Linoleic Acid-Based Transferosomes for Topical Ocular Delivery of Cyclosporine A

Abstract

Delivering high-molecular-weight hydrophobic peptides, such as cyclosporine A, across the corneal epithelium remains a challenge that is complicated by other physio-anatomical ocular structures that limit the ocular bioavailability of such peptides. Transferosomes have previously been used to improve transdermal permeability, and have the potential for improving the ocular corneal permeability of applicable drugs. In this study, transferosomes for the potential ocular delivery of cyclosporine A were investigated. Linoleic acid was evaluated for its effect on the stability of the transferosomes and was substituted for a portion of the cholesterol in the vesicles. Additionally, Span® 80 and Tween® 80 were evaluated for their effect on transferosome flexibility and toxicity to ocular cells as edge activators. Attenuated Total Reflectance–Fourier Transform Infrared spectroscopy (ATF-FTIR), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) were used to evaluate the physicochemical parameters of the blank and the cyclosporine A-loaded transferosomes. Cyclosporine A release and corneal permeability were studied in vitro and in a New Zealand albino rabbit corneal model, respectively. The linoleic acid contributed to improved stability and the nano-size of the transferosomes. The Tween®-based formulation was preferred on the basis of a more favorable toxicity profile, as the difference in their corneal permeability was not significant. There was an initial burst release of cyclosporine A in the first 24 h that plateaued over one week. The Tween®-based formulation had a flux of 0.78 µg/cm2/h. The prepared transferosomes demonstrated biocompatibility in the ocular cell line, adequately encapsulated cyclosporine A, ensured the corneal permeability of the enclosed drug, and were stable over the period of investigation of 4 months at −20 °C.

Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2

“…Moreover, amorphization of the drug and perfect encapsulation within the lipid matrix of transferosomes resulted in the disappearance of the drug peak in the curcumin transferosome gel formulation Figure 7D . This observation is consistent with earlier studies that reported identical behaviors of drug-loaded vesicles in gel formulations 76 , 130 where the characteristic peaks of the tested drug products were vanished completely from the thermograms of drug loaded vesicles, indicating drug solubilization in the lipid phase and existence in amorphous state hence, the efficiency and success of the hydrophobic drug encapsulation within lipid matrix of the vesicles.

Figure 7 DSC thermogram of ( A ); Curcumin powder, ( B ) Freeze dried free curcumin gel, ( C ) Freeze dried plain gel, and ( D ) Freeze dried curcumin transferosomes gel.

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Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery

“…Figure E depicts that bulk CsA exhibited a halo diffraction pattern, indicating an amorphous state consistent with the previous literature. , Nanosuspensions only showed diffraction peaks at 19.26 and 23.36°, which were also found in the pattern of TPGS, indicating that the amorphous form of CsA was maintained during the antisolvent precipitation and sonication processes. To further ascertain the physicochemical status of CsA, thermal behaviors of nanosuspensions were studied (Figure F), and it was found that the melting endotherm peak at 133 °C , and the decomposition peak at 228 °C of bulk CsA disappeared or shifted in the thermogram of NS, NS@lipid-PEG/CKC, and NS@lipid/CKC, which all showed an endothermic peak at 41 °C corresponding to the melting point of TPGS. This suggested the interaction between CsA and other ingredients. , …”

Drug-Modified Contact Lenses—Properties, Release Kinetics, and Stability of Active Substances with Particular Emphasis on Cyclosporine A: A Review

“…The research aimed to use transferosomes as potential CyA carriers in ocular delivery. For [122] The study examined the impact of surfactant Brij 98 on CyA release from p-HEMA lenses. The developed models predicted a correlation between an increase in surfactant content (fourfold increase) and a decrease in the percentage of CyA and Brij 98 release over time (twofold).…”