O Felt-Baeyens | PubMed Health

PubMed2006

Biodegradable scleral implants as new triamcinolone acetonide delivery systems.

The goal of this study was to develop ocular scleral implants able to release triamcinolone acetonide (TA) overall several months. Scleral discs were manufactured by a compression-molding method using a new synthetic polymer, poly(methylidene malonate) (PMM2.1.2), as matrix. Implants with good mechanical properties adapted for in vivo implantation have been obtained when using high M(w) PMM2.1.2 (100,000 - 150,000 Da) associated with ethoxylated derivatives of stearic acid (Simulsol) or oligomers of methylidene malonate as plasticizer. After implantation in rabbit eyes, scleral implants showed a good ocular biocompatibility. Indeed, the clinical follow-up and ocular inflammation parameters, such as inflammatory cell number and protein content in aqueous humor, demonstrated that implants were well tolerated and did not provoke abnormal inflammation. Implants were able to release significant concentrations of TA in the vitreous and the sclera throughout 5 weeks.

Absorbable Implants↗

PubMed2005

A novel water-soluble cyclosporine A prodrug: ocular tolerance and in vivo kinetics.

The purpose of this study is to demonstrate that a novel water-soluble prodrug of cyclosporine A (CsA) intended for topical ocular administration, does not induce eye irritation in a rabbit model and is able to generate therapeutic concentrations of CsA in the precorneal area immediately after administration. The eye irritancy of the prodrug and CsA control solution was assessed by the Draize test and by confocal laser ophthalmoscopy (CLSO). Residence time and tear concentrations of prodrug and CsA in the rabbit eye were assessed by HPLC. The Draize test showed an excellent tolerance for the prodrug solution while the reference CsA oil solution induced lachrymation and irritation. The CLSO-measured corneal lesions, subsequent to treatment with the prodrug and reference solutions, were 3% and 9%, respectively. The prodrug transformed rapidly, leading to relatively stable CsA concentrations in tears with a maximal concentration of 94 microg ml(-1) over the observation period. This study demonstrated that the prodrug solution was well tolerated and that clinically significant CsA tear concentrations were achieved. UNIL088 is a promising molecule in the treatment of immune-related disorders of the eye.

Administration, Topical↗

PubMed2005

Conversion of cyclosporine A prodrugs in human tears vs rabbits tears.

The aim of this study was to evaluate the rate and mechanism of conversion of two water-soluble prodrugs of cyclosporine A (CsA) intended for topical delivery to the eye. The new molecules were designed according to the double prodrug concept: a solubilizing moiety was grafted onto CsA via an ester function, which could be hydrolysed via a two-step process (enzymatic and chemical). Prodrug solutions were prepared extemporaneously in an isotonic and neutral aqueous medium compatible with ophthalmic use. The rates of conversion into the parent molecule were determined by incubating the prodrugs in fresh rabbit or human tears or in a phosphate buffer solution (PBS) at pH 7.4. Both prodrugs were converted into CsA within the first minute in the presence of rabbit tears with rate constants of k=5.9x10(-3)min(-1) and k=3.8x10(-3)min(-1), respectively, for UNIL088 and UNIL089, whereas chemical conversion in PBS was negligible (k=0.5x10(-3)min(-1) for both molecules). Incubation of UNIL088 in human tears showed a significantly high conversion rate. It is concluded that the developed double prodrugs underwent a bioconversion in physiological media and thus represent promising candidates for topical delivery of CsA to the eye.

Animals↗

PubMed2004

Pseudo-thermosetting chitosan hydrogels for biomedical application.

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Biomedical Technology↗

PubMed2004

Pseudo-thermosetting chitosan hydrogels for biomedical application.

To prepare transparent chitosan/beta-glycerophosphate (betaGP) pseudo-thermosetting hydrogels, the deacetylation degree (DD) of chitosan has been modified by reacetylation with acetic anhydride. Two methods (I and II) of reacetylation have been compared and have shown that the use of previously filtered chitosan, dilution of acetic anhydride and reduction of temperature in method II improves efficiency and reproducibility. Chitosans with DD ranging from 35.0 to 83.2% have been prepared according to method II under homogeneous and non-homogeneous reacetylation conditions and the turbidity of chitosan/betaGP hydrogels containing homogeneously or non-homogeneously reacetylated chitosan has been investigated. Turbidity is shown to be modulated by the DD of chitosan and by the homogeneity of the medium during reacetylation, which influences the distribution mode of the chitosan monomers. The preparation of transparent chitosan/betaGP hydrogels requires a homogeneously reacetylated chitosan with a DD between 35 and 50%.

Biomedical Technology↗

PubMed2003

Cyclosporine A delivery to the eye: a pharmaceutical challenge.

Systemic administration of cyclosporine A (CsA) is commonly used in the treatment of local ophthalmic conditions involving cytokines, such as corneal graft rejection, autoimmune uveitis and dry eye syndrome. Local administration is expected to avoid the various side effects associated with systemic delivery. However, the currently available systems using oils to deliver CsA topically are poorly tolerated and provide a low bioavailability. These difficulties may be overcome through formulations aimed at improving CsA water solubility (e.g. cyclodextrins), or those designed to facilitate tissue drug penetration using penetration enhancers. The use of colloidal carriers (micelles, emulsions, liposomes and nanoparticles) as well as the approach using hydrosoluble prodrugs of CsA have shown promising results. Solid devices such as shields and particles of collagen have been investigated to enhance retention time on the eye surface. Some of these topical formulations have shown efficacy in the treatment of extraocular diseases but were inefficient at reaching intraocular targets. Microspheres, implants and liposomes have been developed to be directly administered subconjunctivally or intravitreally in order to enhance CsA concentration in the vitreous. Although progress has been made, there is still room for improvement in CsA ocular application, as none of these formulations is ideal.

Administration, Topical↗

PubMed2002

Clinical evaluation of bioadhesive ophthalmic drug inserts (BODI) for the treatment of external ocular infections in dogs.

In the case of external ocular diseases such as conjunctivitis, keratoconjunctivitis sicca (KCS) and superficial corneal ulcers, topical administration of eyedrops containing an antibacterial agent is often prescribed. Numerous daily instillations of eyedrops over several days are required for successful treatment, often leading to bad compliance. In addition, the reflex lachrymation following instillation promotes rapid elimination of the drug from the corneal surface. To overcome the disadvantage of repeated instillations, a soluble bioadhesive ophthalmic drug insert (BODI) to be placed in the lower cul de sac of the eye was developed. The clinical efficacy, after deposition of one insert and a classical eyedrop treatment (Tiacil), Virbac Laboratories), was investigated in dogs presenting conjunctivitis, superficial corneal ulcer or keratoconjunctivitis sicca (KCS). Similar total clinical recovery results were obtained after 3 and 7 days for both treatments. BODI can therefore advantageously be prescribed for the treatment of external ophthalmic diseases, by reducing the treatment to a single application and therefore improving compliance compared to classical eyedrop treatment.

Adhesives↗