Inhalable Formulations for Pulmonary Delivery to Treat Non-small Cell Lung Cancer (NSCLC): Development and In-Vitro Efficacy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 7484

Special Issue Editors


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Guest Editor
College of Pharmacy, Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa, IA, USA
Interests: biomaterials; lipids; drug delivery; nanomedicines; cancer therapy; PTT; PDT
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Teva Pharmaceuticals, Salt Lake City, UT, USA
Interests: TD product development; drug delivery; malignant mesothelioma; lung cancer; pulmonary hypertension

Special Issue Information

Dear Colleagues,

Nowadays, inhalation therapy is receiving much attention among scientists and researchers as the preferred administration route for treating non-small cell lung cancer in addition to other airway diseases. Pulmonary drug delivery via oral inhalation represents a new attractive non-invasive administration route for cancer therapeutics. For successful pulmonary drug delivery, delivery devices such as a nebulizers/inhalers and the formulation of therapeutic agents play an important role. In recent years, significant progress has been made in the development of advanced devices, including a device for powder formulation. Inhalation therapy as well as dry powder formulation and design are currently in the limelight due to their stability, aerodynamic properties, and convenient mode of administration. To ensure successful delivery via oral inhalation, formulation into an appropriate inhalable dosage form with good stability is very important. It is also essential that the formulation is paired with a device that generates an aerosol of the appropriate particle/droplet size to ensure deposition into the desired area of the respiratory tract.

Lung cancers are conventionally treated using oral or intravenous anticancer medications. However, these routes of administration are not ideal, as the required drugs are systemically delivered rather than being targeted to the actual tumor site. Therefore, higher doses may also be needed to achieve sufficiently concentration of drug in the lungs for the treatment purpose, which may consequently cause more adverse effects. The administration route, amount of deposition in the lungs, and therapeutic efficacy of the formulation/drug play a vital role in the treatment process. Inhalation therapy may overcome these limitations, with the actual amount of drug required for the treatment being less because the drugs will be efficiently delivered into the lungs/airways as inhaled aerosols. Lower doses can then be used to attain relatively high local concentrations in the lungs.

This Special Issue will focus on recent advances in treating NSCLC via inhalable formulations.

Dr. ‪Nikesh Gupta‬
Dr. Nishant S. Kulkarni
Guest Editors

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Keywords

  • pulmonary drug delivery
  • inhalation
  • nebulizer
  • nanoformulations
  • biomaterials
  • lipids
  • dry powder
  • cancer therapy

Published Papers (3 papers)

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Research

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20 pages, 6057 KiB  
Article
Scalable Production and In Vitro Efficacy of Inhaled Erlotinib Nanoemulsion for Enhanced Efficacy in Non-Small Cell Lung Cancer (NSCLC)
by Gautam Chauhan, Xuechun Wang, Carol Yousry and Vivek Gupta
Pharmaceutics 2023, 15(3), 996; https://doi.org/10.3390/pharmaceutics15030996 - 20 Mar 2023
Cited by 7 | Viewed by 2098
Abstract
Non-small cell lung cancer (NSCLC) is a global concern as one of the leading causes of cancer deaths. The treatment options for NSCLC are limited to systemic chemotherapy, administered either orally or intravenously, with no local chemotherapies to target NSCLC. In this study, [...] Read more.
Non-small cell lung cancer (NSCLC) is a global concern as one of the leading causes of cancer deaths. The treatment options for NSCLC are limited to systemic chemotherapy, administered either orally or intravenously, with no local chemotherapies to target NSCLC. In this study, we have prepared nanoemulsions of tyrosine kinase inhibitor (TKI), erlotinib, using the single step, continuous manufacturing, and easily scalable hot melt extrusion (HME) technique without additional size reduction step. The formulated nanoemulsions were optimized and evaluated for their physiochemical properties, in vitro aerosol deposition behavior, and therapeutic activity against NSCLC cell lines both in vitro and ex vivo. The optimized nanoemulsion showed suitable aerosolization characteristics for deep lung deposition. The in vitro anti-cancer activity was tested against the NSCLC A549 cell line which exhibited 2.8-fold lower IC50 for erlotinib-loaded nanoemulsion, as compared to erlotinib-free solution. Furthermore, ex vivo studies using a 3D spheroid model also revealed higher efficacy of erlotinib-loaded nanoemulsion against NSCLC. Hence, inhalable nanoemulsion can be considered as a potential therapeutic approach for the local lung delivery of erlotinib to NSCLC. Full article
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22 pages, 1820 KiB  
Review
Lipid-Based Inhalable Micro- and Nanocarriers of Active Agents for Treating Non-Small-Cell Lung Cancer
by Sona Gandhi and Indrajit Roy
Pharmaceutics 2023, 15(5), 1457; https://doi.org/10.3390/pharmaceutics15051457 - 10 May 2023
Cited by 3 | Viewed by 2032
Abstract
Non-small-cell lung cancer (NSCLC) afflicts about 2 million people worldwide, with both genetic (familial) and environmental factors contributing to its development and spread. The inadequacy of currently available therapeutic techniques, such as surgery, chemotherapy, and radiation therapy, in addressing NSCLC is reflected in [...] Read more.
Non-small-cell lung cancer (NSCLC) afflicts about 2 million people worldwide, with both genetic (familial) and environmental factors contributing to its development and spread. The inadequacy of currently available therapeutic techniques, such as surgery, chemotherapy, and radiation therapy, in addressing NSCLC is reflected in the very low survival rate of this disease. Therefore, newer approaches and combination therapy regimens are required to reverse this dismal scenario. Direct administration of inhalable nanotherapeutic agents to the cancer sites can potentially lead to optimal drug use, negligible side effects, and high therapeutic gain. Lipid-based nanoparticles are ideal agents for inhalable delivery owing to their high drug loading, ideal physical traits, sustained drug release, and biocompatibility. Drugs loaded within several lipid-based nanoformulations, such as liposomes, solid-lipid nanoparticles, lipid-based micelles, etc., have been developed as both aqueous dispersed formulations as well as dry-powder formulations for inhalable delivery in NSCLC models in vitro and in vivo. This review chronicles such developments and charts the future prospects of such nanoformulations in the treatment of NSCLC. Full article
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34 pages, 4075 KiB  
Review
Inhalable Formulations to Treat Non-Small Cell Lung Cancer (NSCLC): Recent Therapies and Developments
by Chetna Gupta, Aadya Jaipuria and Nikesh Gupta
Pharmaceutics 2023, 15(1), 139; https://doi.org/10.3390/pharmaceutics15010139 - 31 Dec 2022
Cited by 8 | Viewed by 2421
Abstract
Cancer has been the leading cause of mortalities, with lung cancer contributing 18% to overall deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The primary form of therapy used to treat lung cancer still includes oral and [...] Read more.
Cancer has been the leading cause of mortalities, with lung cancer contributing 18% to overall deaths. Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. The primary form of therapy used to treat lung cancer still includes oral and systemic administration of drugs, radiotherapy, or chemotherapy. Some patients have to go through a regime of combination therapy. Despite being the only available form of therapy, their use is limited due to the adverse effects, toxicity, and development of resistance over prolonged use. This led to a shift and progressive evolution into using pulmonary drug delivery systems. Being a non-invasive method of drug-administration and allowing localized delivery of drugs to cancer cells, inhalable drug delivery systems can lead to lower dosing and fewer systemic toxicities over other conventional routes. In this way, we can increase the actual local concentration of the drug in lungs, which will ultimately lead to better antitumor therapy. Nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening, and tracking. Regardless of the advantages, pulmonary delivery is still in the early stages of development and various factors such as pharmacology, immunology, and toxicology should be taken into consideration for the development of suitable inhalable nano-based chemotherapeutic drugs. They face numerous physiological barriers such as lung retention and efficacy, and could also lead to toxicity due to prolonged exposure. Nano-carriers with a sustained drug release mechanism could help in overcoming these challenges. This review article will focus on the various inhalable formulations for targeted drug delivery, including nano-based delivery systems such as lipids, liposome, polymeric and inorganic nanocarriers, micelles, microparticles and nanoaggregates for lung cancer treatment. Various devices used in pulmonary drug delivery loaded on various nano-carriers are also discussed in detail. Full article
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