Recent Advances in Therapeutic Strategies for the Treatment of Pediatric Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 24 September 2024 | Viewed by 12843

Special Issue Editors


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Guest Editor
Clinical Pathology, Pausilipon Hospital, A.O.R.N Santobono-Pausilipon, 80123 Naples, Italy
Interests: non coding RNA in cancer development; post-transcriptional regulation; effects of plant nanovesicles on cancer in vitro models; study of new therapeutic strategies for pediatric cancer diseases

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Guest Editor
Clinical and Translational Research Unit, Santobono-Pausilipon Children’s Hospital, 80129 Naples, Italy
Interests: cancer; leukemia; flow cytometry; microRNA; lncRNA; Alzheimer’s disease
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Special Issue Information

Dear Colleagues,

we are pleased to invite you to contribute to the Special Issue entitled “Recent Advances in Therapeutic Strategies for the Treatment of Pediatric Diseases”.

Gene therapy, biological drugs and innovative treatments are opening up new opportunities for diagnosis and treatment of children affected by different diseases such as immunodeficiencies, tumors, hematological disorders, genetic diseases and so on. Although to date a number of pediatric diseases are efficiently treated, any efforts in the development of new therapeutical strategies is appreciated in order to reduce side effects and ameliorate the life style of affected children.

This Special Issue aims to publish contributions on the different aspects related to the treatment of pediatric diseases. All types of articles are welcome, we encourage the submission of original research reports, reviews, minireviews, and perspectives focusing on the following specific topics regarding the treatment of pediatric diseases:

  • Effects of new drugs/compounds on in vitro and in vivo systems.
  • Identification of causative mutations and elucidation of molecular basis in pediatric diseases in order to design specific/personalized drugs.
  • Identification of biomarkers to follow up novel therapies.
  • Physiological and biochemical effects of drugs on the body.
  • Gene therapy.
  • Delivery systems for drugs, vaccines and biopharmaceuticals.

We look forward to receiving your contributions.

Dr. Mariaevelina Alfieri
Dr. Peppino Mirabelli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pediatric diseases 
  • drug discovery 
  • gene therapy 
  • drug delivery 
  • novel therapies 
  • new biomarkers 
  • molecular basis 
  • gene mutations 
  • therapeutic targets

Published Papers (6 papers)

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Research

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18 pages, 3281 KiB  
Article
AmBisome® Formulations for Pediatrics: Stability, Cytotoxicity, and Cost-Effectiveness Studies
by Guendalina Zuccari, Carla Villa, Valentina Iurilli, Paola Barabino, Alessia Zorzoli, Danilo Marimpietri, Debora Caviglia and Eleonora Russo
Pharmaceutics 2024, 16(4), 466; https://doi.org/10.3390/pharmaceutics16040466 - 27 Mar 2024
Viewed by 1355
Abstract
Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be [...] Read more.
Liposomal amphotericin B (Ambisome®) is the gold standard for the treatment and prevention of fungal infections both in the adult and pediatric populations. The lyophilized dosage form has to be reconstituted and diluted by hospital staff, but its management can be challenging due to the spontaneous tendency of amphotericin B to form aggregates with different biological activity. In this study, the colloidal stability of the liposomes and the chemical stability of amphotericin B were investigated over time at storage conditions. Three liposomal formulations of amphotericin B at 4.0 mg/mL, 2.0 mg/mL, and 0.2 mg/mL were prepared and assayed for changes regarding the dimensional distribution, zeta potential, drug aggregation state, and onset of by-products. Our analyses highlighted that the most diluted formulation, kept at room temperature, showed the greatest changes in the aggregation state of the drug and accordingly the highest cytotoxicity. These findings are clinically relevant since the lower dosages are addressed to the more vulnerable patients. Therefore, the centralization of the dilution of AmBisome® at the pharmacy is of fundamental importance for assuring patient safety, and at the same time for reducing medication waste, as we demonstrated using the cost-saving analysis of drug expense per therapy carried out at the G. Gaslini children hospital. Full article
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14 pages, 2390 KiB  
Article
Dispensing Oral Temozolomide in Children: Precision and Stability of a Novel and Ready to Use Liquid Formulation in Comparison with Capsule Derived Mixtures
by Caroline Lemarchand, Hugues Bienaymé, André Rieutord, Samuel Abbou, Maxime Annereau and Jeremy Bastid
Pharmaceutics 2023, 15(12), 2711; https://doi.org/10.3390/pharmaceutics15122711 - 30 Nov 2023
Viewed by 1563
Abstract
Temozolomide (TMZ) is part of the therapeutic armamentarium used in managing pediatric cancers; however, available oral forms (capsules) are not adapted for use in children. Our aim was to assess the dose accuracy and stability of TMZ using capsule contents mixed with food [...] Read more.
Temozolomide (TMZ) is part of the therapeutic armamentarium used in managing pediatric cancers; however, available oral forms (capsules) are not adapted for use in children. Our aim was to assess the dose accuracy and stability of TMZ using capsule contents mixed with food compared with a novel, ready-to-use liquid formulation specifically developed for children (Ped-TMZ, brand name KIZFIZO). Dose accuracy and TMZ stability testing were performed with TMZ capsule contents (90 mg) mixed with food vehicles (apple juice, apple sauce, cream, milk, and mashed potatoes) and compared to an equivalent dose of Ped-TMZ. Acceptance criteria were predefined for TMZ (95.0–105.0%) and its degradation product amino-imidazole-carboxamide (AIC; <1%) content. The delivered dose was significantly higher using Ped-TMZ (96.6 ± 1.2%) and within the predefined criteria for TMZ content, whereas it was systematically under the lower specifications of 95% using capsule-derived preparations with apple juice (91.0 ± 1.5%) and apple sauce (91.6 ± 1.4%), respectively (p < 0.0001). In chemical stability tests, the four food vehicles (apple sauce, cream, milk, mashed potatoes) had a significant effect on TMZ stability (p = 0.0042), and the AIC significantly increased with time in three of the four vehicles (p < 0.0001). Only 1/72 of preparations from capsules met the predefined acceptance criteria, whereas Ped-TMZ showed no TMZ loss, and the AIC remained within specifications. In conclusion, mixing TMZ capsule content with food may result in significant underexposure, possibly even greater in routine practice, as complete food intake by the child is unlikely. Full article
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20 pages, 2027 KiB  
Article
A Multicenter Randomized Bioequivalence Study of a Novel Ready-to-Use Temozolomide Oral Suspension vs. Temozolomide Capsules
by François Ducray, Carole Ramirez, Marie Robert, Maxime Fontanilles, Charlotte Bronnimann, Olivier Chinot, Florian Estrade, Xavier Durando, Stéphanie Cartalat, Jeremy Bastid, Hugues Bienayme and Caroline Lemarchand
Pharmaceutics 2023, 15(12), 2664; https://doi.org/10.3390/pharmaceutics15122664 - 24 Nov 2023
Viewed by 1623
Abstract
Background: Temozolomide (TMZ) oral suspension (Ped-TMZ, KIZFIZO®) is being developed for the treatment of relapsed or refractory neuroblastoma, a rare cancer affecting infants and young children. The study assessed the safety and the bioequivalence of this novel pediatric formulation with existing [...] Read more.
Background: Temozolomide (TMZ) oral suspension (Ped-TMZ, KIZFIZO®) is being developed for the treatment of relapsed or refractory neuroblastoma, a rare cancer affecting infants and young children. The study assessed the safety and the bioequivalence of this novel pediatric formulation with existing TMZ oral capsules. Methods: In vitro dissolution profiles and the bioequivalence were evaluated following the European Medicines Agency “Guidelines on the investigation of Bioequivalence”. The phase I, multicenter, randomized, open-label, crossover, single-dose bioequivalence study enrolled 36 adult patients with glioblastoma multiforme or lower-grade glioma. Each patient received 200 mg/m2 Ped-TMZ suspension and TMZ capsules (Temodal®) on 2 consecutive days, with the order being randomly assigned. Fourteen blood samples were collected up to 10 h post-dosing. Bioequivalence was assessed by comparing the 90% confidence interval for the ratio of the geometric means of maximum TMZ plasma concentration (Cmax) and the area under the curve (AUCt). Other endpoints included further pharmacokinetic parameters and safety. Results: Both formulations exhibited a fast in vitro dissolution profile with more than 85% of TMZ dissolved within 15 min. For the bioequivalence study, thirty patients completed the trial as per the protocol. The ratio of Ped-TMZ/TMZ capsule geometric means (90% CI) for AUCt and Cmax were 97.18% (95.05–99.35%) and 107.62% (98.07–118.09%), respectively, i.e., within the 80–125% bioequivalence limits. No buccal toxicity was associated with Ped-TMZ liquid formulation. Conclusions: This study showed that Ped-TMZ oral suspension and TMZ oral capsule treatment are immediate release and bioequivalent medicines. There were also no unexpected safety signals or local toxicity (funded by ORPHELIA Pharma; ClinicalTrials.gov number, NCT04467346). Full article
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Review

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19 pages, 856 KiB  
Review
Circulating Biomarkers for Monitoring Chemotherapy-Induced Cardiotoxicity in Children
by Luigia Meo, Maria Savarese, Carmen Munno, Peppino Mirabelli, Pia Ragno, Ornella Leone and Mariaevelina Alfieri
Pharmaceutics 2023, 15(12), 2712; https://doi.org/10.3390/pharmaceutics15122712 - 30 Nov 2023
Viewed by 1455
Abstract
Most commonly diagnosed cancer pathologies in the pediatric population comprise leukemias and cancers of the nervous system. The percentage of cancer survivors increased from approximatively 50% to 80% thanks to improvements in medical treatments and the introduction of new chemotherapies. However, as a [...] Read more.
Most commonly diagnosed cancer pathologies in the pediatric population comprise leukemias and cancers of the nervous system. The percentage of cancer survivors increased from approximatively 50% to 80% thanks to improvements in medical treatments and the introduction of new chemotherapies. However, as a consequence, heart disease has become the main cause of death in the children due to the cardiotoxicity induced by chemotherapy treatments. The use of different cardiovascular biomarkers, complementing data obtained from electrocardiogram, echocardiography cardiac imaging, and evaluation of clinical symptoms, is considered a routine in clinical diagnosis, prognosis, risk stratification, and differential diagnosis. Cardiac troponin and natriuretic peptides are the best-validated biomarkers broadly accepted in clinical practice for the diagnosis of acute coronary syndrome and heart failure, although many other biomarkers are used and several potential markers are currently under study and possibly will play a more prominent role in the future. Several studies have shown how the measurement of cardiac troponin (cTn) can be used for the early detection of heart damage in oncological patients treated with potentially cardiotoxic chemotherapeutic drugs. The advent of high sensitive methods (hs-cTnI or hs-cTnT) further improved the effectiveness of risk stratification and monitoring during treatment cycles. Full article
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20 pages, 920 KiB  
Review
Off-Label Prescribing in Pediatric Population—Literature Review for 2012–2022
by Valentina Petkova, Dilyana Georgieva, Milen Dimitrov and Irina Nikolova
Pharmaceutics 2023, 15(12), 2652; https://doi.org/10.3390/pharmaceutics15122652 - 21 Nov 2023
Cited by 4 | Viewed by 3399
Abstract
Off-label prescribing is widespread among pediatricians, and it is unlikely that this trend will soon be bound by a uniform legal framework. This is necessitated by the fact that there are four variables: the patient’s health condition, the physician’s experience and knowledge, the [...] Read more.
Off-label prescribing is widespread among pediatricians, and it is unlikely that this trend will soon be bound by a uniform legal framework. This is necessitated by the fact that there are four variables: the patient’s health condition, the physician’s experience and knowledge, the legislative measures (laws, directives, guidelines, and recommendations), and finally, the pharmaceutical industry. There is considerable concern worldwide about the use of off-label medicines in children. We may call it an enormous global problem that is much talked about and written about; however, we should not forget that the goal around which everyone should unite is the patient’s life. For healthcare providers, the most important thing will always be the health and preservation of the patient’s life, particularly when it comes to children with life-threatening conditions in neonatal and pediatric intensive care units (NICU and PICU). The study aimed to examine the prevalence of off-label drug use in pediatrics. Literature research was conducted, and we included studies from 2012 to 2022 that evaluated off-label drug prevalence in various pediatric patient populations. Full article
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12 pages, 313 KiB  
Review
Expanding the Availability of Onasemnogene Abeparvovec to Older Patients: The Evolving Treatment Landscape for Spinal Muscular Atrophy
by Charlotte A. René and Robin J. Parks
Pharmaceutics 2023, 15(6), 1764; https://doi.org/10.3390/pharmaceutics15061764 - 19 Jun 2023
Cited by 1 | Viewed by 2527
Abstract
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival of motor neuron 1 (SMN1) gene, which leads to a reduced level in the SMN protein within cells. Patients with SMA suffer from a loss of [...] Read more.
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the survival of motor neuron 1 (SMN1) gene, which leads to a reduced level in the SMN protein within cells. Patients with SMA suffer from a loss of alpha motor neurons in the spinal cord leading to skeletal muscle atrophy in addition to deficits in other tissues and organs. Patients with severe forms of the disease require ventilator assistance and typically succumb to the disease due to respiratory failure. Onasemnogene abeparvovec is an adeno-associated virus (AAV)-based gene therapeutic that has been approved for infants and young children with SMA, and it is delivered through intravenous administration using a dose based on the weight of the patient. While excellent outcomes have been observed in treated patients, the greater viral dose necessary to treat older children and adults raises legitimate safety concerns. Recently, onasemnogene abeparvovec use was investigated in older children through a fixed dose and intrathecal administration, a route that provides a more direct delivery to affected cells in the spinal cord and central nervous system. The promising results observed in the STRONG trial may support approval of onasemnogene abeparvovec for a greater proportion of patients with SMA. Full article
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