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Table 1.

Size, Zeta potential and loading efficiency of latanoprost loaded DPPC Liposome after extrusion.

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Table 1 Expand

Table 2.

Drug loading values before and after synthesis of liposome vesicles.

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Table 2 Expand

Figure 1.

Malvern Zeta sizer analysis of drug loaded liposome.

The values reported are after 12 weeks of storage at 4°C with drug/lipid mole ratio (size, nm) (a) 0.044 (63±10), (b) 0.11 (90±30), (c) 0.18 (200±80) and (d) 0.37 (1250±200). Size measurement reported here are mean of three batches and the standard deviations (±) are expressed inside bracket.

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Table 3.

Size measurement of liposome formulation (varying d/l mole ratio) during storage at 4°C and after in vitro drug release in PBS buffer (pH 7.4) at 37°C.

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Table 3 Expand

Figure 2.

In vitro dialysis study of latanoprost from drug loaded DPPC LUVs after extrusion.

Cumulative latanoprost release (%) from DPPC LUVs loaded with varying amount of drug/lipid mole ratios: (a) 0.044, (b) 0.11, (c) 0.14, (d) 0.18 and (e) 0.37. Each value is the mean (standard deviations is plotted as error bars, which are always less than 3% for nearly all batches) of the results obtained from at least three independent experiments.

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Figure 3.

DSC analysis of pure and latanoprost loaded DPPC MLVs.

The liposome was made by PBS buffer hydration of anhydrous drug-lipid layer. 10 µl of the liposomal formulation (100 mg/ml) was heated at 1°C/min between −20°C to 65°C. Three heating and two cooling cycles were carried out with each sample and the last reproducible heating cycle was considered for analysis. The drug/lipid mole ratios and their corresponding enthalpy change during transition are reported within parentheses (a) 0.0 (18.9 J/g), (b) 0.03 (8.7 J/g), (c) 0.086 (8.1 J/g), (d) 0.114 (5.2 J/g) and (e) 0.14 (1.6 J/g).

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Figure 4.

Partition coefficient of latanoprost.

Partition coefficient of latanoprost was calculated by taking the ratio of drug concentrations in lipid bilayer and the aqueous buffer. The drugs to lipid loading concentrations (mole ratios) are 0.04, 0.104, 0.14, 0.18, and 0.32 in DPPC. Each partition coefficient value was obtained from the mean of three MLV formulations made and the standard deviations are reported in error bars.

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Figure 5.

Latanoprost release rate from 100 µl of DPPC LUVs with two different drug/lipid mole ratios compared with 1 drop of commercial Xalatan® solution (1.5 µg/drop).

In vitro drug release rate (µg/day) measured from (a) drug/lipid, 0.04 and (b) drug/lipid, 0.11, (c) commercial eye drop (Xalatan®, 1.5 µg/drop). The release rates are reported based on mean values of at least two batches and standard deviations are reported in error bars.

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Figure 6.

Comparison of intraocular pressure (IOP) between topical latanoprost eyedrop, subconjunctival latanoprost liposome and latanoprost-free blank liposomes.

Group A: topical latanoprost eye drop. Group B: subconjunctival latanoprost liposome. Group C: latanoprost-free blank liposomes.

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Figure 7.

Rabbit eyes condition after subconjunctival injection.

Serial slit-lamp microscopy (group A) revealed no significant increase in vascularity and inflammation of all rabbit eyes (I and II: Day 0 after subconjunctival injection; III and IV: Day 30 after subconjunctival injection). AS-OCT scans (group B) revealed no abnormal scarring, scleral or conjunctival thinning in all rabbit eyes (Photos I and II). *SC = Liposome injection site; C = Cornea.

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Figure 8.

Histology of rabbit eyes.

Group A: topical latanoprost eyedrops. Group B: subconjunctival latanoprost liposomes. Group C: subconjunctival latanoprost-free liposomes. Histology revealed no abnormal scarring or damage to the collagen layers in both H&E stain (Photos I and II) and Picrosirius red stain (Photos III and IV; Grade 1 for all eyes). S = Sclera; C = Conjunctiva.

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