In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants

Abstract

Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.

Gold nano‐decorated aligned polyurethane nanofibers for enhancement of neurite outgrowth and elongation

“…Parallel copper electrodes in 1.8 cm distance from each other were used as a collector. In order to obtain PU nanofibers with aligned and smooth morphology, we optimized the electrospinning parameters such as polymer concentration, the distance between needle and collector, applied voltage and flow rate . Electrospinning solution was prepared by dissolving PU in tetrahidrofurano/dimethylformamide (60:40 [v/v]) solvent mixture and making 8% (w/v) concentration of PU.…”

“…In order to obtain PU nanofibers with aligned and smooth morphology, we optimized the electrospinning parameters such as polymer concentration, the distance between needle and collector, applied voltage and flow rate. [22][23][24][25][26][27] Electrospinning solution was prepared by dissolving PU in tetrahidrofurano/dimethylformamide (60:40 [v/v]) solvent mixture and making 8% (w/v) concentration of PU. Polymer solutions were placed in a glass syringe (5 mL) bearing metallic capillary (0.41 mm i.d.)…”

Nanoparticles for drug delivery to the anterior segment of the eye

“…In vivo ocular irritation studies using the Draize test on New Zealand white albino rabbits demonstrated that the meloxicam nanocrystals-laden contact lenses were significantly less irritating to the ocular tissues when compared with the marketed drug solution alone [225]. Yavuz et al prepared CsA-loaded PLGA 85:15 or PCL (MW 30,000–70,000 Da) nanoparticles by o/w emulsification solvent evaporation technique and then incorporated the nanoparticles into PCL implant/fiber composite system by electrospinning/implant molding method [232]. They found that CsA was present in cornea, sclera and lens even 90 days after subconjunctival implantation of the composite systems in dry-eye induced mice.…”

“…They found that CsA was present in cornea, sclera and lens even 90 days after subconjunctival implantation of the composite systems in dry-eye induced mice. The fiber composite system had better CsA tissue concentration and healing process than the implant composite system [232]. Yang et.…”

Increasing Distribution of Drugs Released from In Situ Forming PLGA Implants Using Therapeutic Ultrasound

“…They are particularly important in cancer therapy where the therapeutic index of the drug is often quite small and the stability of biologic agents is limited. 24, 40 In situ forming implants (ISFI) used for local drug delivery directly into the tissue of interest (e.g. a tumor) are an attractive alternative route to oral and intravenous administration.…”