Barrier analysis of periocular drug delivery to the posterior segment.

Periocular administration is a potential way of delivering drugs to their targets in posterior eye segment (vitreous, neural retina, retinal pigment epithelium (RPE), choroid). Purpose of this study was to evaluate the role of the barriers in periocular drug delivery. Permeation of FITC-dextrans and oligonucleotides in the bovine sclera was assessed with and without Pluronic gel in the donor compartment.

Radiosynthesis and assessment of ocular pharmacokinetics of (124)I-labeled chitosan in rabbits using small-animal PET.

Purpose: The polysaccharide chitosan is a unique material for the design of ocular drug-delivery vehicles. The aim of this study was to radiolabel chitosan with iodine-124 ((124)I) for measurement of ocular pharmacokinetics in rabbits using small-animal positron emission tomography (PET).

Procedures: Crl:CHBB (HM) rabbits received one drop (35 µL) of either a formulation containing chitosan (0.

Low molecular weight hyaluronan shielding of DNA/PEI polyplexes facilitates CD44 receptor mediated uptake in human corneal epithelial cells.

Aim: It was the aim of this study to prepare purified DNA/PEI polyplexes, which are coated with hyaluronan to facilitate CD44 receptor mediated uptake of the DNA/PEI polyplex and to reduce unspecific interactions of the complex with negatively charged extracellular matrix components on the ocular surface.

Methods: Hyaluronans of different molecular weights (<10 kDa, 10-30 kDa and 30-50 kDa) were isolated after enzymatic degradation of high molecular weight hyaluronan via ultrafiltration by centrifugation. The influence of the different hyaluronans used for coating on the stability and transfection efficiency of the complexes was evaluated in vitro.

Peribulbar poloxamer for ocular drug delivery.

Purpose: The use of biopolymers in peribulbar injection for controlled drug delivery provides alternative options to eyedrops and intravitreal or surgical methods. Polymerizable biopolymers are especially likely to have a role because of their particular properties. In liquid form, they can be easily injected into the target site and, after polymerization, they provide a prolonged and controlled release of the drug.

Corneal epithelium as a platform for secretion of transgene products after transfection with liposomal gene eyedrops.

Background: The first objective of the study was to evaluate the transfection of corneal epithelium with non-viral vectors to secrete transgene products into the tear fluid and aqueous humor. The second goal was to evaluate the differentiated corneal epithelial cell culture for transfection studies.

Methods: The human corneal epithelial (HCE) cell line was cultured to different stages of differentiation and transfected with complexes of pCMV-SEAP2 with DOTAP/DOPE, DOTAP/DOPE/protamine sulfate (PS) and polyethylenimine (PEI).

Cell culture models of the ocular barriers.

The presence of tight barriers, which regulate the environment of ocular tissues in the anterior and posterior part of the eye, is essential for normal visual function. The development of strategies to overcome these barriers for the targeted ocular delivery of drugs, e.g.

Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation.

The aim of the present study was to evaluate the influence of the degree of modification and the polymer chain length on the mucoadhesive properties and the swelling behavior of thiolated chitosan derivatives obtained via a simple one-step reaction between the polymer and 2-iminothiolane. The conjugates differing in molecular mass of the polymer backbone and in the amount of immobilized thiol groups were compressed into tablets. They were investigated for their mucoadhesive properties on freshly excised porcine mucosa via tensile studies and the rotating cylinder method.

Thiolated chitosans.

The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. So far, three types of thiolated chitosans have been generated: chitosan-cysteine conjugates, chitosan-thioglycolic acid conjugates and chitosan-4-thio-butyl-amidine conjugates. Various properties of chitosan are improved by this immobilization of thiol groups.

Thiolated polymers--thiomers: synthesis and in vitro evaluation of chitosan-2-iminothiolane conjugates.

The aim of this study was to improve the properties of chitosan as excipient in drug delivery systems by the covalent attachment of thiol moieties. This was achieved by the modification of chitosan with 2-iminothiolane. The resulting chitosan-4-thio-butyl-amidine conjugates (chitosan-TBA conjugates) displayed up to 408.

Mucoadhesive ocular insert based on thiolated poly(acrylic acid): development and in vivo evaluation in humans.

The aim of the study was to develop a mucoadhesive ocular insert for the controlled delivery of ophthalmic drugs and to evaluate its efficacy in vivo. The inserts tested were based either on unmodified or thiolated poly(acrylic acid). Water uptake and swelling behavior of the inserts as well as the drug release rates of the model drugs fluorescein and two diclofenac salts with different solubility properties were evaluated in vitro.

In vitro evaluation of the viscoelastic properties of chitosan-thioglycolic acid conjugates.

The aim of this study was to evaluate the viscoelastic properties of chitosan-thioglycolic acid conjugates with different amounts of thiol groups immobilized on the polymer. The modification of chitosan was achieved via the covalent attachment of thioglycolic acid mediated by a carbodiimide. Chitosan-thioglycolic acid conjugates displaying 120, 209 and 439 microM thiol groups per gram of polymer were synthesized.

In vitro evaluation of the permeation enhancing effect of polycarbophil-cysteine conjugates on the cornea of rabbits.

It was the aim of this study to investigate the permeation enhancing effect of thiolated polycarbophil on the cornea of rabbits in vitro. The proposed reaction mechanism involves the opening of the tight junctions in the corneal epithelium. The modification of polycarbophil was achieved via covalent attachment of L-cysteine mediated by a carbodiimide.