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Pharmaceutics
Special Issues
Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment
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Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 13106

Special Issue Editor

Dr. Sara Consalvi

E-Mail Website
Guest Editor
Department of Life Sciences, Health and Health Professions, Link Campus University, Via del Casale di San Pio V, 44, 00165 Rome, Italy
Interests: drug delivery; medicinal chemistry; drug discovery and development; antimycobacterial agents; antiviral agents; tuberculosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tuberculosis (TB) is the leading cause of death from a bacterial infection worldwide, causing an estimated 1.5 million of deaths in 2020. The spread of drug-resistant infections strongly limits treatment options and underscores the importance of finding new drugs, new bacterial targets, as well as innovative delivery systems to improve available therapeutic tools. An urgent response is then required to prevent and treat infections, limit the spread of resistance, and foster progress towards the WHO End TB strategy goal of a 90% reduction in deaths and an 80% reduction in the TB incidence rate by 2030, compared to the 2015 baseline.

This Special Issue aims to summarize recent research in the field of TB drug development, discussing state-of-the art advances and latest development in the field and covering all the aspects and stages of investigation of innovative candidates for TB treatment, including innovative delivery protocols of both existing and novel antimycobacterial agents.

Potential topics to be covered include, but are not limited to:

  • Development of novel and effective antimycobacterial agents;
  • Innovative drug delivery systems for TB treatment;
  • Innovative strategies to overcome drug resistance;
  • Emerging molecular targets for TB drug discovery;
  • Host-targeted therapies.

Dr. Sara Consalvi
Guest Editor

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

  • medicinal chemistry
  • tuberculosis
  • TB drug discovery and development
  • drug resistance
  • antimycobacterials

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Published Papers (4 papers)

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Research

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19 pages, 2540 KiB  
Article
In Vivo Toxicity, Redox-Modulating Capacity and Intestinal Permeability of Novel Aroylhydrazone Derivatives as Anti-Tuberculosis Agents
by Violeta Valcheva, Rumyana Simeonova, Milka Mileva, Stanislav Philipov, Reneta Petrova, Simeon Dimitrov, Almira Georgieva, Elina Tsvetanova, Yoana Teneva and Violina T. Angelova
Pharmaceutics 2023, 15(1), 79; https://doi.org/10.3390/pharmaceutics15010079 - 26 Dec 2022
Cited by 4 | Viewed by 2066
Abstract
The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further [...] Read more.
The emergence and spread of Mycobacterium tuberculosis strains resistant to many or all anti-tuberculosis (TB) drugs require the development of new compounds both efficient and with minimal side effects. Structure-activity-toxicity relationships of such novel, structurally diverse compounds must be thoroughly elucidated before further development. Here, we present the aroylhydrazone compounds (3a and 3b) regarding their: (i) acute and subacute toxicity in mice; (ii) redox-modulating in vivo and in vitro capacity; (iii) pathomorphology in the liver, kidney, and small intestine tissue specimens; and (iv) intestinal permeability. The acute toxicity test showed that the two investigated compounds exhibited low toxicity by oral and intraperitoneal administration. Changes in behavior, food amount, and water intake were not observed during 14 days of the oral administration at two doses of 1/10 and 1/20 of the LD50. The histological examination of the different tissue specimens did not show toxic changes. The in vitro antioxidant assays confirmed the ex vivo results. High gastrointestinal tract permeability at all tested pH values were demonstrated for both compounds. To conclude, both compounds 3a and 3b are highly permeable with low toxicity and can be considered for further evaluation and/or lead optimization. Full article
(This article belongs to the Special Issue Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment)
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21 pages, 3292 KiB  
Article
Determination of the Pharmacokinetics and Pharmacodynamics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in a Cross-Over Cynomolgus Macaque Model of Mycobacterium tuberculosis Infection
by Laura Sibley, Andrew D. White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro, Laura Alameda, Joaquin Rullas, Veronica Sousa, Marisa Martinez, Inigo Angulo-Barturen, Adolfo Garcia, Juan José Vaquero, Henry E. Pertinez, Geraint Davies, Mike Dennis, Ann Williams and Sally Sharpeadd Show full author list remove Hide full author list
Pharmaceutics 2022, 14(12), 2666; https://doi.org/10.3390/pharmaceutics14122666 - 30 Nov 2022
Viewed by 2840
Abstract
Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and [...] Read more.
Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of Mycobacterium tuberculosis (M. tb). Although the design accounted for considerable variability between animals, the three regimens evaluated could not be distinguished using any of the alternative endpoints assessed. However, the degree of pathology achieved using H37Rv in the model during this study was less than expected. Based on these findings, a second experiment using a classical AB/BA design comparing HE with HRZ was conducted using the M. tb Erdman strain. More extensive pathology was observed, and differences in computerized tomography (CT) scores and bacteriology counts in the lungs were detected, although due to the small group sizes, clearer differences were not distinguished. Type 1 T helper (Th1) cell response profiles were characterized using the IFN-γ ELISPOT assay and revealed differences between drug treatments that corresponded to decreases in disease burden. Therefore, the studies performed support the utility of the NHP model for the determination of PK/PD of TB drugs, although further work is required to optimize the use of cross-over study designs. Full article
(This article belongs to the Special Issue Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment)
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Review

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27 pages, 789 KiB  
Review
Advances of Long Non-Coding RNAs as Potential Biomarkers for Tuberculosis: New Hope for Diagnosis?
by Jiaojiao Xia, Yilin Liu, Yuhe Ma, Fen Yang, Yongdui Ruan, Jun-Fa Xu and Jiang Pi
Pharmaceutics 2023, 15(8), 2096; https://doi.org/10.3390/pharmaceutics15082096 - 7 Aug 2023
Cited by 9 | Viewed by 2237
Abstract
Tuberculosis (TB), one of the top ten causes of death globally induced by the infection of Mycobacterium tuberculosis (Mtb), remains a grave public health issue worldwide. With almost one-third of the world’s population getting infected by Mtb, between 5% and 10% of these [...] Read more.
Tuberculosis (TB), one of the top ten causes of death globally induced by the infection of Mycobacterium tuberculosis (Mtb), remains a grave public health issue worldwide. With almost one-third of the world’s population getting infected by Mtb, between 5% and 10% of these infected individuals are predicted to develop active TB disease, which would not only result in severe tissue damage and necrosis, but also pose serious threats to human life. However, the exact molecular mechanisms underlying the pathogenesis and immunology of TB remain unclear, which significantly restricts the effective control of TB epidemics. Despite significant advances in current detection technologies and treatments for TB, there are still no appropriate solutions that are suitable for simultaneous, early, rapid, and accurate screening of TB. Various cellular events can perturb the development and progression of TB, which are always associated with several specific molecular signaling events controlled by dysregulated gene expression patterns. Long non-coding RNAs (lncRNAs), a kind of non-coding RNA (ncRNA) with a transcript of more than 200 nucleotides in length in eukaryotic cells, have been found to regulate the expression of protein-coding genes that are involved in some critical signaling events, such as inflammatory, pathological, and immunological responses. Increasing evidence has claimed that lncRNAs might directly influence the susceptibility to TB, as well as the development and progression of TB. Therefore, lncRNAs have been widely expected to serve as promising molecular biomarkers and therapeutic targets for TB. In this review, we summarized the functions of lncRNAs and their regulatory roles in the development and progression of TB. More importantly, we widely discussed the potential of lncRNAs to act as TB biomarkers, which would offer new possibilities in novel diagnostic strategy exploration and benefit the control of the TB epidemic. Full article
(This article belongs to the Special Issue Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment)
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27 pages, 1394 KiB  
Review
Infant Exposure to Antituberculosis Drugs via Breast Milk and Assessment of Potential Adverse Effects in Breastfed Infants: Critical Review of Data
by Engi Abdelhady Algharably, Reinhold Kreutz and Ursula Gundert-Remy
Pharmaceutics 2023, 15(4), 1228; https://doi.org/10.3390/pharmaceutics15041228 - 13 Apr 2023
Cited by 3 | Viewed by 5130
Abstract
Infants of mothers treated for tuberculosis might be exposed to drugs via breast milk. The existing information on the exposure of breastfed infants lacks a critical review of the published data. We aimed to evaluate the quality of the existing data on antituberculosis [...] Read more.
Infants of mothers treated for tuberculosis might be exposed to drugs via breast milk. The existing information on the exposure of breastfed infants lacks a critical review of the published data. We aimed to evaluate the quality of the existing data on antituberculosis (anti-TB) drug concentrations in the plasma and milk as a methodologically sound basis for the potential risk of breastfeeding under therapy. We performed a systematic search in PubMed for bedaquiline, clofazimine, cycloserine/terizidone, levofloxacin, linezolid, pretomanid/pa824, pyrazinamide, streptomycin, ethambutol, rifampicin and isoniazid, supplemented with update references found in LactMed®. We calculated the external infant exposure (EID) for each drug and compared it with the recommended WHO dose for infants (relative external infant dose) and assessed their potential to elicit adverse effects in the breastfed infant. Breast milk concentration data were mainly not satisfactory to properly estimate the EID. Most of the studies suffer from limitations in the sample collection, quantity, timing and study design. Infant plasma concentrations are extremely scarce and very little data exist documenting the clinical outcome in exposed infants. Concerns for potential adverse effects in breastfed infants could be ruled out for bedaquiline, cycloserine/terizidone, linezolid and pyrazinamide. Adequate studies should be performed covering the scenario in treated mothers, breast milk and infants. Full article
(This article belongs to the Special Issue Drug Candidates and Drug Delivery Systems for Tuberculosis Treatment)
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