Formulation of olopatadine hydrochloride viscous eye drops – physicochemical, biopharmaceutical and efficacy assessment using in vitro and in vivo approaches

Račić, Andjelka; Čalija, Bojan; Milić, Jela; Dukovski, Bisera Jurišić; Lovrić, Jasmina; Dobričić, Vladimir; Micov, Ana; Vuković, Marko; Stepanović-Petrović, Radica; Krajišnik, Danina

doi:10.1016/j.ejps.2021.105906

Cited by 12 publications

(11 citation statements)

References 52 publications

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“…Higher values of the permeation coefficient (P app ) for the formulations containing chitosan were observed both on Model I (35.1 × 10 −7 cm/s) and on Model II (5.5 × 10 −7 cm/s). These results represent another confirmation that the action of chitosan as a penetration enhancer is based on different mechanisms for the reversible disruption of tight junctions between epithelial cells, such as the interaction with cell membrane phospholipids, as mentioned above [ 154 ].…”

Section: Characterization Of Mucoadhesive Ophthalmic Preparationssupporting

confidence: 72%

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Račić

Krajišnik

2023

Pharmaceutics

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Dry eye syndrome and allergic conjunctivitis are the most common inflammatory disorders of the eye surface. Although eye drops are the most usual prescribed dosage form, they are characterized by low ocular availability due to numerous barrier mechanisms of the eye. The use of biopolymers in liquid ophthalmic preparations has numerous advantages, such as increasing the viscosity of the tear film, exhibiting bioadhesive properties, and resisting the drainage system, leading to prolonged retention of the preparation at the site of application, and improvement of the therapeutic effect. Some mucoadhesive polymers are multifunctional excipients, so they act by different mechanisms on increasing the permeability of the cornea. Additionally, many hydrophilic biopolymers can also represent the active substances in artificial tear preparations, due to their lubrication and moisturizing effect. With the modification of conventional ophthalmic preparations, there is a need for development of new methods for their characterization. Numerous methods for the assessment of mucoadhesiveness have been suggested by the literature. This review gives an overview related to the development of mucoadhesive liquid ophthalmic formulations for the treatment of dry eye and allergic conditions.

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Section: Characterization Of Mucoadhesive Ophthalmic Preparationssupporting

confidence: 72%

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Račić

Krajišnik

2023

Pharmaceutics

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“…The PAMPA experiment is widely used as an in vitro model for evaluating membrane permeability and transcellular permeation [ 26 , 27 , 28 , 29 , 30 ]. As shown in Figure 5 , compared with the free RAPA solution, the RAPA-NM exhibited a strong permeability potential.…”

Section: Resultsmentioning

confidence: 99%

“…The parallel artificial membrane permeability assay (PAMPA), which enables fast evaluation of the ability of formulations to permeate membranes by passive diffusion, is applied to determine membrane and transcellular permeation of potential drugs. This membrane permeation has also indicated the potential of improved in vivo corneal permeation [ 26 , 27 ]. The PAMPA experiment was performed as previously reported [ 28 , 29 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

Characterization and Evaluation of Rapamycin-Loaded Nano-Micelle Ophthalmic Solution

Zhang

Wei

et al. 2023

JFB

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Rapamycin-loaded nano-micelle ophthalmic solution (RAPA-NM) offers a promising application for preventing corneal allograft rejection; however, RAPA-NM has not yet been fully characterized. This study aimed to evaluate the physicochemical properties, biocompatibility, and underlying mechanism of RAPA-NM in inhibiting corneal allograft rejection. An optimized RAPA-NM was successfully prepared using a polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol (PVCL-PVA-PEG) graft copolymer as the excipient at a PVCL-PVA-PEG/RAPA weight ratio of 18:1. This formulation exhibited high encapsulation efficiency (99.25 ± 0.55%), small micelle size (64.42 ± 1.18 nm), uniform size distribution (polydispersity index = 0.076 ± 0.016), and a zeta potential of 1.67 ± 0.93 mV. The storage stability test showed that RAPA-NM could be stored steadily for 12 weeks. RAPA-NM also displayed satisfactory cytocompatibility and high membrane permeability. Moreover, topical administration of RAPA-NM could effectively prevent corneal allograft rejection. Mechanistically, a transcriptomic analysis revealed that several immune- and inflammation-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the downregulated genes in the RAPA-NM-treated allografts compared with the rejected allogenic corneal grafts. Taken together, these findings highlight the potential of RAPA-NM in treating corneal allograft rejection and other ocular inflammatory diseases.

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“…Ophthalmic formulations should have the pH of the lacrimal fluid, or a pH within the range of the ocular comfort range, in order to ensure a good tolerance [58,59]. The ocular pH ranges from 6.6 to 7.8; it is reported that a pH value of an ocular preparation ranged outside 5.0-8.5 causes extra lachrymation and decreases the ocular residence time [60]. Our formulations showed pH values within the ocular tolerance range, from 7.1 to 7.5 (Table 5).…”

Section: Discussionmentioning

confidence: 99%

mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation

et al. 2021

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The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated in vitro in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (w/v) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy.

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Formulation of olopatadine hydrochloride viscous eye drops – physicochemical, biopharmaceutical and efficacy assessment using in vitro and in vivo approaches

Cited by 12 publications

References 52 publications

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Biopolymers in Mucoadhesive Eye Drops for Treatment of Dry Eye and Allergic Conditions: Application and Perspectives

Characterization and Evaluation of Rapamycin-Loaded Nano-Micelle Ophthalmic Solution

mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation

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