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Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide.

Youshia J, Kamel AO, El Shamy A, Mansour S - Int J Nanomedicine (2012)

Bottom Line: Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release.The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%.The ZP values of all formulae were positive, and greater than 30 mV.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

ABSTRACT
Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol (®) and cetostearyl alcohol (CSA), and stabilized by Tween 80(®). The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 3(2) full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours.

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Related in: MedlinePlus

Reduction in IOP after administration of topical MZA-loaded NLM-6 and NLM-9 compared to MZA solution.Abbreviations: IOP, intraocular pressure; MZA, methazolamide; NLM, nanostructured lipid matrix.
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f10-ijn-7-2483: Reduction in IOP after administration of topical MZA-loaded NLM-6 and NLM-9 compared to MZA solution.Abbreviations: IOP, intraocular pressure; MZA, methazolamide; NLM, nanostructured lipid matrix.

Mentions: MZA-loaded NLM formulae NLM-6 and NLM-9 were selected for the in vivo studies as they showed higher EE% and prolonged drug release patterns. Figure 10 shows the reduction in the IOP of selected NLM formulations compared to that of MZA solution. It can been seen that the MZA solution caused the greatest reduction in the IOP effect after 3 hours, when a value of −4.85 mmHg was recorded, and the reduction lasted for a total of 5 hours. On the other hand, the IOP-lowering effect of MZA-loaded NLMs reached its peak after 3 hours, when values of −6.4 (NLM-6) and −8.3 mmHg (NLM-9) were recorded; reductions lasted for 10 hours and about 12 hours, respectively, as shown in Table 5. Entrapping MZA in NLMs significantly enhanced its IOP-lowering activity and increased its duration of action compared to the MZA solution (P < 0.05). It is likely that the increase in IOP-lowering activity is due to improved ocular penetration of MZA entrapped in NLMs. This may be attributed to their lipophilic nature facilitating the penetration of the highly hydrophobic epidermis of the cornea.6 Furthermore, the increased duration of action might be due to adherence of NLMs to ocular membranes, preventing tear wash out owing to their small size, cationic charge, and particulate nature.7


Design of cationic nanostructured heterolipid matrices for ocular delivery of methazolamide.

Youshia J, Kamel AO, El Shamy A, Mansour S - Int J Nanomedicine (2012)

Reduction in IOP after administration of topical MZA-loaded NLM-6 and NLM-9 compared to MZA solution.Abbreviations: IOP, intraocular pressure; MZA, methazolamide; NLM, nanostructured lipid matrix.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367493&req=5

f10-ijn-7-2483: Reduction in IOP after administration of topical MZA-loaded NLM-6 and NLM-9 compared to MZA solution.Abbreviations: IOP, intraocular pressure; MZA, methazolamide; NLM, nanostructured lipid matrix.
Mentions: MZA-loaded NLM formulae NLM-6 and NLM-9 were selected for the in vivo studies as they showed higher EE% and prolonged drug release patterns. Figure 10 shows the reduction in the IOP of selected NLM formulations compared to that of MZA solution. It can been seen that the MZA solution caused the greatest reduction in the IOP effect after 3 hours, when a value of −4.85 mmHg was recorded, and the reduction lasted for a total of 5 hours. On the other hand, the IOP-lowering effect of MZA-loaded NLMs reached its peak after 3 hours, when values of −6.4 (NLM-6) and −8.3 mmHg (NLM-9) were recorded; reductions lasted for 10 hours and about 12 hours, respectively, as shown in Table 5. Entrapping MZA in NLMs significantly enhanced its IOP-lowering activity and increased its duration of action compared to the MZA solution (P < 0.05). It is likely that the increase in IOP-lowering activity is due to improved ocular penetration of MZA entrapped in NLMs. This may be attributed to their lipophilic nature facilitating the penetration of the highly hydrophobic epidermis of the cornea.6 Furthermore, the increased duration of action might be due to adherence of NLMs to ocular membranes, preventing tear wash out owing to their small size, cationic charge, and particulate nature.7

Bottom Line: Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release.The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%.The ZP values of all formulae were positive, and greater than 30 mV.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.

ABSTRACT
Solid lipid nanoparticles (SLNs) formulated from one type of lipid (homolipid) suffer from low drug encapsulation and drug bursting due to crystallization of the lipid into the more ordered β modification, which leads to decreased drug entrapment and faster drug release. This study assessed the feasibility of using nanostructured lipid matrices (NLMs) for ocular delivery of methazolamide-(MZA) adopting heterolipids composed of novel mixtures of Compritol (®) and cetostearyl alcohol (CSA), and stabilized by Tween 80(®). The systems were prepared using the modified high shear homogenization followed by ultrasonication method, which avoids the use of organic solvents. A 3(2) full factorial design was constructed to study the influence of two independent variables, namely the ratio of CSA:Compritol and the concentration of Tween 80, each in three levels. The dependent variables were the entrapment efficiency percentages (EE%), mean particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In vivo intraocular pressure (IOP) lowering activity for the selected formulae was compared to that of MZA solution. The results showed that increasing the ratio of CSA to Compritol increased the EE% and PS, while increasing the concentration of Tween 80, decreased PS with no significant effect on EE%. The ZP values of all formulae were positive, and greater than 30 mV. The best formula, composed of 4% CSA, 2% Compritol, 0.15% stearylamine, and 2% Tween 80, with EE% of 25.62%, PS of 207.1 nm, PDI of 0.243, and ZP of 41.50 mV, showed in vitro sustained release properties for 8 hours and lowered the intraocular pressure by 8.3 mmHg within 3 hours, with this drop in pressure lasting for 12 hours.

Show MeSH
Related in: MedlinePlus