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Updated: Jan 25, 2026
Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
Natamycin solid lipid nanoparticles - sustained ocular delivery system of higher corneal penetration against deep
Ahmed Khames1,2, Mohammad A Khaleel3, Mohamed F El-Badawy4,5
1Department of Pharmaceutics and Industrial pharmacy, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia, dr_akhames@yahoo.com.
Background:
Fungal keratitis (FK) is a serious pathogenic condition usually associated with significant ocular morbidity. Natamycin (NAT) is the first-line and only medication approved by the Food and Drug Administration for the treatment of FK. However, NAT suffers from poor corneal penetration, which limits its efficacy for treating deep keratitis.
Purpose:
The objective of this work was to prepare NAT solid lipid nanoparticles (NAT-SLNs) to achieve sustained drug release and increased corneal penetration.
Methods:
NAT-SLNs were prepared using the emulsification-ultrasonication technique. Box- Behnken experimental design was applied to optimize the effects of independent processing variables (lipid concentration [X1], surfactant concentration [X2], and sonication frequency [X3]) on particle size (R1), zeta potential (ZP; R2), and drug entrapment efficiency (EE%) (R3) as responses. Drug release profile, ex vivo corneal permeation, antifungal susceptibility, and cytotoxicity of the optimized formula were evaluated.
Results:
The optimized formula had a mean particle size of 42 r.nm (radius in nanometers), ZP of 26 mV, and EE% reached ~85%. NAT-SLNs showed an extended drug release profile of 10 hours, with enhanced corneal permeation in which the apparent permeability coefficient (Papp) and steady-state flux (Jss) reached 11.59×10-2 cm h-1 and 3.94 mol h-1, respectively, in comparison with 7.28×10-2 cm h-1 and 2.48 mol h-1 for the unformulated drug, respectively. Antifungal activity was significantly improved, as indicated by increases in the inhibition zone of 8 and 6 mm against Aspergillus fumigatus ATCC 1022 and a Candida albicans clinical isolate, respectively, and minimum inhibitory concentration values that were decreased 2.5-times against both of these pathogenic strains. NAT-SLNs were found to be non-irritating to corneal tissue. NAT-SLNs had a prolonged drug release rate, that improved corneal penetration, and increased antifungal activity without cytotoxic effects on corneal tissues.
Conclusion:
Thus, NAT-SLNs represent a promising ocular delivery system for treatment of deep corneal keratitis.
Insights
Natamycin solid lipid nanoparticles (NAT-SLNs) enhance corneal penetration and antifungal activity for fungal keratitis treatment. This novel delivery system offers improved efficacy for deep keratitis without ocular toxicity.
Area of Science:
- Ophthalmology
- Nanotechnology
- Pharmaceutics
Background:
- Fungal keratitis (FK) is a severe eye infection causing significant morbidity.
- Natamycin (NAT) is the primary FDA-approved treatment but has poor corneal penetration, limiting its effectiveness for deep infections.
Purpose of the Study:
- To develop NAT solid lipid nanoparticles (NAT-SLNs) for sustained drug release and enhanced corneal penetration.
- To overcome the limitations of conventional NAT formulations in treating deep keratitis.
Main Methods:
- NAT-SLNs were prepared using emulsification-ultrasonication.
- Box-Behnken design optimized lipid concentration, surfactant concentration, and sonication frequency.
- Evaluated particle size, zeta potential, entrapment efficiency, drug release, corneal permeation, antifungal activity, and cytotoxicity.
Main Results:
- Optimized NAT-SLNs exhibited a particle size of 42 nm, zeta potential of 26 mV, and ~85% entrapment efficiency.
- Achieved sustained drug release over 10 hours with significantly enhanced corneal permeation compared to unformulated NAT.
- Demonstrated improved antifungal activity against Aspergillus fumigatus and Candida albicans with no observed corneal cytotoxicity.
Conclusions:
- NAT-SLNs show promise as an effective ocular delivery system for deep fungal keratitis.
- The formulation improves drug release, corneal penetration, and antifungal efficacy.
- This approach offers a safer and more potent treatment option for fungal keratitis.
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