Research Annick Ludwig

Abstract

In the research group Pharmaceutical Technology and Biopharmacy a new method of preparation for ocular dosage forms loaded with peptides and/or proteins has been developed. In this proof-of-concept study, product characteristics and process parameters from the invention will be optimized. The physico-chemical characteristics of the intermediate product and final product from the innovative technological process are evaluated together with optimization of the mixing conditions. The data are needed for submission of a patent with clear defined and specified claims.

Researcher(s)

• Promoter: Ludwig Annick
• Co-promoter: Weyenberg Wim

Research team(s)

Project type(s)

• Research Project

Abstract

Several ocular drug delivery concepts will be developed, characterized in vitro and ex vivo and evaluated in vivo. First the peptide cyclosporine is selected for the development of the concepts. Afterwards, the most promising formulation will be further developed for retinal disorders with a specific peptide.

Researcher(s)

• Promoter: Ludwig Annick
• Co-promoter: Weyenberg Wim

Research team(s)

Project type(s)

• Research Project

Abstract

The scientific aim of the research consortium is to try to understand why some nanocarrriers loaded with biological active molecules (e.g. proteins, antisense oligonucleotides, RNAi, plasmid DNA) are successful and elicit a biological effect in certain cells but fail in other cell structures. It is of fundamental importance to gain insights in these topics. But this is only possible when the problems are tackled with a multidisciplinar team from different prospectives (e.g; biological, pharmaceutical, physicochemical, biophysical, ...)

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The research consists of the formulation and optimalisation of colloidal carriers (liposomes and nanoparticles) in order to target leishmania parasites in the host cells with a broad spectrum and potent saponine. The influence of the technological parameters of the preparation procedure on the physicochemical properties and the endocytosis of the carriers will be investigated. The therapeutic effect in vitro and in vivo will be evaluated.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Shunmugaperumal Tamilvanan

Research team(s)

Project type(s)

• Research Project

Abstract

PX-6518 is a triterpene saponin with a broad-spectrum antileishmania action. Its mode-of-action is still unknown and in vitro and in vivo research is planned to investigate 1/ compound-induced structural changes (histology, EM) of the different parasite stages, 2/ relation between selective accumulation into the phagolysosome and antileishmania activity and 3/ pharmacodynamics and toxicity in the visceral Leishmania hamster model (histopathology, serum biochemistry).

Researcher(s)

• Promoter: Maes Louis
• Co-promoter: Ludwig Annick

Research team(s)

• Laboratory for Microbiology, Parasitology and Hygiene (LMPH)

Project type(s)

• Research Project

Abstract

The aim of the project is to optimise the therapeutic activity of PLGA nanoparticles loaded with ciprofloxacin for the treatment of outer eye infections. I) The nanoparticles will be coated with bioadhesive polymers to improve the interaction with the mucus layer of the tear film in order to extend the residence time at the eye surface. The targeting to different rnicroorganisms will be realised by using cationic polymers. The physical characteristics of the prepared nanoparticles will be determined. 2) The antimicrobial activity of ciprofloxacin loaded and coated PLGA nanoparticles against Pseudomonas aeruginosa, Staphylococcus aureus and Chlamydia trachoma tis will be evaluated. Herewith, the effect of coating on the drug release kinetics and the antimicrobial activity will be studied. 3) The interaction of the nanoparticles with the previously mentioned test microorganisms m culture medium, embedded in biofilrns or located intracellular will be determined.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

To improve the bioavailability of ophthalmic drugs biocompatible and biodegradable colloidal carriers with sustained release will be developed and compare to bioadhesive minitablets. The formulation of PLGA nano or microparticles will be optimised by using factorial design in order to gain insights in the various parameters influencing the physical properties of the particles prepared. Particles will be characterized by measuring the size, zetapotential, drug load and release rate before and after freeze-drying and sterilisation. Moreover the external and internal structures of the particles will be examined. Afterwards the muco or bioadhesion of the carrier will be improved by coating of the particles with (cationic) polymers in order to lengthen the precorneal residence time. Finally from the most promising preparations the in vivo tolerance and release rate from (coated) PLGA particles and minitablets will be investigated.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Dillen Kathleen

Research team(s)

Project type(s)

• Research Project

Abstract

Bioerodible sterilised minitablets (6 mg and diameter 2 mm) used as ocular drug delivery system, will be evaluated in humans. First of all, a clinical study comparing conventional eye drops and optimised minitablets containing ciprofloxacin (3%, w/w) will be performed in healthy volunteers to prove the effectiveness of the minitablet for sustained ocular delivery of ciprofloxacin. Secondly, after in vitro screening of new formulations for sustained release over a longer period of time, an in vivo evaluation of minitablets composed of the formulation with the required sustained release properties and containing fluorescein will be performed in healthy volunteers. A fluorophotometer will be used to measure the tearfilm-cornea concentrations of fluorescein at regular time intervals in a non-invasive way. Finally, if the in vivo study with fluorescein indicates the suitability of the minitablets for obtaining sustained release for a longer period of time, this formulation will be selected to prepare minitablets containing vancomycin and gentamicin and its physicochemical and technological properties will be evaluated in vitro. Consequently these minitablets will be evaluated in the healthy eye of hospitalised patients treated with fortified eye drops for bacterial keratitis. The tear concentrations of the drugs in both eyes will be determined by a validated HPLC method.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

An interesting strategy to increase the bioavailability of ophthalmic drugs is the development of a sterile, bioadhesive minitablet. The minitablets consist of biocompatible, hydrophilic polymers, which form after hydratation by lacrimal fluid a gel. The drug molecules diffuse slowly out of the gel and exert their therapeutic effect at the surface of the eye or after absorption into the eye structures. The influence of the composition of the minitablets, their mode of preparation (direct compression or dry granulation), compression forces used during tabletting and the sterilisation (gamma radiation) on the physical characteristics of the minitablets (friability, tensile strength, swelling behaviour) and the release of the active drug molecule will be examined. The influence of the shelf life conditions (temperature and relative humidity) on the physicochemical properties of the minitablets will be evaluated.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Bozdag Pehlivan Sibel

Research team(s)

Project type(s)

• Research Project

Abstract

To improve the bioavailability of ophthalmic drugs biocompatible and biodegradable colloidal carriers with sustained release will be developed and compare to bioadhesive minitablets. The formulation of PLGA nano or microparticles will be optimised by using factorial design in order to gain insights in the various parameters influencing the physical properties of the particles prepared. Particles will be characterized by measuring the size, zetapotential, drug load and release rate before and after freeze-drying and sterilisation. Moreover the external and internal structures of the particles will be examined. Afterwards the muco or bioadhesion of the carrier will be improved by coating of the particles with (cationic) polymers in order to lengthen the precorneal residence time. Finally from the most promising preparations the in vivo tolerance and release rate from (coated) PLGA particles and minitablets will be investigated.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Dillen Kathleen

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the study is the optimisation of the formulation, the development of the assay method and the evaluation of the stability under different conditions of following preparations: -chlorhexedine hydroalcoholic solution -clindamycin phosphate hydroalcoholic solution

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the study is the optimalisation of the formulation, physical characterisation and the evaluation of the stability under different conditions of following preparations: Nasal suspension with triamcinolonacetonide Suppositories containing collargol Ointment containing isosorbidedinitrate

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The goal of the research project is the optimalisation of the formulation of muco/bioadhesive colloidal carrier systems in order to improve the therapeutic effect of ocular medication. Several parameters influencing the physicochemical properties of PLGA and gelatin nanoparticles and the drugload efficiency (e.g. concentration of compounds; use of stabilisers; homogenisationpressure; coating of or addition of muco/bioadhesive polymers) will be studied using factorial design. From the analyses of the results obtained optimalisation of the formualtion will be realised. The physicochemical characteristics of the nanoparticles prepared namely particle size and polydispersity, zetapotential, surface structure, bioadhesion will be evaluated. The release kinetics of model drugs will be performed in vitro.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Yoncheva Krassimira

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the research project is the formulation of colloidal carrier systems and the study of the parameters influencing the physical properties of the nanoparticles, the stability of the preparaion and the release of model drugs from the nanoparticles prepared. To formulate the carrier systems biocompatible and biodegradable compounds will be employed such as polysaccharides, proteins, phospholipids and polyesters. Besides the classical solvent evaporation and precipitation methods, preparations without organic solvents but using high homogenisation pressures at the temperature required will be performed. Coating of the colloidal particles with bioadhesive polymers could be applied to improve the residence time at the eye surface. The various parameters which could influence the physical properties of the carriers such as the charge and chainlength of the polymers, concentration ratio of the various compounds, addition of excipients, pressure and temperature will be evaluated by means of factorial design. The characterisation of the carrier sytems prepared includes the measurement of the mean particle size and polydispersity, zetapotential, drug loading efficiency. Ocular dosage forms must be sterile, therefore the stability during autoclaving will be examined or the validation of an aseptic preparation method will be performed. The stability of the preparations during storage under various conditions will be evaluated. The in vitro release of model drugs from stable carrier systems will be measured under standard conditions, which simulate the in vivo situation. The influence of tear composition (normal and pathologic) will be studied.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is to develop and characterize carrier systems made of bio-compatible polymers. To improve the bioavailability of ophthalmic drugs, combination of following mechanisme will be used = muco- or/and bioadhesion, endocytosis of the carrier and penetration enhancing of the drug.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Vandervoort Jo

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the research project is to develop biocompatible, topical colloidal carrier systems, which due to their muco- or bioadhesive properties increase the therapeutic efficacy of the medication applied. Phospholipids and polysaccharides were choosen in present study to prepare nanoparticles, because classical solvent evaporation and precipitation methods ernploy organic solvents , which are difficult to remmove completely. The carrier sytems will be prepare at high pressure and required temperature. To increase the residence time at the eye surface the nanoparticles will be coated or mixed with bioadhesive polymers.The various párameters influencing the physicochemical properties of the nanoparticles and the drug loading.effiency such as concentration ratio of the compounds used, charge and chainlength of the polymers, homogenisation pressure and temperature will be evaluated using factorial design. The following characteristics of the nanoparticles prepared will be measured: mean particle size and polydispersity , zetapotential, amount of drug encapsulated. Bioadhesion will be evaluated by means of rheological methods.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is to develop and characterize carrier systems made of bio-compatible polymers. To improve the bioavailability of ophthalmic drugs, combination of following mechanisme will be used = muco- or/and bioadhesion, endocytosis of the carrier and penetration enhancing of the drug.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Vandervoort Jo

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is to develop and characterize carrier systems made of bio-compatible polymers. To improve the bioavailability of ophthalmic drugs, combination of following mechanisme will be used = muco- or/and bioadhesion, endocytosis of the carrier and penetration enhancing of the drug.

Researcher(s)

• Promoter: Ludwig Annick
• Fellow: Vandervoort Jo

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is the development of bioadhesive dosage forms improving the bioavailability of drugs. Characterization (rheological behaviour and bio adhesion) and selection of promising polymers for the formulation of carriersystems will be performed. Bioavailability studies ex vivo and in vivo will be carry out.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

The aim of the project is the development of parenteral for ulations of halofantrine with improved bioavailability. Preparation and physical characterization of various emulsions containing antimalaria drugs will be performed. The influence of the composition, especially the surfactants used, on the therapeutic efficacy of the emulsions will be studied on in vivo animal models.

Researcher(s)

• Promoter: Ludwig Annick

Research team(s)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Van Ooteghem Marcus
• Co-promoter: Ludwig Annick
• Co-promoter: Tassignon Marie-Jose

Research team(s)

Project type(s)

• Research Project