Paediatric formulation: Design and development

The development of medicines designed for children can be challenging since this distinct patient population requires specific needs. A formulation designed for paediatric patients must consider the following aspects: patient population variability; dose flexibility; route of administration; patient compliance; drug and excipient tolerability. The purpose of this Special Issue entitled “Paediatric Formulation: Design and Development” is to provide an update on both state-of-the-art methodology and operational challenges in the design and development of paediatric formulations. It aims at re-evaluating what is needed for more progress in the design and development of age-appropriate treatments for paediatric diseases, focusing on: formulation development; drug delivery design; efficacy, safety, and tolerability of drugs and excipients. This editorial, briefly, summarizes the objects of nine original research and review papers published in this Special Issue

In vivo synthesis of monolysocardiolipin and cardiolipin by Acinetobacter baumannii phospholipase D and effect on cationic antimicrobial peptide resistance

Acinetobacter baumannii is an opportunistic pathogen, which has become a rising threat in healthcare facilities worldwide due to increasing antibiotic resistances and optimal adaptation to clinical environments and the human host. We reported in a former publication on the identification of three phopholipases of the phospholipase D (PLD) superfamily in A. baumannii ATCC 19606T acting in concerted manner as virulence factors in Galleria mellonella infection and lung epithelial cell invasion. This study focussed on the function of the three PLDs. A Δpld1-3 mutant was defect in biosynthesis of the phospholipids cardiolipin (CL) and monolysocardiolipin (MLCL), whereas the deletion of pld2 and pld3 abolished the production of MLCL. Complementation of the Δpld1-3 mutant with pld1 restored CL biosynthesis demonstrating that the PLD1 is implicated in CL biosynthesis. Complementation of the Δpld1-3 mutant with either pld2 or pld3 restored MLCL and CL production leading to the conclusion that PLD2 and PLD3 are implicated in CL and MLCL production. Mutant studies revealed that two catalytic motifs are essential for the PLD3-mediated biosynthesis of CL and MLCL. The Δpld1-3 mutant exhibited a decreased colistin and polymyxin B resistance indicating a role of CL in cationic antimicrobial peptides (CAMPs) resistance

Bridging Pharmaceutical Chemistry with Drug and Nanoparticle Targeting to Investigate the Role of the 18-kDa Translocator Protein TSPO.

An interesting mitochondrial biomarker is the 18‐kDa mitochondrial translocator protein (TSPO). Decades of study have shown that this protein plays an important role in a wide range of cellular functions, including opening of the mitochondrial permeability transition pore as well as programmed cell death and proliferation. Variations in TSPO expression have been correlated to different diseases, from tumors to endocrine and neurological disorders. TSPO has therefore become an appealing target for both early diagnosis and selective mitochondrial drug delivery. The number of structurally different TSPO ligands examined has increased over time, highlighting the scientific community′s growing understanding of the roles of TSPO in normal and pathological conditions. However, only few TSPO ligands are characterized by the presence of groups that are potentially derivatizable; therefore only few such ligands are well suited for the preparation of targeted prodrugs or nanocarriers able to deliver therapeutics and/or diagnostic agents to mitochondria. This review provides an overview of the very few examples of drug delivery systems characterized by moieties that target TSPO

Bcr-abl tyrosine kinase inhibitors in the treatment of pediatric cml

The therapeutic approach to Chronic Myeloid Leukemia (CML) has changed since the advent of the tyrosine kinase inhibitor (TKI) imatinib, which was then followed by the second generation TKIs dasatinib, nilotinib, and, finally, by ponatinib, a third-generation drug. At present, these therapeutic options represent the first-line treatment for adults. Based on clinical experience, imatinb, dasatinib, and nilotinib have been approved for children even though the studies that were concerned with efficacy and safety toward pediatric patients are still awaiting more specific and high-quality data. In this scenario, it is of utmost importance to prospectively validate data extrapolated from adult studies to set a standard therapeutic management for pediatric CML by employing appropriate formulations on the basis of pediatric clinical trials, which allow a careful monitoring of TKI-induced adverse effects especially in growing children exposed to long-term therapy

Can Digital Tools Be Used for Improving Immunization Programs?

In order to successfully control and eliminate vaccine-preventable infectious diseases, an appropriate vaccine coverage has to be achieved and maintained. This task requires a high level of effort as it may be compromised by a number of barriers. Public health agencies have issued specific recommendations to address these barriers and therefore improve immunization programs. In the present review, we characterize issues and challenges of immunization programs for which digital tools are a potential solution. In particular, we explore previously published research on the use of digital tools in the following vaccine-related areas: immunization registries, dose tracking, and decision support systems; vaccine-preventable diseases surveillance; surveillance of adverse events following immunizations; vaccine confidence monitoring; and delivery of information on vaccines to the public. Subsequently, we analyze the limits of the use of digital tools in such contexts and envision future possibilities and challenges

Stability data of extemporaneous suspensions of hydroxychloroquine sulphate in oral liquid bases after tablet manipulation

Hydroxychloroquine is a well-known anti-malarial and anti-rheumatic drug that has garnered recently unprecedented attention as potential therapeutic agent against virus infections. Hydroxychloroquine sulphate is authorized in the EU as film-coated tablets (i.e. Plaquenil®), which cannot be administered to non-cooperative patients, such as those in intensive care units or, more in general, unable to swallow solid dosage forms. Therefore, the hospital pharmacist must manipulate the solid dosage form for the preparation of suspension, even if it can strongly affect the product quality. In this scenario, it is crucial to offer useful information and advice to assist hospital pharmacists in their activity. The data presented in this article suggest that extemporaneous suspensions of hydroxychloroquine sulphate in oral liquid bases after tablet manipulation are stable for at least 30 days

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates

Covid-19 vaccination programme effectiveness against SARS-CoV-2 related infections, hospital admissions and deaths in the Apulia region of Italy: a one-year retrospective cohort study

: Studies reporting vaccine effectiveness against COVID-19 outcomes concentrate mainly on estimates of one single type of vaccine and variant, seldom considering waning effects. We aimed to estimate the effectiveness of the overall COVID-19 vaccination programme implemented in the Apulia region of Italy at preventing SARS-CoV-2 infections, COVID-19-related hospital admissions and deaths during alpha and delta variant dominant periods. We conducted a retrospective cohort study using electronic health records of persons 16 years and older resident in the Apulia region, assessing the effectiveness of the combined use of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines against confirmed COVID-19 infections, hospitalisations and deaths, for fully and partially vaccinated persons as well as by time since vaccination and variants. Cox regression models yielding hazard ratios were used to calculate the overall vaccination programme effectiveness. From 1 January to 1 December 2021, we included 3,530,967 eligible persons in the cohort, of whom 2,770,299 were fully vaccinated and 158,313 were COVID-19 positive at the end of the study period. The effectiveness of the programme over the entire study period for fully vaccinated persons against COVID-19 infection, hospitalisation and death were 87.69% (CI95% 87.73-88.18), 94.08% (93.58-94.54) and 95.95% (CI95% 95.26-96.54), respectively. The effectiveness against COVID-19 infection of fully vaccinated subjects during the alpha and delta period was respectively 88.20% (CI95% 87.60-99.78) and 59.31% (CI95% 57.91-60.67), against hospitalisation 93.89% (CI95% 92.67-94.90) and 88.32% (CI95% 86.50-89.90) and against death 93.83% (CI95% 91.65-95.45) and 85.91 (CI95% 79.98-90.09). The waning effects of the programme regarding COVID-19 infection during the delta period were stronger than for alpha, with 75.85% (CI95% 74.38-77.24) effectiveness after 1-2 months and 8.35% (CI95% 3.45-13.01) after 5-6 months after full vaccination. The effectiveness against hospitalisation and death during the delta period waned rapidly and at 7-8-months after the full vaccination respectively decreased to 27.67% (CI95% 7.48-43.45) and 48.47 (CI95% 53.97-34.82). Our study suggests that the COVID-19 vaccination program in Apulia was strongly protective against COVID-19 infection, hospitalisation, and death due to alpha as well as delta variants, although its effectiveness is reduced over time