John Tsibouklis

The potential for nanoparticle-based drug delivery to the brain: overcoming the blood-brain barrier.

The development of blood–brain barrier (BBB)-targeting technologies is a very active field of research: targeting therapeutic actives to the central nervous system by means of systemic administration means crossing the BBB, and this is now one of the most challenging problems in drug development. The BBB is a unique regulatory system that protects the brain environment by separating it from direct contact with the circulating blood. In doing so, it impedes at the same time the access of a large number of diagnostic and therapeutic agents into the brain parenchyma. One of the possibilities of bypassing this barrier relies on specific properties of nanoparticulate vectors designed to interact with BBB-forming cells at a molecular level, as a result of which the transport of drugs or other molecules (such as nucleic acids, proteins or imaging agents) could be achieved without interfering with the normal function of the brain. This article summarises several recent example applications, presents emerging work and highlights the directions for further developments in this area.

Azo compounds in colon-specific drug delivery

Azo compounds have the potential to act as drug carriers that facilitate the selective release of therapeutic agents to the colon, and also to effect the oral administration of those macromolecular drugs that require colon-specific drug delivery. With some further research-driven refinements, these materials may lead to more efficient treatments for local conditions, such as colonic cancer or inflammatory bowel disease. This article provides an overview of the azo-based systems developed to date, identifies the requirements for an ideal carrier, and highlights the directions for further developments in the field of azo group-facilitated colonic delivery.

Hybrid polymeric hydrogels for ocular drug delivery: nanoparticulate systems from copolymers of acrylic acid-functionalized chitosan and N-isopropylacrylamide or 2-hydroxyethyl methacrylate

Nanoparticulate hybrid polymeric hydrogels (10-70 nm) have been obtained via the radical-induced co-polymerization of acrylic acid-functionalized chitosan with either N-isopropylacrylamide or 2-hydroxyethyl methacrylate, and the materials have been investigated for their ability to act as controlled release vehicles in ophthalmic drug delivery. Studies on the effects of network structure upon swelling properties, adhesiveness to substrates that mimic mucosal surfaces and biodegradability, coupled with in vitro drug release investigations employing ophthalmic drugs with differing aqueous solubilities, have identified nanoparticle compositions for each of the candidate drug molecules. The hybrid nanoparticles combine the temperature sensitivity of N-isopropylacrylamide or the good swelling characteristics of 2-hydroxyethyl methacrylate with the susceptibility of chitosan to lysozyme-induced biodegradation.

Docosanoyl itaconate/1-docosylamine alternate-layer Langmuir–Blodgett films: polymerisation, pyroelectric properties and infrared spectroscopic studies

Langmuir–Blodgett multilayers of an isomeric mixture of an itaconate monoester have been prepared. Multilayers were polymerised via initiation by irradiation with ultraviolet light and the reactions studied by UV–VIS spectrophotometry and gel permeation chromatography. Alternate-layer structures of the itaconate monomer and the corresponding polymer with an aliphatic amine have also been built-up. X-Ray reflectivity experiments have indicated that the bilayer spacing of these films did not change upon polymerisation. An evaluation of the pyroelectric properties of the alternate-layer structures revealed that, although the monomer/amine system possessed a pyroelectric coefficient of 1.4 µC m–2 K–1, polymer/amine films were not pyroelectric. The mechanism responsible for the loss of the pyroelectric activity is discussed on the basis of infrared spectroscopic investigations.

Carborane-based derivatives of delocalised lipophilic cations for boron neutron capture therapy: synthesis and preliminary in vitro evaluation

Aimed towards the development and effective delivery of highly boronated antitumour agents for use in the neutron capture therapy of cancer, closo-carboranyl derivatives of Nile blue and salts of dequalinium, rhodamine-123 and tetraphenyl phosphonium incorporating nido-carborane counterions have been synthesized and characterized. A preliminary in vitro evaluation in human cell lines indicated the propensity of these agents to target tumour cells, and to deliver therapeutically relevant quantities of boron.

Toward drug delivery into the brain: synthesis, characterization, and preliminary in vitro assessment of alkylglyceryl-functionalized chitosan nanoparticles

A series of O-substituted alkylglyceryl chitosans with systematically varied degrees of grafting was prepared through synthetic steps that involved the protection of amino moieties via phthaloylation and employed for the formulation of aqueous nanoparticulate systems that may be capable of delivering drugs to the brain. Dynamic light scattering studies have shown that nanoparticles with physiologically relevant aqueous stabilities may be prepared following the partial quaternization of these alkylglyceryl-modified chitosans. Preliminary in vitro tests using a mouse-brain endothelial cell model have indicated the efficient cellular uptake of these nanoparticles and identified butylglyceryl chitosan and butylglyceryl N,N,N-trimethyl chitosan as promising materials for the formulation of colloidal systems that could act as drug carriers into the brain.

Tricos-22-enoic acid/1-docosylamine alternate-layer Langmuir–Blodgett films: polymerisation, pyroelectric properties and infrared spectroscopic studies

Pyroelectric alternate-layer Langmuir-Blodgett films of tricos-22-enoic acid and 1-docosylamme have been polymerised by ultravoilet irradiation. Partially polymerised films retained a significant proportion of the initial Pyroelectric activity. However, irradiation for long periods of time resulted in decarboxylation and photodesorption, which eventually led to the loss of the pyroelectric response.