 1987;6(1):19-27.
10.    Jafari MR.Danti AG.Ahmed I. Comparison of polyethylene glycol, polyvinylpyrrolidone and urea as excipients for solid dispersion systems of miconazole nitrate. International Journal of Pharmaceutics. 1988;48(1):207-15.
11.    D K.VP P. Preparation and In-Vitro Characterization of Diclofenac Sodium Niosomes for Ocular Use. Research Journal of Pharmacy and Technology. 2009;2(4):710-3
12.    Vasanani MR.Patel N.Patel D.KS R.Jha LL. Mucoadhesive-Nanoparticulate System for Ocular Delivery of Loteprednol Etabonate. Asian Journal of Pharmaceutical Research. 2014;4(2):78-83
13.    Jain SK.Chandra R.Rai AK. Characterization of Ocular Delivery of Reverse Micelles Bearing Insulin. Research Journal of Pharmacy and Technology. 2008;1(4):370-3
14.    Viswanathan S.Kumar NV.Srinivasan P.Prabhu S. Nanoparticle-Mediated Drug Delivery Systems. Research Journal of Engineering and Technology. 2013;4(4):295-9
15.    Dutta S.Kulkarni PK.T S. Dissolution behavior of Olmesartan Medoxomil drug in Polymeric Micelles of Soluplus and Pluronic F127. Research Journal of Pharmacy and Technology. 2021;14(4):2200-4.
16.    Vaishya RD.Khurana V.Patel S.Mitra AK. Controlled ocular drug delivery with nanomicelles. Wiley interdisciplinary reviews Nanomedicine and Nanobiotechnology. 2014;6(5):422-37.
17.    Al Khateb K.Ozhmukhametova EK.Mussin MN.Seilkhanov SK.Rakhypbekov TK.Lau WM, et al. In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery. International Journal of Pharmaceutics. 2016;502(1):70-9.
18.    Narendra Kr Goyal.Sharma N.Bhardwaj V.Sharma PK. Pluronic F127 as Thermoreversible Polymer Gel Forming Agent for Delivery of Drugs. Research Journal of Pharmacy and Technology. 2010;3(3):700-4
19.    Cagel M.Tesan FC.Bernabeu E.Salgueiro MJ.Zubillaga MB.Moretton MA, et al. Polymeric mixed micelles as nanomedicines: Achievements and perspectives. European Journal of Pharmaceutics and Biopharmaceutics. 2017;113:211-28.
20.    Chiappetta DA.Sosnik A. Poly(ethylene oxide)–poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs. European Journal of Pharmaceutics and Biopharmaceutics. 2007;66(3):303-17.
21.    Sahu A.Kasoju N.Goswami P.Bora U. Encapsulation of Curcumin in Pluronic Block Copolymer Micelles for Drug Delivery Applications. Journal of Biomaterials Applications. 2011;25:619-39.
22.    Jin X.Zhou B.Xue L.San W. Soluplus® micelles as a potential drug delivery system for reversal of resistant tumor. Biomedicine & Pharmacotherapy. 2015;69:388-95.
23.    Hughey JR.Keen JM.Miller DA.Kolter K.Langley N.McGinity JW. The use of inorganic salts to improve the dissolution characteristics of tablets containing Soluplus(R)-based solid dispersions. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2013;48(4-5):758-66.
24.    Zhang Z.Cui C.Wei F.Lv H. Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system. Drug Development and Industrial Pharmacy. 2017;43(8):1276-82.
25.    Vaishali A.Manish K.Kamla P. Defining the Properties of pH -sensitive Polymeric Micellar Ocular Delivery System of Miconazole Nitrate for the Management of Fungal Endophthalmitis. Pharmaceutical Nanotechnology. 2014;2(3):157-66
26.    El-Laithy HM.Badawi A.Abdelmalak NS.El-Sayyad N. Cubosomes as Oral Drug Delivery Systems: A Promising Approach for Enhancing the Release of Clopidogrel Bisulphate in the Intestine. Chem Pharm Bull. 2018;66(12):1165-73
27.    Elsayyad NME.Salama A.Noshi SH. Concurrent tissue engineering and infection prophylaxis utilising stable dual action amoxicillin loaded scaffolds. Journal of Drug Delivery Science and Technology. 2020;58:101788.
28.    El-Laithy HM.Badawi A.Abdelmalak NS.Elsayyad NME. Stabilizing excipients for engineered clopidogrel bisulfate procubosome derived in situ cubosomes for enhanced intestinal dissolution: Stability and bioavailability considerations. European Journal of Pharmaceutical Sciences. 2019;136:104954.
29.    Chen F.Rice KC.Liu XM.Reinhardt RA.Bayles KW.Wang D. Triclosan-loaded tooth-binding micelles for prevention and treatment of dental biofilm. Pharmaceutical Research. 2010;27(11):2356-64.
30.    Saudagar RB.Gangurde PA. Formulation, development and evaluation of film-forming gel for prolonged dermal delivery of miconazole nitrate. Research Journal of Topical and Cosmetic Sciences. 2017;8(1):19.
31.    Parmar A.Chavda S.Bahadur P. Pluronic–cationic surfactant mixed micelles: Solubilization and release of the drug hydrochlorothiazide. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2014;441:389-97.
32.    Kumar N.Sharma S. Design, Formulation and Evaluation of Sustained Ophthalmic Delivery of Ciprofloxacin from Ocular Inserts. Research Journal of Pharmacy and Technology. 2013;6(3):285-8
33.    Khalil RM.Abdelbary GA.Basha M.Awad GE.El-Hashemy HA. Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl. Journal of Liposome Research. 2017;27(2):118-29.
34.    Ribeiro A.Figueiras A.Santos D.Veiga F. Preparation and solid-state characterization of inclusion complexes formed between miconazole and methyl-beta-cyclodextrin. AAPS PharmSciTech. 2008;9(4):1102-9.
35.    International Confrence On Harmonization Of Technical Requirements For Registration Of Pharmacueticals For Human Use, ICH Harmonized Triparitate Guideline: Stability Testing Of New Drug Substances And Products Q1a (R2).
36.    Gao Y.Li LB.Zhai G. Preparation and characterization of Pluronic/TPGS mixed micelles for solubilization of camptothecin. Colloids and surfaces B, Biointerfaces. 2008;64(2):194-9.
37.    Alsterholm M.Karami N.Faergemann J. Antimicrobial activity of topical skin pharmaceuticals - an in vitro study. Acta dermato-venereologica. 2010;90(3):239-45.
38.    Liaw J.Chang SF.Hsiao FC. In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles. Gene Therapy. 2001;8(13):999-1004.
39.    Salama AH.Shamma RN. Tri/tetra-block co-polymeric nanocarriers as a potential ocular delivery system of lornoxicam: in-vitro characterization, and in-vivo estimation of corneal permeation. International Journal of Pharmaceutics. 2015;492(1-2):28-39. 2015.07.010.
40.    Dutra LMU.Ribeiro MENP.Cavalcante IM.Brito DHAD.Semião LdM.Silva RFd, et al. Binary mixture micellar systems of F127 and P123 for griseofulvin solubilisation. Polímeros. 2015;25:433-9
41.    Lee ES.Oh YT.Youn YS.Nam M.Park B.Yun J, et al. Binary mixing of micelles using Pluronics for a nano-sized drug delivery system. Colloids and surfaces B, Biointerfaces. 2011;82(1):
42.    Joshi T. Cloud Point Phenomena of Mixed Block Copolymers. Journal of Dispersion Science and Technology. 2015;37:150708213411001.
43.    Almgren M.Brown W.Hvidt S. Self-aggregation and phase behavior of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers in aqueous solution. Colloid and Polymer Science. 1995;273(1):2-15.
44.    Jindal N.Mehta SK. Nevirapine loaded Poloxamer 407/Pluronic P123 mixed micelles: Optimization of formulation and in vitro evaluation. Colloids and surfaces B, Biointerfaces. 2015;129:100-6.
45.    Wei Z.Hao J.Yuan S.Li Y.Juan W.Sha X, et al. Paclitaxel-loaded Pluronic P123/F127 mixed polymeric micelles: formulation, optimization and in vitro characterization. International Journal of Pharmaceutics. 2009;376(1-2):176-85.
46.    Bodratti AM.Alexandridis P. Formulation of Poloxamers for Drug Delivery. Journal of Functional Biomaterials. 2018;9(1).
47.    Alambiaga-Caravaca AM.Calatayud-Pascual MA.Rodilla V.Concheiro A.Lopez-Castellano A.Alvarez-Lorenzo C. Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability. Pharmaceutics. 2020;12(8).
48.    Younes NF.Abdel-Halim SA.Elassasy AI. Solutol HS15 based binary mixed micelles with penetration enhancers for augmented corneal delivery of sertaconazole nitrate: optimization, in vitro, ex vivo and in vivo characterization. Drug Delivery. 2018;25(1):1706-17.
49.    Baino F.Kargozar S. Regulation of the Ocular Cell/Tissue Response by Implantable Biomaterials and Drug Delivery Systems. Bioengineering. 2020;7(3).
50.    Jain P.Jaiswal CP.Mirza MA.Anwer MK.Iqbal Z. Preparation of levofloxacin loaded in situ gel for sustained ocular delivery: in vitro and ex vivo evaluations. Drug Development and Industrial Pharmacy. 2020;46(1):50-6.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available