• REHAB ABDELMONEM Department of Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt
  • MOHAMED A. EL-NABARAWI Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt
  • ALSHIMAA M. ATTIA Department of Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, 6th October City, Egypt
  • MAHMOUD TEAIMAA Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt


Objective: This study aimed to develop a novel topical ocular system of natamycin (NAT) by formulating and evaluating of NAT-solid lipid nanoparticle (SLN) loaded on mucoadhesive gels to improve its therapeutic activity and reduce the frequency of dosage to assist patient compliance.

Methods: SLNs were prepared using lipids and Tween 80 or Pluronic F127 as stabilizers via modified high shear homogenization and ultrasound techniques. The prepared SLNs were characterized for particle size (PS), zeta potential (ZP), polydispersity index (PI), and entrapment efficiency percentage (EE %). The morphological examination for chosen SLNs was done using a transmission electron microscope (TEM). Carbapol 940 and Hydroxypropyl methylcellulose (HPMC) was incorporated with selected NAT-SLNs to form mucoadhesive gels. The prepared NAT-SLN gels were evaluated for drug content, mucoadhesion force, release study, and in vitro microbiological activity. In vivo study for the chosen formulae was done to evaluate its efficacy against keratitis in rabbits.

Results: NAT-SLNs exhibited high EE % up to 99.167% and PS ranging from 128.35 to 1719.5 nm, with negatively charged ZP that confirmed the stability of SLNs. The NAT-SLN gels provided the high mucoadhesive force with a controlled release manner compared with the marketed-product MP. The in vivo experimental studies and histopathological examination showed the superiority of G2 (NAT-SLN (5% Pluronic F127 and 1:1 mixed lipid) 4% HPMC) over MP against Candida keratitis.

Conclusion: According to the obtained results, G2 provided an effective pharmaceutical system against fungal keratitis in a controlled release manner compared with MP for reducing dosage frequency.

Keywords: Natamycin, Solid lipid nanoparticle, Mucoadhesive gel, In vivo study


1. Khorgade RR, Gaikwad AA, Nilekar SL, Kulkarni DM. Mycotic keratitis in patients attending a tertiary care hospital. Int J Curr Microbiol Appl Sci 2015;4:428-37.
2. Thomas J. Fungizone (amphotericin) product information. Australin prescription products guide. 36th ed. Hawthorn: Victoria Australian Pharmaceutical Publishing; 2007. p. 1392-4.
3. Müller GG, Kara Jose N, Castro RS. Antifungals in eye infections: drugs and routes of administration. Rev Bras Oftalmol 2013;72:41-132.
4. Patil A, Majumdar S. Echinocandins in ocular therapeutics. J Ocul Pharmacol Ther 2017;33:340-52.
5. Oz Y, Ozdemir HG, Gokbolat E, Kiraz N, Ilkit M, Seyedmousavi S. Time-kill kinetics and in vitro antifungal susceptibility of non-fumigatus Aspergillus species isolated from patients with ocular mycoses. Mycopathologia 2016;181:225-33.
6. Qiu S, Zhao GQ, Lin J, Wang X, Hu LT, Du ZD, et al. Natamycin in the treatment of fungal keratitis: a systematic review and meta-analysis. Int J Ophthalmol 2015;8:597-602.
7. Chandasana H, Prasad YD, Chhonker YS, Chaitanya TK, Mishra NN, Mitra K, et al. Corneal targeted nanoparticles for sustained natamycin delivery and their PK/PD indices: an approach to reduce dose and dosing frequency. Int J Pharm 2014;477:317-25.
8. Patil A, Lakhani P, Majumdar S. Current perspectives on natamycin in ocular fungal infections. J Drug Delivery Sci Technol 2017;41:206-12.
9. Jenning V, Gysler A, Schafer Korting M, Gohla S. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm 2000;49:8-211.
10. Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci 2009;71:349-58.
11. Kumar R, Sinha VR. Solid lipid nanoparticle: an efficient carrier for improved ocular permeation of voriconazole. Drug Dev Ind Pharm 2016;2:1-37•
12. Singh M, Guzman Aranguez A, Hussain A, Srinivas C, Kaur IP. Solid lipid nanoparticles for ocular delivery of isoniazid: evaluation, proof of concept, and in vivo safety and kinetics. Nanomedicine (Lond) 2019;14:465-91.
13. Wu Y, Liu Y, Li X, Kebebe D, Bing Z, Ren J, et al. Research progress of in-situ gelling ophthalmic drug delivery system. Asian J Pharm Sci 2019;14:1-15.
14. Preethi GB, Narendra E. Formulation and evaluation of in situ mucoadhesive ophthalmic hydrogel for sustained delivery of pefloxacin mesylate. Int J Pharm Pharm Sci 2015;8:345-50.
15. Hu Y, Tyagi P, Kadam RS, Christopher A. Holden. Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and anti-glaucoma effects for four days following one-time topical administration. ACS Nano 2012;6:595-606.
16. Abdelbary G, Fahmy RH. Diazepam-loaded solid lipid nanoparticles: design and characterization. AAPS PharmSciTech 2009;10:211-9.
17. Chaiyasan W, Srinivas SP, Tiyaboonchai W. Development and characterization of topical ophthalmic formulations containing lutein-loaded mucoadhesive nanoparticles. Int J Pharm Pharm Sci 2016;8:261-6.
18. Shena LN, Zhanga YT, Wang Q, Xub L, Fenga NP. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes. Inter J Pharm 2014;460:280-8.
19. Morsi N, Ghorab D, Refai H, Teba H. Preparation and evaluation of alginate/chitosan nanodispersions for ocular delivery. Int J Pharm Pharm Sci 2015;7:234-40.
20. Abdelmonem R, El Nabarawi M, Attia A. Development of novel bioadhesive granisetron hydrochloride spanlastic gel and insert for brain targeting and study their effects on rats. Drug Delivery 2016;25:70-7.
21. El-Hadidy GN. A pharmaceutical study on topical antifungal drug. M. Sc. Thesis, Fac. Pharm, Cairo Univ; 2010.
22. Ahmed VA, Goli D. Development and characterization of in situ gel of xanthan gum for ophthalmic formulation containing brimonidine tartrate. Asian J Pharm Clin Res 2018;11:277-84.
23. Dragicevic Curic N, Scheglmann D, Albrecht V, Fahr A. Development of different temoporfin-loaded invasomes novel nanocarriers of temoporfin: characterization, stability and in vitro skin penetration studies. Colloids Surf B 2009;70:198-206.
24. Habib FS, Fouad EA, Abdel Rhaman MS, Fathalla D. Liposomes as an ocular delivery system of fluconazole: in vitro studies. Acta Ophthalmol 2010;88:901-4.
25. Zhuanga CY, Lia N, Wanga M, Zhangb XN, Pana WS, Penga JJ, et al. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 2010;394:179-85.
26. Radomska Soukharev A. Stability of lipid excipients in solid lipid nanoparticles. Adv Drug Delivery Rev 2007;59:411-8.
27. Katas H, Cevher E, Alpar HO. Preparation of polyethyleneimine incorporated poly (d,l-lactide-co-glycolide) nanoparticles by spontaneous emulsion diffusion method for small interfering RNA delivery. Int J Pharm 2009;369:144-54.
28. Schafer Korting M, Mehnert W, Korting HC. Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Delivery Rev 2007;59:427-43.
29. Kumar VV, Chandrasekar D, Ramakrishna S, Kishan V, Rao YM, Diwan PV. Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics. Int J Pharm 2007;335:167-75.
30. Silverman RB. The organic chemistry of drug design and drug action. 2nd ed. London: Elsevier Academic Press; 2004. p. 55-61.
31. Ruktanonchai U, Sakulkhu U, Bejrapha P, Opanasopit P, Bunyapraphatsara N, Junyaprasert V, et al. Effect of lipid types on physicochemical characteristics, stability and antioxidant activity of gamma-oryzanol-loaded lipid nanoparticles. J Microencapsulation 2009;26:614-26.
32. Ammar HO, Ghorab M, El-Nahha SA, Higazy IM. Proniosomes as a carrier system for transdermal delivery of tenoxicam. Int J Pharm 2011;405:142-52.
33. Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm 2005;306:71-82.
34. Pharmacopeia US. The National Formulary. Usp30-NF25, Monograph of Natamycin; 2007. p. 2716.
35. Lee JW, Park JH, Robinson JR. Bioadhesive dosage form: the next generation. J Pharm Sci 2000;89:850-66.
36. Mansuri S, Kesharwani P, Jain K, Tkade RK, Jain N. Mucoadhesion; a promising approach in drug delivery and functional polymers. Elsevier Sci 2016;100:172-51.
37. Wang YY, Hong CT, Chiu WT, Fang JY. In vitro and in vivo evaluations of topically applied capsaicin and nonivamide from hydrogels. Int J Pharm 2001;224:89-104.
36 Views | 22 Downloads
How to Cite
ABDELMONEM, R., EL-NABARAWI, M. A., ATTIA, A. M., & TEAIMAA, M. (2020). OCULAR DELIVERY OF NATAMYCIN SOLID LIPID NANOPARTICLE LOADED MUCOADHESIVE GEL: FORMULATION, CHARACTERIZATION AND IN VIVO STUDY. International Journal of Applied Pharmaceutics, 12(5), 173-180. https://doi.org/10.22159/ijap.2020v12i5.38824
Original Article(s)