Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections

Rossi, Irene; Buttini, Francesca; Sonvico, Fabio; Affaticati, Filippo; Martinelli, F. J.; Annunziato, Giannamaria; Machado, Diana; Viveiros, Miguel; Pieroni, Marco; Bettini, Ruggero

doi:10.3390/pharmaceutics11050203

Cited by 28 publications

(11 citation statements)

References 69 publications

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“…The microparticles reduced the number of viable bacteria by more than 80% in both susceptible and drug-resistant strains of Mtb. No significant changes occurred when the same microparticles without verapamil were tested against both strains above [ 63 ]. The presence of verapamil further helped to improve the efficiency of RIF and INH in bactericidal activity.…”

Section: The Potential Of Active and Passive Targeting Approaches For Tb Treatmentmentioning

confidence: 99%

Antituberculosis Targeted Drug Delivery as a Potential Future Treatment Approach

et al. 2021

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Mycobacterium tuberculosis (Mtb) is the microorganism that causes tuberculosis. This infectious disease has been around for centuries, with the earliest record of Mtb around three million years ago. The discovery of the antituberculosis agents in the 20th century has managed to improve the recovery rate and reduce the death rate tremendously. However, the conventional antituberculosis therapy is complicated by the development of resistant strains and adverse drug reactions experienced by the patients. Research has been conducted continuously to discover new, safe, and effective antituberculosis drugs. In the last 50 years, only two molecules were approved despite laborious work and costly research. The repurposing of drugs is also being done with few drugs; antibiotics, particularly, were found to have antituberculosis activity. Besides the discovery work, enhancing the delivery of currently available antituberculosis drugs is also being researched. Targeted drug delivery may be a potentially useful approach to be developed into clinically accepted treatment modalities. Active targeting utilizes a specifically designed targeting agent to deliver a chemically conjugated drug(s) towards Mtb. Passive targeting is very widely explored, with the development of multiple types of nanoparticles from organic and inorganic materials. The nanoparticles will be engulfed by macrophages and this will eliminate the Mtb that is present in the macrophages, or the encapsulated drug may be released at the sites of infections that may be in the form of intra- and extrapulmonary tuberculosis. This article provided an overview on the history of tuberculosis and the currently available treatment options, followed by discussions on the discovery of new antituberculosis drugs and active and passive targeting approaches against Mycobacterium tuberculosis.

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Section: The Potential Of Active and Passive Targeting Approaches For Tb Treatmentmentioning

confidence: 99%

Antituberculosis Targeted Drug Delivery as a Potential Future Treatment Approach

et al. 2021

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“…The highly respirable microparticles showed successful intracellular anti‐TB activity on both susceptible and resistant Mtb strain‐infected macrophages. [ 148 ]…”

Section: Nanotechnology‐based Drug Delivery Systemsmentioning

confidence: 99%

“…The highly respirable microparticles showed successful intracellular anti-TB activity on both susceptible and resistant Mtb strain-infected macrophages. [148] Silva et al encapsulated the LLKKK18 antimicrobial peptide (AMP) into self-assembling HA nanogels. With this formulation, the cytotoxicity of LLKKK18 was outstandingly reduced in vitro on murine-bone-marrow-derived macrophages as compared to the free AMP.…”

Section: Hyaluronic Acid Receptor Targetingmentioning

confidence: 99%

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Baranyai

Soria‐Carrera

Alleva

et al. 2020

Advanced Therapeutics

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The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial‐loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment.

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“…Moreover, both of the formulations (with or without VPM) showed antimycobacterial activity with a combined MIC 99 of 0.25 µg/mL and a combined MIC of 32 µg/mL for the susceptible strain H37Rv and two-drugs resistant strains, respectively. In an ex vivo study, both formulations were able to reduce bacterial viability to less than 20% irrespective of the drug resistance profile at day 3 post-infection [ 149 ]. This formulation thus showed strong scientific evidence of suitability in enhancing the macrophage elimination of mycobacteria, irrespective of the drug-resistance profile.…”

Section: Novel Approaches For Dry Powder Inhalable Lung Drug Delivmentioning

confidence: 99%

Novel Approaches for the Treatment of Pulmonary Tuberculosis

et al. 2020

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Tuberculosis (TB) is a contagious airborne disease caused by Mycobacterium tuberculosis, which primarily affects human lungs. The progression of drug-susceptible TB to drug-resistant strains, MDR-TB and XDR-TB, has become worldwide challenge in eliminating TB. The limitations of conventional TB treatment including frequent dosing and prolonged treatment, which results in patient’s noncompliance to the treatment because of treatment-related adverse effects. The non-invasive pulmonary drug administration provides the advantages of targeted-site delivery and avoids first-pass metabolism, which reduced the dose requirement and systemic adverse effects of the therapeutics. With the modification of the drugs with advanced carriers, the formulations may possess sustained released property, which helps in reducing the dosing frequency and enhanced patients’ compliances. The dry powder inhaler formulation is easy to handle and storage as it is relatively stable compared to liquids and suspension. This review mainly highlights the aerosolization properties of dry powder inhalable formulations with different anti-TB agents to understand and estimate the deposition manner of the drug in the lungs. Moreover, the safety profile of the novel dry powder inhaler formulations has been discussed. The results of the studies demonstrated that dry powder inhaler formulation has the potential in enhancing treatment efficacy.

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Sodium Hyaluronate Nanocomposite Respirable Microparticles to Tackle Antibiotic Resistance with Potential Application in Treatment of Mycobacterial Pulmonary Infections

Cited by 28 publications

References 69 publications

Antituberculosis Targeted Drug Delivery as a Potential Future Treatment Approach

Antituberculosis Targeted Drug Delivery as a Potential Future Treatment Approach

Nanotechnology‐Based Targeted Drug Delivery: An Emerging Tool to Overcome Tuberculosis

Novel Approaches for the Treatment of Pulmonary Tuberculosis

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