100 Years of Drug Delivery to the Lungs

Lavorini, Federico; Buttini, Francesca; Usmani, Omar

doi:10.1007/164_2019_335

Cited by 39 publications

(50 citation statements)

References 41 publications

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“…Nebulizers (including jet, ultrasonic wave, and vibrating mesh nebulizers) are the only inhalation device systems that have been used in pilot studies and clinical trials (Table 1). This inhalation device is able to aerosolize an aqueous liquid formulation into droplets of below 5 µm that are able to be driven into and deposited in the lungs with the patient's inspiration [13]. However, during the aerosolization process, a large part of the aerosol is lost in the device and in the air [13], which is a serious concern for cytotoxic chemotherapy [15,41].…”

Section: Article Highlightsmentioning

confidence: 99%

“…Inhalation, or pulmonary drug delivery, is an advantageous route of administration to treat pulmonary disorders. It has become the main route of administration of treatment against asthma or chronic obstructive pulmonary disease (COPD) and is used also to treat some pulmonary infections often encountered in cystic fibrosis or to treat pulmonary hypertension [13,14]. This noninvasive route of administration presents many advantages over systemic deliveries such as the oral or intravenous (iv) routes.…”

Section: Introductionmentioning

confidence: 99%

“…These have a favorable pharmacokinetic profile because they limit systemic adverse effects and the first-pass metabolism by concentrating the drug into the site of action. This route of administration allows a lower dose to have a rapid onset and to have the same effect as a higher dose delivered by systemic routes [13,14]. These numerous advantages have led to this route of administration being evaluated for lung cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

Wauthoz

Rosière

Amighi

2020

Expert Opinion on Drug Delivery

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Introduction: Since 1968, inhaled chemotherapy has been evaluated and has shown promising results up to phase II but has not yet reached the market. This is due to technological and clinical challenges that require to be overcome with the aim of optimizing the efficacy and the tolerance of drug to reopen new developments in this field. Moreover, recent changes in the therapeutic standard of care for treating the patient with lung cancer also open new opportunities to combine inhaled chemotherapy with standard treatments. Areas covered: Clinical and technological concerns are highlighted from the reported clinical trials made with inhaled cytotoxic chemotherapies. This work then focuses on new pharmaceutical developments using dry powder inhalers as inhalation devices and on formulation strategies based on controlled drug release and with sustained lung retention or based on nanomedicine. Finally, new clinical strategies are described in regard to the impact of the immunotherapy on the patient's standard of care. Expert opinion: The choice of the drug, inhalation device, and formulation strategy as well as the position of inhaled chemotherapy in the patient's clinical care are crucial factors in optimizing local tolerance and efficacy as well as in its scalability and applicability in clinical practice.

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Section: Article Highlightsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

Wauthoz

Rosière

Amighi

2020

Expert Opinion on Drug Delivery

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“…The SMI was placed at the medication inlet port, which was designed in an oval shape to fit the SMI, and then parallel to the Y-piece inspiratory limb [8]. (2). A T-adapter commonly used for a jet nebulizer was placed between the Y-piece of the ventilator circuit and the inspiratory limb ( Figure 1B).…”

Section: Smi Delivery In the Ventilator Systemmentioning

confidence: 99%

“…Aerosol therapy plays a critical role in treating pulmonary and non-pulmonary diseases. Currently, more than 250 inhalers are available for delivering drugs as a component of treatment [1,2]. The soft mist inhaler (SMI) is a propellant-free, mechanically operated, multiple-dose device, which nebulizes a liquid drug solution through a uniblock, which allows the drug solution to produce aerosol in a slow-moving cloud with a spray time of 1.0-1.5 s [3].…”

Section: Introductionmentioning

confidence: 99%

Optimal Connection for Tiotropium SMI Delivery through Mechanical Ventilation: An In Vitro Study

et al. 2020

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We aimed to quantify Soft Mist Inhalers (SMI) delivery to spontaneous breathing model and compare with different adapters via endotracheal tube during mechanical ventilation or by manual resuscitation. A tiotropium SMI was used with a commercial in-line adapter and a T-adapter placed between the Y-adapter and the inspiratory limb of the ventilator circuit during mechanical ventilation. The SMI was actuated at the beginning of inspiration and expiration. In separate experiments, a manual resuscitator with T-adapter was attached to endotracheal tube, collecting filter, and a passive test lung. Drug was eluted from collecting filters with salt-based solvent and analyzed using high-performance liquid chromatography. Results showed the percent of SMI label dose inhaled was 3-fold higher with the commercial in-line adapter with actuation during expiration than when synchronized with inspiration. SMI with T-adapter delivery via ventilator was similar to inhalation (1.20%) or exhalation (1.02%), and both had lower delivery dose than with manual resuscitator (2.80%; p = 0.01). The inhaled dose via endotracheal tube was much lower than inhaled dose with spontaneous breathing (22.08%). In conclusion, the inhaled dose with the commercial adapter was higher with SMI actuated during expiration, but still far less than reported spontaneous inhaled dose.

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Polyester nanoparticles delivering chemotherapeutics: Learning from the past and looking to the future to enhance their clinical impact in tumor therapy

Longobardi,

Moore,

Conte

et al. 2024

WIREs Nanomed Nanobiotechnol

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Polymeric nanoparticles (NPs), specifically those comprised of biodegradable and biocompatible polyesters, have been heralded as a game‐changing drug delivery platform. In fact, poly(α‐hydroxy acids) such as polylactide (PLA), poly(lactide‐co‐glycolide) (PLGA), and poly(ε‐caprolactone) (PCL) have been heavily researched in the past three decades as the material basis of polymeric NPs for drug delivery applications. As materials, these polymers have found success in resorbable sutures, biodegradable implants, and even monolithic, biodegradable platforms for sustained release of therapeutics (e.g., proteins and small molecules) and diagnostics. Few fields have gained more attention in drug delivery through polymeric NPs than cancer therapy. However, the clinical translational of polymeric nanomedicines for treating solid tumors has not been congruent with the fervor or funding in this particular field of research. Here, we attempt to provide a comprehensive snapshot of polyester NPs in the context of chemotherapeutic delivery. This includes a preliminary exploration of the polymeric nanomedicine in the cancer research space. We examine the various processes for producing polyester NPs, including methods for surface‐functionalization, and related challenges. After a detailed overview of the multiple factors involved with the delivery of NPs to solid tumors, the crosstalk between particle design and interactions with biological systems is discussed. Finally, we report state‐of‐the‐art approaches toward effective delivery of NPs to tumors, aiming at identifying new research areas and re‐evaluating the reasons why some research avenues have underdelivered. We hope our effort will contribute to a better understanding of the gap to fill and delineate the future research work needed to bring polyester‐based NPs closer to clinical application.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

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100 Years of Drug Delivery to the Lungs

Cited by 39 publications

References 41 publications

Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

Optimal Connection for Tiotropium SMI Delivery through Mechanical Ventilation: An In Vitro Study

Polyester nanoparticles delivering chemotherapeutics: Learning from the past and looking to the future to enhance their clinical impact in tumor therapy

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