Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction

Boosting transcorneal permeability and pharmacological activity of drug poses a great challenge in the field of ocular drug delivery.In the present study,we propose a drug-peptide supramolecular hydrogel based on anti-inflammatory drug,dexamethasone(Dex),and Arg-Gly-Asp(RGD)motif for boosting transcorneal permeability and pharmacological activity via the ligand-receptor interaction.The drug-peptide(Dex-SA-RGD/RGE)supramolecular hydrogel comprised of uniform nanotube architecture formed spontaneously in phosphate buffered saline(PBS,pH=7.4)without external stimuli.Upon storage at 4℃,25℃,and 37℃ for 70 days,Dex-SA-RGD in hydrogel did not undergo significant hydrolysis,suggesting great long-term stability.In comparison to Dex-SA-RGE,Dex-SA-RGD exhibited a more potent in vitro anti-inflammatory efficacy in lipopolysaccharide(LPS)-activated RAW 264.7 macrophages via the inhibition of nuclear factorкB(NF-κB)signal pathway.More importantly,using drug-peptide supramolecular hydrogel labeled with 7-nitro-2,1,3-benzoxadiazole(NBD),the Dex-SA-K(NBD)RGD showed increased performance in terms of integrin targeting and cellular uptake compared to Dex-SA-K(NBD)RGE,as revealed by cellular uptake assay.On topical instillation in rabbit’s eye,the proposed Dex-SA-K(NBD)RGD could effectively enhance the transcorneal distribution and permeability with respect to the Dex-SA-K(NBD)RGE.Overall,our findings demonstrate the performance of the ligand-receptor interaction for boosting transcorneal permeability and pharmacological activity of drug.

Method Optimization and Application Extension of Bovine Corneal Opacity and Permeability Assay

This paper systematically summarizes the improvements in bovine corneal opacity and permeability assay(BCOP),an alternative method of eye irritation test,further explores the usage mode of combinatorial methods with BCOP at the core module,introduces the application of each single method and their combination in the assessment of pesticides,plant extracts,medical devices and medicines.By optimizing traditional methods,the alternative method is more scientific and individually applicable.

Ocular prodrugs: Attributes and challenges

Ocular drug delivery is one of the most attention-grabbing and challenging endeavors among the numerous existing drug delivery systems.From a drug delivery point of view,eye is an intricate organ to investigate and explore.In spite of many limitations,advancements have been made with the intention of improving the residence time or permeation of the drug in the ocular region.Poor bioavailability of topically administered drugs is the major issue pertaining to ocular drug delivery.Several efforts have been made towards improving precorneal residence time and corneal penetration,e.g.iontophoresis,prodrugs and ionpairing,etc.Prodrug approach(chemical approach)has been explored by the formulation scientists to optimize the physicochemical and biochemical properties of drug molecules for improving ocular bioavailability.Formulation of ocular prodrugs is a challenging task as they should exhibit optimum chemical stability as well as enzymatic liability so that they are converted into parent drug after administration at the desired pace.This review will encompass the concept of derivatization and recent academic and industrial advancements in the field of ocular prodrugs.The progression in prodrug designing holds a potential future for ophthalmic drug delivery.

iRGD decorated liposomes:A novel actively penetrating topical ocular drug delivery strategy

Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.

Ability of Mn2＋ to Permeate the Eye and Availability of Manganese-enhanced Magnetic Resonance Imaging for Visual Pathway Imaging via Topical Administration

Background： Manganese-enhanced magnetic resonance imaging （MEMR1） for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn2＋ to understand the applicability of MEMR1. Methods： Forty New Zealand rabbits were divided into 0.05 mool/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group （n ： 10 in each group）. Each group was i-hrther subdivided into epithelium-removed and epithelium-intact subgroups （n = 5 in each subgroup）. Rabbits were given 8 drops of MnCl2 in 5 min intervals. The Mn2＋ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn2＋ was evaluated with corneal imaging and pathology slices. Results： Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn2＋ concentration times. The intraocular Mn2＋ concentration increased with the concentration gradients ofMn2＋ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved ill the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn2. were 5087 ~ 666 ng/ml, 22920 ± 1188 ng/ml ill the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions： The corneal epithelium is a barrier to Mn2＋, and the iris and lens septum might be another intraocular banier to the permeation of Mn2＋. An elevated Mn2＋ concentration contributes to the increased permeation of Mn2＋, higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn2＋ concentration in the vitreous body.