Delivery of Riboflavin-5′-Monophosphate Into the Cornea: Can Liposomes Provide Any Enhancement Effects?

Abstract

Keratoconus is a progressive condition caused by the thinning of the cornea, which eventually deforms the front surface of the eye into a cone shape leading to ghosting, multiple images, glare, and several other vision problems. Currently, keratoconus is treated with UV-induced riboflavin (Rb)-mediated collagen cross-linking, which requires a physical removal of the corneal epithelium under topical anesthesia. This study reports the penetration of Rb and its more water-soluble form, riboflavin-5'-monophosphate (RbP), into the bovine cornea ex vivo. Using ex vivo bovine corneal tissues and 0.8 mg/mL drug solutions in phosphate buffer, it was established that RbP penetration into the cornea within 3 h of diffusion experiment was greater (17.3 ± 0.8 μg) compared with Rb (10.4 ± 4.2 μg). In the cornea, RbP was found to convert to Rb, which is mediated with enzymes present in this tissue. Several formulations including the conventional and propylene glycol-containing liposomes with encapsulated RbP have been developed, and their effect on the drug penetration into the bovine cornea was evaluated. Encapsulation of RbP into the liposomes did not provide any statistically significant improvement in the penetration of RbP into the cornea.

Development of Lactoferrin-Loaded Liposomes for the Management of Dry Eye Disease and Ocular Inflammation

“…bLF-LIP obtained had an average size of 85 nm, + 23 mV of ZP, and PI around 0.165, characteristic of a monomodal system, so they are suitable for ocular administration [ 46 ]. The PI is a measure of size distribution, agreeing with the literature, liposomal formulation is considered to be heterogeneous if the value is > 0.3 [ 47 ]. Cationic liposome formulation improves ocular surface adherence since ocular mucosa depicts slightly negative charge over its isoelectric point, thus increasing ocular bioavailability and prevent tear washout, prolonging corneal residence time [ 48 ].…”

“…Owing to their high lipophilicity, the epithelium layer of the cornea, composed of lipid, favoured the release of bLF-LIP and prevents the entry of hydrophilic substances, such as free bLF solution, thus retaining a significant part of the protein in the cornea [ 67 ]. Furthermore, particles below 100 nm, particles with deformable nature and positively charged liposomes could potentially facilitate their permeability and absorption through the corneal membrane, leading to an enhance in all pharmacokinetic parameters [ 31 , 47 ]. Therefore, bLF-LIP may efficiently release bLF to the specified area by delivering bLF slowly across the corneal tissue, which would be helpful for the management of DED and the derived ocular inflammation.…”

Mucoadhesive maleimide-functionalised liposomes for drug delivery to urinary bladder

“…Vesicles showing their zeta potential of less than -30 mV are believed to have excellent colloidal 263 stability and have the reduced number of bilayer membranes due to the electrostatic repulsion between 264 the charges of the same polarity. Furthermore, liposomal formulation with ≤ -30 mV would have higher 265 entrapment capacity because stronger zeta potential contributes to the increase in the unilamellar 266 vesicles (Sou, 2011;Kandzija and Khutoryanskiy, 2017). The physicochemical characteristics of 267 different liposomes are summarised in Table 2.…”

Liposomal Form of the Echinochrome-Carrageenan Complex

“…Many factors influence the encapsulation efficiency (% EE) and loading capacity of liposomes, including the drug/liposome ratio, the lipid composition, the presence of the charge, the method of preparation, and the chemical structure of the drug [ 35 ]. According to the data of Kandzija and Khutoryansky, water-soluble drugs have lower encapsulation in liposomes compared to their lipophilic counterparts [ 36 ]. Our data show that liposomes had the highest encapsulation efficiency related to Ech, which may be due to its hydrophobic nature and being stuck in the lipid bilayers, as was shown for the hydrophobic drug [ 10 , 24 ].…”