ArticlePharmaceutical research2016
Preparation and Preclinical Evaluation of Inhalable Particles Containing Rapamycin and Anti-Tuberculosis Agents for Induction of Autophagy.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Antimicrobial peptides for tuberculosis in a post-antibiotic era: from in vitro promise to therapeutic potential.npj antimicrobials and resistance · 2026Review
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.Infection and immunity · 2025Review
- Tristetraprolin mediates immune evasion of mycobacterial infection in macrophages.FASEB bioAdvances · 2024Article
- Review
- Exploring and exploiting the host cell autophagy during Mycobacterium tuberculosis infection.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2023Review
- Review
- Inhaled Adjunct Therapy with Second-Line Drug Candidates for Dose Reduction in Chemotherapeutic Regimens for Multi-drug-Resistant Tuberculosis.AAPS PharmSciTech · 2023Article
- A review of formulations and preclinical studies of inhaled rifampicin for its clinical translation.Drug delivery and translational research · 2023Review
- Article
- Recent advances in PLGA micro/nanoparticle delivery systems as novel therapeutic approach for drug-resistantFrontiers in bioengineering and biotechnology · 2022Review
- Repurposing diphenylbutylpiperidine-class antipsychotic drugs for host-directed therapy of Mycobacterium tuberculosis and Salmonella enterica infections.Scientific reports · 2021Article
- Understanding the Reciprocal Interplay Between Antibiotics and Host Immune System: How Can We Improve the Anti-Mycobacterial Activity of Current Drugs to Better Control Tuberculosis?Frontiers in immunology · 2021Review
- Genome-Wide Gene Expression Analysis of Mtb-Infected DC Highlights the Rapamycin-Driven Modulation of Regulatory CytokinesFrontiers in immunology · 2021Article
- Transient Transfection of the Respiratory Epithelium with Gamma Interferon for Host-Directed Therapy in Pulmonary Tuberculosis.Molecular therapy. Nucleic acids · 2020Article
- Feasibility of Aerosolized Alpha-1 Antitrypsin as a Therapeutic Option.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Targeting Autophagy as a Strategy for Developing New Vaccines and Host-Directed Therapeutics Against Mycobacteria.Frontiers in microbiology · 2020Review
- Autophagy Modulators: Mechanistic Aspects and Drug Delivery Systems.Biomolecules · 2019Review
- Animal models of tuberculosis: Lesson learnt.The Indian journal of medical research · 2018Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMycobacterium tuberculosis (Mtb) inhibits host defense mechanisms, including autophagy. We investigated particles containing rapamycin (RAP) alone or in combination with isoniazid (INH) and rifabutin (RFB) for: targeting lung macrophages on inhalation; inducing autophagy; and killing macrophage-resident Mtb and/or augmenting anti-tuberculosis (TB) drugs.
methodsPLGA and drugs were spray-dried. Pharmacokinetics, partial biodistribution (LC-MS/MS) and efficacy (colony forming units, qPCR, acid fast staining, histopathology) in mice following dry powder inhalation were evaluated.
resultsAerodynamic diameters of formulations were 0.7-4.7 μm. Inhaled particles reached deep lungs and were phagocytosed by alveolar macrophages, yielding AUC0-48 of 102 compared to 0.1 μg/ml × h obtained with equivalent intravenous dose. RAP particles induced more autophagy in Mtb-infected macrophages than solutions. Inhaled particles containing RAP alone in daily, alternate-day and weekly dosing regimens reduced bacterial burden in lungs and spleens, inducing autophagy and phagosome-lysosome fusion. Inhalation of particles containing RAP with INH and RFB cleared the lungs and spleens of culturable bacteria.
conclusionsTargeting a potent autophagy-inducing agent to airway and lung macrophages alone is feasible, but not sufficient to eliminate Mtb. Combination of macrophage-targeted inhaled RAP with classical anti-TB drugs contributes to restoring tissue architecture and killing Mtb.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.