Gianpiero Calabrese

The formulation of polyhedral boranes for the boron neutron capture therapy of cancer

The early promise of boron neutron capture therapy as a method for the treatment of cancer has been inhibited by the inherent toxicity associated with therapeutically useful doses of ¹⁰B-containing pharmacophores, the need for target-tissue specificity and the challenges imposed by biological barriers. Although developments in the synthetic chemistry of polyhedral boranes have addressed issues of toxicity to a considerable extent, the optimisation of the transport and the delivery of boronated agents to the site of action--the subject of this review--is a challenge that is addressed by the development of innovative formulation strategies.

Towards boron neutron capture therapy: The formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane

Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer.

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.

Physisorbed o-carborane onto lyso-phosphatidylcholine-functionalized, single-walled carbon nanotubes: a potential carrier system for the therapeutic delivery of boron

A combination of data from ICP-MS, Raman spectroscopy, UV-vis spectrometry, atomic force microscopy, zeta-potential measurements and gel electorphoresis studies has shown that o-carborane may be immobilized on stable aqueous dispersions of lyso-phosphatidylcholine-functionalized single-walled carbon nanotubes, which in turn indicates the potential of such structures for deployment as carrier vehicles in boron neutron capture therapy.

Labelling of electronic cigarettes: regulations and current practice

Background Over the past decade e-cigarettes have established themselves in the global market. E-cigarettes triggered much interest in relation to their content and efficacy as smoking cessation tools, but less attention has been paid to users and environmental safety warnings and guidance. Several regulations have been introduced to promote their safe handling and disposal. From May 2016, liquids and cartridges will be regulated by European Community Directives (ECDs) 2001/83/EC and 93/42/EEC, or 2014/40/EU if marketed as tobacco-related products. Currently, manufacturers and distributors must abide by the Chemical (Hazard Information and Packaging for Supply) Regulations 2009 (CHIP) or Classification, Labelling and Packaging Regulations (CLP), the latter replacing CHIP in June 2015. Objective In this work, the compliance of marketed e-liquids and e-cigarettes with current European Union and UK legislations is assessed. Results E-liquids and e-cigarettes (21 and 9 brands, respectively) were evaluated. Evidence of non-compliance was found in relation to the CHIP/CLP toxic (13%) and environmental (37%) pictograms, tactile warning (23%), nominal amount of solution (30%), supplier contact telephone number and address (40%). None of the evaluated e-cigarettes displayed information on the correct disposal/recycling of batteries in line with the ECD 2006/66/EC. Conclusions More stringent enforcement of regulations is needed to ensure not only the users safety and awareness, but also the safeguarding of the environment.

Towards carborane-functionalised structures for the treatment of brain cancer

Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with 10B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT.

Evaluation of a smart polymer nanosphere for potential use in anticancer drug delivery

Polypyrrole-chitosan (ppy-chit) hollow nanospheres have been synthesised using a simple route wherein dispersion polymerization of pyrrole was followed by treatment with aqueous ammonia, centrifugation and dialysis. Ppy-chit hollow nanospheres were characterized by techniques including transmission electron microscopy, atomic force microscopy, powder x-ray diffractometry and UV-visible spectrophotometry. The particle size and stability were assessed by using a Zetasizer. A model anticancer drug, Nile blue chloride, was loaded into the ppy-chit hollow nanospheres by adsorption, and the desorption profile showed that 88% of the dye was released at a typical physiological pH over a period of 5 hours. The combined molecular properties of chitosan and polypyrrole were beneficial to the drug delivery.

Nanotechnology in ophthalmic drug delivery

Conventional ophthalmic dosage forms are easy to prepare, administer, and their manufacture cost is relatively low. However, aqueous eye solutions suffer from very short contact time with the ocular surface and fast nasolacrimal drainage, both leading to poor bioavailability of the drug. Ointments have visibility and patient acceptably problems whereas suspensions often give rise to unpredictable and variable ocular bioavailability. To address the shortfalls of conventional ophthalmic dosage forms, nanotechnology-based systems have been investigated and some of which have been developed into marketed product. The present chapter overviews the emerging role of nanotechnology in ophthalmic drug delivery with emphasis on what has been patented over the past decade.