Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates’ therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers.
Headache disorders are considered the second leading cause of years lived with disability worldwide, and 90% of people have a headache episode at least once a year, thus representing a relevant public health priority. As the pharmacist is often the first and only point of reference for people complaining of headache, we carried out a survey in a nationwide sample of Italian pharmacies, in order to describe the distribution of migraine or non-migraine type headaches and medicines overuse among people entering pharmacies seeking for self-medication; and to evaluate the association, in particular of migraine, with socio-demographic and clinical characteristics, and with the pathway of care followed by the patients. A 14-item questionnaire, including socio-demographic and clinical factors, was administered by trained pharmacists to subjects who entered a pharmacy requesting self-medication for a headache attack. The ID Migraine™ Screener was used to classify headache sufferers in four classes. From June 2016 to January 2017, 4424 people have been interviewed. The prevalence of definite migraines was 40%, significantly higher among women and less educated people. About half of all headache sufferers and a third of migraineurs do not consider their condition as a disease and are not cared by any doctor. Among people seeking self-medication in pharmacies for acute headache attacks, the rate of definite or probable migraine is high, and a large percentage of them is not correctly diagnosed and treated. The pharmacy can be a valuable observatory for the study of headaches, and the first important step to improve the quality of care delivered to these patients.
Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation.
Current legislation in Italy provides that medical Cannabis may be administered orally or by inhalation. One of the fundamental criteria for the administration of oral formulations is that they deliver a known consistent quantity of the active ingredients to ensure uniform therapies leading to the optimisation of the risks/benefits. In 2018, our group developed an improved Cannabis oil extraction technique. The objective of the present work was to carry out a stability study for the oil extracts obtained by this method. Furthermore, in order to facilitate the consumption of the prescribed medical Cannabis therapy by patients, a standard procedure was defined for the preparation of a single-dose preparation for oral use (hard capsules) containing the oil extract; thereafter, the quality and stability were evaluated. The hard capsules loaded with the oil extract were analysed and found to be uniform in content. The encapsulation process did not alter the quantity of the active molecule present in the oil. The stability tests yielded excellent results. Since the capsule dosage form is easily transported and administered, has pleasant organoleptic properties and is stable at room temperature for extended periods of time, this would facilitate the adherence to therapy by patients in treatment.