Search

To overcome problems associated with topical delivery of tacrolimus (TCS), a thermoresponsive in situ gel system containing pluronic F127 (PL), and chitosan (CS) was developed, to enhance the preco...

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.

Tacrolimus is an emerging candidate for the treatment of immune-mediated inflammatory ocular disorders (IIODs) however its ocular delivery remained a challenge due to its hydrophobic nature, high molecular weight and physiological and anatomical constraints of the eye. The present work describes vesicles composed of propylene glycol, phospholipid and water, proglycosomes (PNVs), as novel carriers for ocular delivery of tacrolimus. Addition of propylene glycol decreases vesicle aggregation, increases encapsulation of tacrolimus and prevented drug leakage. Developed PNVs were of nanosize (111.5±3.2nm) and 5-fold more elastic than conventional liposomes. PNVs showed prolonged drug release over period of 12h and higher corneal permeation, 5-fold and 13-fold, compared to conventional liposomes and tacrolimus solution, respectively. Studies in rabbits demonstrated prolonged precorneal retention (upto 8h) and manifestly improved intraocular drug levels, well above therapeutic levels, at all tested time-points following topical application of PNV formulation compared to drug solution. Further, PNVs were found to be safe for ocular use. In conclusion, the developed PNVs are prospective carriers for enhanced ocular delivery of tacrolimus.

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.