<p>Natamycin solid lipid nanoparticles &ndash; sustained ocular delivery system of higher corneal penetration against deep fungal keratitis: preparation and optimization</p>

Abstract

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 [X 1 ], surfactant concentration [X 2 ], and sonication frequency [X 3 ]) on particle size (R 1), zeta potential (ZP; R 2), and drug entrapment efficiency (EE%) (R 3) 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 (P app) and steady-state flux (J ss) 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.

Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis

“…Effect of lipids to surfactant ratio on particle size, polydispersity index and zeta potential of NLC placebos (mean ± SD, n = 3). Thus, increasing surfactant concentrations had a significant effect on PS which could be attributed to a substantial reduction in surface tension and surface-free energy during homogenization due to high shear conditions [45]. The increase in homogenization speed from 14,000 to 15,000 rpm resulted in a simultaneous increase in breaking energy, resulting in NLC formulation with smaller PS and thus, a narrow PDI [46].…”

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

“…The corneal permeation efficacy of the optimized natamycin cubosomes was performed on freshly excised goat corneas obtained from local slaughter house [26]. Whole goat eyeballs were placed in cold artificial tear saline (4°C).…”

Screening Study for Formulation Variables in Preparation and Characterization of Candesartan Cilexetil Loaded Nanostructured Lipid Carriers

“…Stearic acid, Labrafil ® M 2130 CS, Gelucire ® 39/01, Gelucire ® 43/01 proved to be lower CC solubilizing ability, with solid lipid values per 100 mg of CC (w/w) of (2000±3.14 mg, 2000±5.12 mg, 2500±3.15 mg and 2750±4.13 mg), respectively, than the above mentioned ones. So, the following three solid lipids, Precirol ® ATO 5, Compritol ® 888 ATO and GMS selected to be used as lipid core for the preparations of CC-NLCs in this study after discarding of Gelucire ® 44/14 because the addition of Gelucire ® 44/14 to liquid lipid reduces the melting point of NLCs formulations which was not appropriate to be administered orally 23,26 .…”

“…Where, the imperfect and less ordered matrix structure of Precirol® ATO 5 and Compritol® 888 ATO molecules, which are formed from a combination of mono-, di-and triglyceride that expected to exhibit lower crystallinity and more structure porosity which allows higher solubility and easier accommodation of more drug molecules 17,26 . Also, Precirol® ATO 5 is a di-glyceride with two different chain length fatty acids palmitic and stearic acid (C16 and C18); therefore, it is expected to have less ordered lipid network compared to GMS, and thus lead to the more drug molecules could be entrapped 18,26 . Further, subsequent to cooling, Precirol®ATO 5 and Compritol®888 ATO recrystallize in a progression of polymorphs.…”