Liposomes containing bile salts as novel ocular delivery systems for tacrolimus (FK506): in vitro characterization and improved corneal permeation

Abstract

Abstract:The objective of this study was to investigate the potential of liposomes containing bile salts as an ophthalmic delivery system for tacrolimus to improve corneal permeability. Liposomes containing bile salts, including sodium taurocholate, sodium deoxycholate, and sodium glycocholate, were produced by the thin-film dispersion method with a particle size of approximately 100 nm and an entrapment efficiency of more than 90%. Less than 5% tacrolimus was released from conventional liposomes and from liposomes containing sodium taurocholate, sodium deoxycholate, or sodium glycocholate over 12 hours. The cellular uptake of conventional liposomes was significantly higher than that of liposomes containing bile salts. However, liposomes containing bile salts exerted a 3-4-fold increase of tacrolimus in ex vivo corneal transport of tacrolimus compared with conventional liposomes. When rabbit eyes were treated with a DiI perchlorate-loaded liposome suspension, liposomes containing bile salts showed fast and sustained penetration across the cornea. Unfortunately, liposomes containing sodium deoxycholate caused toxicity or irritation to both spontaneously derived human corneal epithelial cells and the rabbit cornea. Therefore, liposomes containing sodium taurocholate and sodium glycocholate are potential carriers in ocular drug delivery systems, given their low toxicity and vastly improved permeability.

Fabrication of novel elastosomes for boosting the transdermal delivery of diacerein: statistical optimization, ex-vivo permeation, in-vivo skin deposition and pharmacokinetic assessment compared to oral formulation

“…DCN elastosomes were prepared using film hydration technique (Dai et al., 2013 ). Briefly, DCN (25 mg), 150 mg of vesicles forming materials (Span 60 and CH) in ratio 5:1 and 15 mg of STC together with different amounts of the used EA (Brij S2 or Brij C10 or Cremophor EL or Cremophor RH 40) were accurately weighted into 250 mL long-necked round-bottom flask and dissolved in 10 mL of chloroform–methanol mixture (7:3).…”

Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition

“…DCN-loaded niosomes were prepared using film hydration technique [25] by varying the used hydration medium, amount of lipid used for bilayer formation (surfactant and CH) and number of surfactant parts (surfactant to CH ratio). In a 250 mL long-necked quick fit round-bottom flask, DCN (25 mg) and accurately weighted quantities of the surfactant (Span 40 or Span 60 or Span 80 or Tween 20 or Tween 80 or Brij 58 or Brij 72) and CH (150 or 200 or 250 mg) in varying ratios (2:1 or 4:1 or 6:1) were dissolved in 10 mL of chloroform-methanol mixture (7:3).…”

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

“…The ex vivo corneal transport experiments indicated that bilosomes enhance the permeation of tacrolimus across the cornea up to fourfold in comparison to conventional liposomes. Bilosomes composed of sodium-TCA and sodium-GCA were well tolerated, whereas those containing sodium-DCA were toxic to human corneal epithelial cells and rabbit cornea ( Dai et al, 2013 ). Bilosomes loaded with the antifungal drug terconazole were prepared using sorbitan esters, cholesterol, and sodium-TCA, and the edge activators (macrogolglycerol ricinoleate and macrogolglycerol hydroxystearate) that impart extra elasticity to the vesicles were added in order to obtain ultradeformable bilosomes.…”