Optimisation of HPMC ophthalmic inserts with sustained release properties as a carrier for thermolabile therapeutics.

A methodology was developed and optimised for the preparation of a new drug delivery system (DDS) with sustained release properties to allow ocular protein delivery and to limit destructive production steps during manufacturing. Elevated temperatures, shear forces and an oxidative environment should be avoided in order to prevent denaturation or oxidation of proteins. An aqueous HPMC solution was prepared using heat and casted into small semi-rod-shaped PVC blisters.

Evaluation of a newly developed HPMC ophthalmic insert with sustained release properties as a carrier for thermolabile therapeutics.

A novel drug delivery system (DDS) with sustained release properties was developed to allow ocular protein delivery. The DDS developed is aimed at overcoming stability issues during preparation such as denaturation of proteins caused by shear forces applied or due to elevated temperatures and air entrapment potentially causing oxidation of the molecule. The rod-shaped HPMC inserts were loaded with lysozyme and several HPMC types were studied and compared.

Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A.

Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 2(4) full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties.

Full factorial design, physicochemical characterisation and biological assessment of cyclosporine A loaded cationic nanoparticles.

Cyclosporine A loaded poly(lactide-co-glycolide) nanoparticles coated with chitosan were prepared using the o/w emulsification solvent evaporation method. A 2(3) full factorial design was used to investigate the effect of 3 preparation parameters on the particle size, polydispersity index, zeta potential and drug release. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the developed nanoparticles.

Development and characterization of Cyclosporine A loaded nanoparticles for ocular drug delivery: Cellular toxicity, uptake, and kinetic studies.

Dry eye syndrome is a common disorder of the tear film caused by decreased tear production or increased evaporation. The objective of this study was to evaluate the potential effectiveness of Cyclosporine A (CsA) nanoparticles (NPs) for the treatment of inflammation of the eye surface. Topical CsA is currently the only and safe pharmacologic treatment of severe dry eye symptoms.

Development of mucoadhesive poly(lactide-co-glycolide) nanoparticles for ocular application.

Pilocarpine loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by solvent evaporation method and coated with various mucoadhesive polymers, in particular chitosan, sodium alginate and poloxamers. The size of chitosan-coated nanoparticles was larger than the size of all the other particles obtained. Their surface charge was changed from negative (-22.

Multi-slice computed tomography with N1177 identifies ruptured atherosclerotic plaques in rabbits.

Rupture-prone and ruptured plaques are characterized by the presence of large numbers of macrophages. N1177 is a contrast agent consisting of iodinated nanoparticles that are selectively phagocytosed by macrophages. The aim of this study was to investigate the effect of N1177 on the CT attenuation of rupture-prone and ruptured plaques in rabbits.

The potential of lipid- and polymer-based drug delivery carriers for eradicating biofilm consortia on device-related nosocomial infections.

Microbial biofilms are microcosm attaching irreversibly to abiotic or biotic surfaces and they are promulgated as congregate of single or multiple populations. The potential of lipid- and polymer-based drug delivery carriers for eradicating biofilm consortia on device-related nosocomial infections is explored in this review. Liposomes-loaded with antimicrobial agents could effectively be applied as anti-biofilm coating to reduce microbial adhesion/colonisation onto medical devices and as drug delivery carriers to biofilm interfaces and in intracellular infection.

Microneedles for transdermal drug delivery: a minireview.

The stratum corneum is the main barrier for transdermal drug transport. It could be bypassed by microneedles, which have a length of a few tens to a few hundreds of microns. They are usually arranged in arrays and can be used in several ways to enhance transdermal drug transport.

Adhesion of PLGA or Eudragit/PLGA nanoparticles to Staphylococcus and Pseudomonas.

The aim of present study was to examine whether cationic Eudragit containing poly(lactide-co-glycolide) (PLGA) nanoparticles can adhere to Pseudomonas aeruginosa and Staphylococcus aureus. In order to prepare fluorescent nanoparticles, fluorescein was covalently coupled to PLGA. Fluorescent PLGA and Eudragit/PLGA nanoparticles were prepared by w/o/w emulsification solvent evaporation.

Ocular drug delivery: nanomedicine applications.

Nanocarriers, such as nanoparticles, liposomes and dendrimers, are used to enhance ocular drug delivery. Easily administered as eye drops, these systems provide a prolonged residence time at the ocular surface after instillation, thus avoiding the clearance mechanisms of the eye. In combination with a controlled drug delivery, it should be possible to develop ocular formulations that provide therapeutic concentrations for a long period of time at the site of action, thereby reducing the dose administered as well as the instillation frequency.

Cytotoxicity of submicron emulsions and solid lipid nanoparticles for dermal application.

The cytotoxicity and physical properties of various submicron O/W emulsions and solid lipid nanoparticles for dermal applications were investigated. Droplet size and zetapotential of submicron emulsions depended on the composition of the cosurfactant blend used. The viability of J774 macrophages, mouse 3T3 fibroblasts and HaCaT keratinocytes was significantly reduced in the presence of stearylamine.

Evaluation of ciprofloxacin-loaded Eudragit RS100 or RL100/PLGA nanoparticles.

The objective of present study was to prepare positively charged ciprofloxacin-loaded nanoparticles providing a controlled release formulation. The particles were prepared by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation, followed by high-pressure homogenisation. Two non-biodegradable positively charged polymers, Eudragit RS100 and RL100, and the biodegradable polymer poly(lactic-co-glycolic acid) or PLGA were used alone or in combination, with varying ratios.

The use of mucoadhesive polymers in ocular drug delivery.

In the present update on mucoadhesive ocular dosage forms, the tremendous advances in the biochemistry of mucins, the development of new polymers, the use of drug complexes and other technological advances are discussed. This review focusses on recent literature regarding mucoadhesive liquid (viscous solutions, particulate systems), semi-solid (hydrogel, in situ gelling system) and solid dosage forms, with special attention to in vivo studies. Gel-forming minitablets and inserts made of thiomers show an interesting potential for future applications in the treatment of ocular diseases.

Effects of roller compaction settings on the preparation of bioadhesive granules and ocular minitablets.

An experimental factorial design was employed to evaluate bioadhesive granules and bioerodible ocular minitablets (6 mg and Psi 2 mm). The purpose of this study was to compare minitablets prepared using roller compacted granules with an optimised minitablet formulation, manufactured on laboratory scale by direct compression. The formulation consisted of drum dried waxy maize starch, Carbopol 974P, and ciprofloxacin in a ratio of 90.

Influence of the homogenisation procedure on the physicochemical properties of PLGA nanoparticles.

Pilocarpine HCl-loaded PLGA nanoparticles were prepared by emulsification solvent evaporation. Three different stabilisers, polyvinylalcohol (PVA), Carbopol and Poloxamer were used, as well as mixtures thereof. The influence of the homogenisation pressure and number of cycles on the properties of nanoparticles were studied.

The influence of the use of viscosifying agents as dispersion media on the drug release properties from PLGA nanoparticles.

Poly(lactide-co-glycolide) nanoparticles incorporating ciprofloxacin HCl were prepared by means of a W/O/W emulsification solvent evaporation method. The physicochemical properties of these particles were evaluated by measuring particle size, zeta potential and drug loading efficiency. Gamma-sterilised nanoparticles were dispersed in different isoviscous polymer solutions, commonly used as vehicles in eye drops.

Ocular bioerodible minitablets as strategy for the management of microbial keratitis.

Purpose: Evaluation in volunteers of ciprofloxacin-containing ocular gelling minitablets with prolonged release properties.

Methods: The irritation potential of ciprofloxacin-containing bioadhesive powder mixtures, used to prepare ocular bioerodible minitablets, was evaluated with a slug mucosal-irritation test. The tear pharmacokinetic profiles of ciprofloxacin were determined in six healthy volunteers after topical administration of a minitablet and a single eye drop in the lower fornix.

Factorial design, physicochemical characterisation and activity of ciprofloxacin-PLGA nanoparticles.

Poly(lactide-co-glycolide) nanoparticles incorporating ciprofloxacin HCl were prepared by means of a W/O/W emulsification solvent evaporation method. The stabiliser selected was poly(vinylalcohol). A 2(4) full factorial design based on four independent variables was used to plan the experiments and the variable parameters were the number of homogenisation cycles, addition of boric acid to the inner water phase containing the drug, ciprofloxacin concentration in the inner water phase and oil:outer water phase ratio.

Determinants of eye drop size.

Ophthalmic solutions are available for multidose or single-dose administration in a wide variety of glass and plastic dropper bottles which deliver drops with a volume between 25 and 70 microl. From a biopharmaceutical and economic point of view, however, smaller volumes of 5 to 15 microl should be instilled. In this review, the technical, pharmaceutical, and therapeutic aspects of eye drop formation and delivery are presented.

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.

Optimisation of carbomer viscous eye drops: an in vitro experimental design approach using rheological techniques.

The optimisation of the in vitro interaction between several poly(acrylic acid) derivatives (Carbopol 1342P NF, Carbopol 974P and Carbopol 980 NF) and mucin was performed by an analysis technique combining oscillatory shear rheology and experimental design in order to improve the formulation of carbomer viscous eye drops.First, standard oscillation procedures were used to characterise the polyacrylic acid and mucin dispersions, and to investigate the influence of several polymer-related factors (concentration, preparation, type of polymer used) on the rheological properties. Second, an experimental plan design was developed to investigate the effect of polymer-related factors on the mucoadhesive indexes (MAI(G') and MAI(G")) which were calculated using the viscoelastic data obtained from polymer/mucin, polymer/tearfluid and mucin/tearfluid mixtures.

The use of xanthan gum in an ophthalmic liquid dosage form: rheological characterization of the interaction with mucin.

The development of an ocular dosage form containing xanthan gum and capable of interacting with mucin in the precorneal area is a challenge. The polymer concentration that can be applied is restricted because of the limited patient acceptability of highly viscous preparations. The precorneal mucin concentration is low and the high ionic strength of the lachrymal fluid forces xanthan gum in an ordered structure, less capable of interacting through heterotypic junctions.