Formulations and toxicologic in vivo studies of aqueous cyclosporin A eye drops with cyclodextrin nanoparticles

Johannsdottir, Sunna; Kristinsson, Jóhannes Kári; Fülöp, Zoltán; Ásgrimsdóttir, Guðrún Marta; Stefánsson, Einar; Loftsson, Þorsteinn

doi:10.1016/j.ijpharm.2017.07.044

Cited by 26 publications

(11 citation statements)

References 20 publications

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“…123 Some recent case studies of the CDs in the optimal drug delivery of drugs, proteins, peptides and aptamers are reported in the Table 3. [124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140] CDs can be moulded into various types of formulation for proving ease the drug delivery by diverse routes of administration.…”

Section: An Account Of Recent Advances In Cds For Optimal Drug Deliverymentioning

confidence: 99%

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

2020

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Colloidal nanoparticulate technology has been described in the literature as a versatile drug delivery system. But it possesses some inherent lacunae in their formulation. Cyclodextrins (CDs) have been extensively reported for the solubility enhancement of poorly water-soluble drugs. The CDs can cause intervention in aspects related to nanoparticles (NPs) that include improving drug loading in nano-system, improving stability, site-specific/targeted drug delivery, improving solubility profile and absorption of the drug in nanosystem with consequent improvement in bioavailability, with the possibility of controlled release, safety and efficacy. They find application in for simultaneous diagnosis and therapeutics for better treatment procedures. The current communication is focused on the application of CDs to overcome troubles in nanoparticulate formulation and enhancement of their performance. It also envisages the theranostic aspects of CDs.

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Section: An Account Of Recent Advances In Cds For Optimal Drug Deliverymentioning

confidence: 99%

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

2020

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“…The use of CDs in topical ocular drug formulations has been recently reported to improve the solubilization of various substances including corticosteroids, medications for glaucoma treatment and immunosuppressive agents [ 17 , 22 , 23 ]. In particular, CDs enhance ocular permeability of poorly soluble drugs through the lipophilic corneal epithelial membrane and increase their bioavailability in the anterior chamber [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

et al. 2021

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The purpose of this study was to evaluate the ocular pharmacokinetics, bio-distribution and local tolerability of γ-cyclodextrin (γCD) based irbesartan 1.5% eye drops and candesartan 0.15% eye drops after single and multiple topical administration in rabbit eyes. In this randomized, controlled study, a total number of 59 New Zealand White albino rabbits were consecutively assigned to two study groups. Group 1 (n = 31) received irbesartan 1.5% and group 2 (n = 28) candesartan 0.15% eye drops. In both groups, single dose and multiple administration pharmacokinetic studies were performed. Rabbits were euthanized at five predefined time points after single-dose administration, whereas multiple-dose animals were dosed for 5 days twice-daily and then euthanized 1 h after the last dose administration. Drug concentration was measured by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the retinal tissue, vitreous humor, aqueous humor, corneal tissue and in venous blood samples. Pharmacokinetic parameters including maximal drug concentration (Cmax), time of maximal drug concentration (Tmax), half-life and AUC were calculated. To assess local tolerability, six additional rabbits received 1.5% irbesartan eye drops twice daily in one eye for 28 days. Tolerability was assessed using a modified Draize test and corneal sensibility by Cochet Bonnet esthesiometry. Both γCD based eye drops were rapidly absorbed and distributed in the anterior and posterior ocular tissues. Within 0.5 h after single administration, the Cmax of irbesartan and candesartan in retinal tissue was 251 ± 142 ng/g and 63 ± 39 ng/g, respectively. In the vitreous humor, a Cmax of 14 ± 16 ng/g for irbesartan was reached 0.5 h after instillation while Cmax was below 2 ng/g for candesartan. For multiple dosing, the observed Cmean in retinal tissue was 338 ± 124 ng/g for irbesartan and 36 ± 10 ng/g for candesartan, whereas mean vitreous humor concentrations were 13 ± 5 ng/g and <2 ng/g, respectively. The highest plasma concentrations of both irbesartan (Cmax 5.64 ± 4.08 ng/mL) and candesartan (Cmax 4.32 ± 1.04 ng/mL) were reached 0.5 h (Tmax) after single administration. Local tolerability was favorable with no remarkable differences between the treated and the control eyes. These results indicate that irbesartan and candesartan in γCD based nanoparticle eye drops can be delivered to the retinal tissue of the rabbit’s eye in pharmacologically relevant concentrations. Moreover, safety and tolerability profiles appear to be favorable in the rabbit animal model.

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“…Commercial pharmaceutical ophthalmic products of indocid (indomethacin) and Voltranen Ophtha (Diclofenac sodium) contain HP‐β‐CD and HP‐γ‐CD as solubilizing agent, respectively. in vivo toxicologic studies in rabbits with aqueous ophthalmic drops containing cyclosporin A‐CD nanoparticles have been performed (Jóhannsdóttir et al, ). An in situ antifungal ophthalmic gelling formulation of HP‐β‐CD‐voriconazole complexes was prepared using pluronic polymers and sodium alginate by cold gelation technique.…”

Section: In Drug Delivery Systemsmentioning

confidence: 99%

Cyclodextrin complexes: Perspective from drug delivery and formulation

Jacob

Nair

2018

Drug Development Research

174

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Cyclodextrins (CDs) have been widely investigated as a unique pharmaceutical excipient for past few decades and is still explored for new applications. They are highly versatile oligosaccharides which possess multifunctional characteristics, and are mainly used to improve the physicochemical stability, solubility, dissolution rate, and bioavailability of drugs. Stability constant, factors affecting complexation, techniques to enhance complexation efficiency, the preparation methods for molecular inclusion complexes and release of guest molecules are discussed in brief. In addition, different CD derivatives and their pharmacokinetics are elaborated. Further, the significance of CD complex in aqueous solubility, dissolution and bioavailability, stability, and taste masking is explained. The recent advancement of CDs in developing various drug delivery systems is enlightened. Indeed, the potential of CDs by means of inclusion complex formation have widen the applicability of these materials in various drug delivery systems including ocular, osmotic, mucoadhesive, transdermal, nasal, and targeted delivery systems. Feasibility studies have been performed on the benefit of these cyclic oligomers as nanocarriers, a strategy that can modify the drugs with improved physicochemical properties. Studies also demonstrated the feasibility of CDs to self-assemble in the form of stable nanoaggregates, which may extend the scope of CDs in drug delivery to the continually expanding list of new drug entities.

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Formulations and toxicologic in vivo studies of aqueous cyclosporin A eye drops with cyclodextrin nanoparticles

Cited by 26 publications

References 20 publications

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

Cyclodextrin Based Nanoparticles for Drug Delivery and Theranostics

Bio-Distribution and Pharmacokinetics of Topically Administered γ-Cyclodextrin Based Eye Drops in Rabbits

Cyclodextrin complexes: Perspective from drug delivery and formulation

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