Research Article
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Year 2020, Volume: 24 Issue: 2, 251 - 263, 27.06.2025

Kazi Marzuka , Renuka Dhakne Mohammed Hassan Dehghan

https://doi.org/10.35333/jrp.2020.142
Cited By: 2

Abstract

References

  • [1] Chandasana H, Prasad YD, Chhonker YS, Chaitanya TK, Mishra NN, Mitra K, Shukla PK, Bhatta RS. 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(1–2): 317–325. [CrossRef]
  • [2] Ansari Z, Miller D, Galor A. Current Thoughts in Fungal Keratitis: Diagnosis and Treatment. Curr Fungal Infect Rep. 2013; 7(3): 209–218. [CrossRef]
  • [3] Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002; 28(5): 473–493. [CrossRef]
  • [4] Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997; 38(3): 627–34.
  • [5] Keister JC, Cooper ER, Missel PJ, Lang JC, Hager DF. Limits on optimizing ocular drug delivery. J Pharm Sci. 1991; 80(1): 50–53. [CrossRef]
  • [6] Shen HH, Chan EC, Lee JH, Bee YS, Lin TW, Dusting GJ, et al. Nanocarriers for treatment of ocular neovascularization in the back of the eye: new vehicles for ophthalmic drug delivery. Nanomed. 2015; 10(13): 2093–2107. [CrossRef]
  • [7] Boyd BJ, Dong Y-D, Rades T. Nonlamellar liquid crystalline nanostructured particles: advances in materials and structure determination. J Liposome Res. 2009; 19(1): 12–28. [CrossRef]
  • [8] Chung H, Kim J, Um JY, Kwon IC, Jeong SY. Self-assembled “nanocubicle” as a carrier for peroral insulin delivery. Diabetologia. 2002; 45(3): 448–451.[CrossRef]
  • [9] Lalu L, Tambe V, Pradhan D, Nayak K, Bagchi S, Maheshwari R, Kalia K,Tekade RK. Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions. J Control Release Off J Control Release Soc. 2017; 268: 19–39. [CrossRef]
  • [10] Almeida H, Amaral MH, Lobao P, Frigerio C, Sousa Lobo JM. Nanoparticles in Ocular Drug Delivery Systems for Topical Administration: Promises and Challenges. Curr Pharm Des. 2015; 21(36): 5212–5224. [CrossRef].
  • [11] Dong Y, Chang Y, Qian W, Tong J, Zhou J. Effects of surfactants on size and structure of amylose nanoparticles prepared by precipitation. Bull Mater Sci. 2016; 39(1): 35-39. [CrossRef]
  • [12] Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B Biointerfaces. 2005; 45(3–4): 167–173. [CrossRef]
  • [13] Zirak M, Pezeshki A. Effect of Surfactant Concentration on the Particle Size, Stability and Potential Zeta of Beta carotene Nano Lipid Carrier. IntJCurrMicrobiolAppSci. 2015; 4: 924–932.
  • [14] McClements DJ. Crystals and crystallization in oil-in-water emulsions: implications for emulsion-based delivery systems. Adv Colloid Interface Sci. 2012; 174: 1–30. [CrossRef]
  • [15] Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, Peng X. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine. 2011; 6: 683–692. [CrossRef]
  • [16] Ali Z, Sharma P, Warsi M. Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery. J Appl Pharm Sci. 2016; 6: 204–208. [CrossRef]
  • [17] Magenheim B, Levy MY, Benita S. A new in vitro technique for the evaluation of drug release profile from colloidal carriers - ultrafiltration technique at low pressure. Int J Pharm. 1993; 94(1): 115–123. [CrossRef]
  • [18] Han S, Shen J, Gan Y, Geng H, Zhang X, Zhu C, et al. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability. Acta Pharmacol Sin. 2010; 31(8): 990–998. [CrossRef]
  • [19] Cevher E, Sensoy D, Zloh M, Mulazimoglu L. Preparation and characterisation of natamycin: gamma-cyclodextrin inclusion complex and its evaluation in vaginal mucoadhesive formulations. J Pharm Sci. 2008; 97(10): 4319–4335. [CrossRef]
  • [20] Liu Q, Wu X, Qian F, Zhang T, Mu G. Influence of natamycin loading on the performance of transglutaminase‐induced crosslinked gelatin composite films. Int J Food Sci Technol.2019; 54(7): 2425-2436. [CrossRef]
  • [21] Bei D, Marszalek J, Youan B BC. Formulation of dacarbazine-loaded cubosomes-part I: influence of formulation variables. AAPS PharmSciTech. 2009; 10(3): 1032–1039. [CrossRef]
  • [22] Ali MA, Noguchi S, Iwao Y, Oka T, Itai S. Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing alpha-Monoglyceride Additives. Chem Pharm Bull (Tokyo). 2016; 64(6): 577–584. [CrossRef]
  • [23] El Nabarawi MA, Abd El Rehem RT, Teaima M, Abary M, El-Mofty HM, Khafagy MM, Lofty NM,Salah M. Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies. Drug Dev Ind Pharm. 2019; 45(6): 922–936. [CrossRef]
  • [24] Abdelbary G, El Gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech. 2008; 9(3): 740–747. [CrossRef]
  • [25] Petrikkou E, Rodriguez T JL, Cuenca EM, Gomez A, Molleja A, Mellado E. Inoculum standardization for antifungal susceptibility testing of filamentous fungi pathogenic for humans. J Clin Microbiol. 2001; 39(4): 1345–1347. [CrossRef]
  • [26] Khames A, Khaleel MA, El-Badawy MF, El-Nezhawy AOH. Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization. Int J Nanomedicine. 2019; 14: 2515–2531. [CrossRef]

Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis

Year 2020, Volume: 24 Issue: 2, 251 - 263, 27.06.2025

Kazi Marzuka , Renuka Dhakne Mohammed Hassan Dehghan

https://doi.org/10.35333/jrp.2020.142
Cited By: 2

Abstract

A 32 factorial design was used to develop Natamycin cubosome nanoparticles with enhanced corneal permeation, so as to effectively treat ocular fungal keratitis. Probe sonication technique was deployed to disperse the dry lipidic film to obtain colloidal dispersion. The colloidal dispersion was characterized for critical quality attributes such as particle size, poly dispersibility index (PDI), zeta potential and entrapment efficiency. The optimized batch exhibited a particle size of 158.2 nm, zeta potential -40 mV, PDI 0.328 in addition, entrapment efficiency of 99.85%. The in vitro drug release of natamycin from optimized cubosome demonstrated a cumulative %drug release of 84.29% at the end of 8 hours. The optimized cubosomal dispersion exhibited enhanced in vitro antifungal activity against Candida albicans and Aspergillus fumigatus as compared to a pure drug suspension. The optimized formulation was further analyzed for polarized light microscopy (PLM), transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS) to state the morphology of formed cubosome nanoparticles and was noted to be Im3m bicontinous cubic mesophasic structure. X-ray diffraction (XRD) studies affirmed the complete encapsulation of natamycin into cubosome vesicles. Ex vivo corneal permeation studies of optimized formulation revealed enhanced corneal permeation in comparison to a pure drug suspension. The ocular irritation studies performed on rabbits indicated the cubosome to be non-irritant. Finally, the developed natamycin cubosome nanoparticles demonstrated sustained drug release and increased corneal penetration. Thus, these cubosome nanocarriers present a propitious delivery system for effective management of ocular fungal keratitis.

Keywords

Natamycin cubosome ocular fungal keratitis nanoparticles factorial design

References

  • [1] Chandasana H, Prasad YD, Chhonker YS, Chaitanya TK, Mishra NN, Mitra K, Shukla PK, Bhatta RS. 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(1–2): 317–325. [CrossRef]
  • [2] Ansari Z, Miller D, Galor A. Current Thoughts in Fungal Keratitis: Diagnosis and Treatment. Curr Fungal Infect Rep. 2013; 7(3): 209–218. [CrossRef]
  • [3] Kaur IP, Kanwar M. Ocular preparations: the formulation approach. Drug Dev Ind Pharm. 2002; 28(5): 473–493. [CrossRef]
  • [4] Hamalainen KM, Kananen K, Auriola S, Kontturi K, Urtti A. Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera. Invest Ophthalmol Vis Sci. 1997; 38(3): 627–34.
  • [5] Keister JC, Cooper ER, Missel PJ, Lang JC, Hager DF. Limits on optimizing ocular drug delivery. J Pharm Sci. 1991; 80(1): 50–53. [CrossRef]
  • [6] Shen HH, Chan EC, Lee JH, Bee YS, Lin TW, Dusting GJ, et al. Nanocarriers for treatment of ocular neovascularization in the back of the eye: new vehicles for ophthalmic drug delivery. Nanomed. 2015; 10(13): 2093–2107. [CrossRef]
  • [7] Boyd BJ, Dong Y-D, Rades T. Nonlamellar liquid crystalline nanostructured particles: advances in materials and structure determination. J Liposome Res. 2009; 19(1): 12–28. [CrossRef]
  • [8] Chung H, Kim J, Um JY, Kwon IC, Jeong SY. Self-assembled “nanocubicle” as a carrier for peroral insulin delivery. Diabetologia. 2002; 45(3): 448–451.[CrossRef]
  • [9] Lalu L, Tambe V, Pradhan D, Nayak K, Bagchi S, Maheshwari R, Kalia K,Tekade RK. Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions. J Control Release Off J Control Release Soc. 2017; 268: 19–39. [CrossRef]
  • [10] Almeida H, Amaral MH, Lobao P, Frigerio C, Sousa Lobo JM. Nanoparticles in Ocular Drug Delivery Systems for Topical Administration: Promises and Challenges. Curr Pharm Des. 2015; 21(36): 5212–5224. [CrossRef].
  • [11] Dong Y, Chang Y, Qian W, Tong J, Zhou J. Effects of surfactants on size and structure of amylose nanoparticles prepared by precipitation. Bull Mater Sci. 2016; 39(1): 35-39. [CrossRef]
  • [12] Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S. Preparation and characterization of stearic acid nanostructured lipid carriers by solvent diffusion method in an aqueous system. Colloids Surf B Biointerfaces. 2005; 45(3–4): 167–173. [CrossRef]
  • [13] Zirak M, Pezeshki A. Effect of Surfactant Concentration on the Particle Size, Stability and Potential Zeta of Beta carotene Nano Lipid Carrier. IntJCurrMicrobiolAppSci. 2015; 4: 924–932.
  • [14] McClements DJ. Crystals and crystallization in oil-in-water emulsions: implications for emulsion-based delivery systems. Adv Colloid Interface Sci. 2012; 174: 1–30. [CrossRef]
  • [15] Hao J, Fang X, Zhou Y, Wang J, Guo F, Li F, Peng X. Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design. Int J Nanomedicine. 2011; 6: 683–692. [CrossRef]
  • [16] Ali Z, Sharma P, Warsi M. Fabrication and Evaluation of Ketorolac Loaded Cubosome for Ocular Drug Delivery. J Appl Pharm Sci. 2016; 6: 204–208. [CrossRef]
  • [17] Magenheim B, Levy MY, Benita S. A new in vitro technique for the evaluation of drug release profile from colloidal carriers - ultrafiltration technique at low pressure. Int J Pharm. 1993; 94(1): 115–123. [CrossRef]
  • [18] Han S, Shen J, Gan Y, Geng H, Zhang X, Zhu C, et al. Novel vehicle based on cubosomes for ophthalmic delivery of flurbiprofen with low irritancy and high bioavailability. Acta Pharmacol Sin. 2010; 31(8): 990–998. [CrossRef]
  • [19] Cevher E, Sensoy D, Zloh M, Mulazimoglu L. Preparation and characterisation of natamycin: gamma-cyclodextrin inclusion complex and its evaluation in vaginal mucoadhesive formulations. J Pharm Sci. 2008; 97(10): 4319–4335. [CrossRef]
  • [20] Liu Q, Wu X, Qian F, Zhang T, Mu G. Influence of natamycin loading on the performance of transglutaminase‐induced crosslinked gelatin composite films. Int J Food Sci Technol.2019; 54(7): 2425-2436. [CrossRef]
  • [21] Bei D, Marszalek J, Youan B BC. Formulation of dacarbazine-loaded cubosomes-part I: influence of formulation variables. AAPS PharmSciTech. 2009; 10(3): 1032–1039. [CrossRef]
  • [22] Ali MA, Noguchi S, Iwao Y, Oka T, Itai S. Preparation and Characterization of SN-38-Encapsulated Phytantriol Cubosomes Containing alpha-Monoglyceride Additives. Chem Pharm Bull (Tokyo). 2016; 64(6): 577–584. [CrossRef]
  • [23] El Nabarawi MA, Abd El Rehem RT, Teaima M, Abary M, El-Mofty HM, Khafagy MM, Lofty NM,Salah M. Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies. Drug Dev Ind Pharm. 2019; 45(6): 922–936. [CrossRef]
  • [24] Abdelbary G, El Gendy N. Niosome-encapsulated gentamicin for ophthalmic controlled delivery. AAPS PharmSciTech. 2008; 9(3): 740–747. [CrossRef]
  • [25] Petrikkou E, Rodriguez T JL, Cuenca EM, Gomez A, Molleja A, Mellado E. Inoculum standardization for antifungal susceptibility testing of filamentous fungi pathogenic for humans. J Clin Microbiol. 2001; 39(4): 1345–1347. [CrossRef]
  • [26] Khames A, Khaleel MA, El-Badawy MF, El-Nezhawy AOH. Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization. Int J Nanomedicine. 2019; 14: 2515–2531. [CrossRef]
There are 26 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Articles
Authors

Kazi Marzuka

Renuka Dhakne

Mohammed Hassan Dehghan

Publication Date June 27, 2025
Published in Issue Year 2020 Volume: 24 Issue: 2

Cite

APA Marzuka, K., Dhakne, R., & Dehghan, M. H. (2025). Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis. Journal of Research in Pharmacy, 24(2), 251-263. https://doi.org/10.35333/jrp.2020.142
AMA Marzuka K, Dhakne R, Dehghan MH. Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis. J. Res. Pharm. June 2025;24(2):251-263. doi:10.35333/jrp.2020.142
Chicago Marzuka, Kazi, Renuka Dhakne, and Mohammed Hassan Dehghan. “Ocular Delivery of Natamycin Based on monoolein/span 80/Poloxamer 407 Nanocarriers for the Effectual Treatment of Fungal Keratitis”. Journal of Research in Pharmacy 24, no. 2 (June 2025): 251-63. https://doi.org/10.35333/jrp.2020.142.
EndNote Marzuka K, Dhakne R, Dehghan MH (June 1, 2025) Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis. Journal of Research in Pharmacy 24 2 251–263.
IEEE K. Marzuka, R. Dhakne, and M. H. Dehghan, “Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis”, J. Res. Pharm., vol. 24, no. 2, pp. 251–263, 2025, doi: 10.35333/jrp.2020.142.
ISNAD Marzuka, Kazi et al. “Ocular Delivery of Natamycin Based on monoolein/span 80/Poloxamer 407 Nanocarriers for the Effectual Treatment of Fungal Keratitis”. Journal of Research in Pharmacy 24/2 (June 2025), 251-263. https://doi.org/10.35333/jrp.2020.142.
JAMA Marzuka K, Dhakne R, Dehghan MH. Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis. J. Res. Pharm. 2025;24:251–263.
MLA Marzuka, Kazi et al. “Ocular Delivery of Natamycin Based on monoolein/span 80/Poloxamer 407 Nanocarriers for the Effectual Treatment of Fungal Keratitis”. Journal of Research in Pharmacy, vol. 24, no. 2, 2025, pp. 251-63, doi:10.35333/jrp.2020.142.
Vancouver Marzuka K, Dhakne R, Dehghan MH. Ocular delivery of natamycin based on monoolein/span 80/poloxamer 407 nanocarriers for the effectual treatment of fungal keratitis. J. Res. Pharm. 2025;24(2):251-63.

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