Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs

Mazet, Roseline; Choisnard, Luc; Levilly, Delphine; Wouessidjewe, Denis; Gèze, Annabelle

doi:10.3390/pharmaceutics10040249

Cited by 17 publications

(10 citation statements)

References 32 publications

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“…The HPLC method was adopted as reported by Mazet et al and further validated. [17] The quantitative determination was carried out by HPLC (Agilent 1290, Agilent Technologies, USA) using reverse phase DikMa C18 column (50 × 4.6 mm, 5 µm) and a mobile phase composed of methanol and water (70:30, v/v) at a flow rate of 0.8 mL min −1 . The column temperature was at 25 °C, and chromatograms were obtained using a refractive index detector at a wavelength of 240 nm.…”

Section: Hplc and Lc-ms/ms Methods Validationmentioning

confidence: 99%

Facile Synthesis and Size Control of 2D Cyclodextrin‐Based Metal–Organic Frameworks Nanosheet for Topical Drug Delivery

Bello

Yang

Wang

et al. 2020

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carrier system is delivering the active ingredient(s) to the target site of action in a safe, effective and efficient way to elicit its pharmacological effect. [1,2] Precisely, the drug should arrive at the disease site at the right time in a controlled manner. Topical eye formulations are the most convenient and accepted ocular delivery systems for treating eye diseases accounting for up to 90% of ophthalmic medicines. [3] However, only 5% of the instilled dose penetrates into the deeper ocular tissues while the larger percentage gets lost through rapid eye blinking, tear turnover, and nasolacrimal drainage. Hence, making it extremely difficult to achieve therapeutic drug concentration following topical eye instillation. [4] To overcome these challenges, numerous works have been reported in the literature and various strategies implemented to improve ocular bioavailability and retention time. [5-7] Several formulations and novel carrier systems have been designed, for example, in situ forming gel system, [8,9] microemulsions, [10,11] and liposomes, [12,13] which are specifically designed to achieve favorable residence time and sustained drug release. Though the use of these technologies has opened the door for more specific and targeted delivery systems, the number of the novel ocular products entering into the market is very slow In this work, a 2D nanosheet (NS) of γ-cyclodextrin (CD)-based metalorganic frameworks (MOFs) is synthesized through a facile green chemistry approach. NS-MOF carrier is constructed using a water system in a simple one-pot reaction involving CD and potassium carbonate. Particle size optimization is achieved by adjusting the reaction temperature and the introduction of crystal growth suppressor (appropriate proportion of acetone). The NS-MOF stability in aqueous medium is improved by polymerization reaction of crosslinked CD-MOF (CL-CD-MOF) without blocking its cavity for drug loading. The effects of particle geometry and size of nanoporous materials on their pharmacokinetics during drug delivery are compared between the sheetlike DXM@CL-NS-MOF and 3D-cubic-shaped DXM@CL-CD-MOF loaded with the same quantity of dexamethasone (DXM). The bioefficiency of these carriers in tear fluids and aqueous humors to deliver DXM is investigated in vivo. The results demonstrate that the 2D-nanosheet particles significantly improve precorneal residence time and intraocular bioavailability over the commercial Maxidex (0.1% dexamethasone) and its 3D-cubes counterpart of similar chemical composition. It suggests that the geometry of a carrier play a significant role in the biodistribution, and the carrier of CL-NS-MOF is a good candidate for ocular drug delivery.

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Section: Hplc and Lc-ms/ms Methods Validationmentioning

confidence: 99%

Facile Synthesis and Size Control of 2D Cyclodextrin‐Based Metal–Organic Frameworks Nanosheet for Topical Drug Delivery

Bello

Yang

Wang

et al. 2020

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“…The composition of optimized mixed Gels A and B were obtained by means of experimental design, as previously described [ 7 ] ( Table 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…The drug quantification methodology was adapted from that previously reported [ 7 , 12 ] and validated in DXMa concentrations according to ICH Q2 (R1) guidelines in order to evaluate specificity, linearity, repeatability, intermediate fidelity, and limit of detection (LOD) and limit of quantification (LOQ) [ 13 ]. Quantitative determination were performed on a reversed-phase, high-performance liquid chromatographic (HPLC) component system LC 2010 AHT (SHIMADZU, Kyoto, Japan) consisting of a pump with degasser, an autosampler, a UV–VIS detector, and a column XTERRA ® MS C8, 5 µm particles, and 150 × 4.6 mm with a C8 cartridge.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, for the topical administration of DXMa into the eyes, we previously developed, by means of experimental designs, two optimized formulations based on HPβCD or HPγCD/DXMa solutions and marketed gels, with the aim of increasing DXMa bioavailability and reducing instillation frequency. HPβCD or HPγCD have considerably enhanced DXMa solubility in water, 500, and 1550-fold [ 7 ]. CELLUVISC ® (sodium carboxymethylcellulose) and VISMED ® (sodium hyaluronate) have both been used as an artificial tear in order to stabilize the tear film on the ocular surface [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

et al. 2020

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We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa’s ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate in vitro, ex vivo, and in vivo their safety, biopermanence, and transcorneal permeation. Gels A and B are Newtonian fluids and display a viscosity of 13.2 mPa.s and 18.6 mPa.s, respectively, which increases their ocular retention, according to the in vivo biopermanence study by PET/CT. These hydrogels could act as corneal absorption promoters as they allow a higher transcorneal permeation of DXMa through porcine excised cornea, compared to DEXAFREE® and MAXIDEX®. Cytotoxicity assays showed no cytotoxic effects on human primary corneal epithelial cells (HCE). Furthermore, Gel B is clearly safe for the eye, but the effect of Gel A on the human eye cannot be predicted. Both gels were also stable 12 months at 25 °C after sterilization by filtration. These results demonstrate that the developed formulations present a high potential for the topical ocular administration of dexamethasone acetate.

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“…Ethylene diamine–β-cyclodextrin encapsulation could hugely promote corneal curcumin delivery. On the other hand, Mazet et al [ 59 ] explored the effect of mixing dexamethasone with cyclodextrin to improve the aqueous solubility of curcumin. Hydroxypropyl-β-cyclodextrins and hydroxypropyl-γ-cyclodextrins were combined with a marketed mucoadhesive gel for topical administration.…”

Section: Nanomedicine For Eye Diseasesmentioning

confidence: 99%

Therapies Based on Nanoparticles for Eye Drug Delivery

et al. 2020

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Eye drug delivery, particularly to the retina, is a technical hurdle that needs to be solved and represents an ongoing current important medical field. Posterior segment eye diseases are a major cause of visual impairment worldwide. Age-related macular degeneration, glaucoma, and diabetic retinopathy are the major causes of blindness. To achieve efficient drug delivery and drug retention time in the posterior segment of the eye, novel delivery systems based on nanoparticles have been developed in the last few years. Nowadays, liposomes represent the most utilized nanoparticles for eye drug delivery and, recently, a broad spectrum of diverse nanoparticles continue to emerge with special characteristics representing ideal candidates for eye drug delivery.

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Investigation of Combined Cyclodextrin and Hydrogel Formulation for Ocular Delivery of Dexamethasone Acetate by Means of Experimental Designs

Cited by 17 publications

References 32 publications

Facile Synthesis and Size Control of 2D Cyclodextrin‐Based Metal–Organic Frameworks Nanosheet for Topical Drug Delivery

Facile Synthesis and Size Control of 2D Cyclodextrin‐Based Metal–Organic Frameworks Nanosheet for Topical Drug Delivery

Biopharmaceutical Assessment of Dexamethasone Acetate-Based Hydrogels Combining Hydroxypropyl Cyclodextrins and Polysaccharides for Ocular Delivery

Therapies Based on Nanoparticles for Eye Drug Delivery

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