Targeted drug nanocrystals for pulmonary delivery: a potential strategy for lung cancer therapy

ABSTRACT

Introduction

Lung cancer and metastases are major concerns worldwide. Although systemic chemotherapy is the recommended treatment, it is associated with various disadvantages, including nonselective drug distribution and systemic toxicity. In contrast, the pulmonary route ensures the localized delivery of drugs to the lung. Still, the pulmonary route is prone to clearance, limited drug dissolution, and local toxicity to healthy lung cells. Drug nanocrystals provide a potential strategy to enhance the therapeutic efficacy and mitigate the limitations of pulmonary delivery.

Areas covered

The development and potential application of nanocrystals in pulmonary delivery, their role in overcoming associated barriers, and strategies for site-specific and stimuli-responsive pulmonary delivery are outlined. This review also traces different in-vitro pulmonary models for assessments of the performance of drug nanocrystals and nanocrystals loaded carriers in pulmonary delivery.

Expert opinion

Enhanced stability, high aerosolization performance, better particle size distribution, improved penetration, sustained release of the drug, and minimal excipients usage makes drug nanocrystal an ideal candidate for pulmonary delivery. Besides, drug nanocrystals may provide selective cellular internalization with minimum clearance and maximum deposition. Furthermore, surface modified nanocrystals and nanocrystals in nanocarriers can exhibit a more prolonged, and site-specific release of the drug to cancer cells in the lungs.

KEYWORDS:

• Drug nanocrystals
• pulmonary Delivery
• targeted nanocrystals
• lung cancer

Article highlights

• Currently, anti-cancer drugs and formulations are administered by systemic routes in lung cancer therapy. However, pulmonary delivery may be a safer and more efficient alternative, reducing the dose due to more selective distribution and minimizing the toxicity to healthy cells.

• Drug nanocrystals offer certain advantages like increased solubility and stability, with minimal use of excipients (A major concern while developing formulation for pulmonary administration).

• The advances in targeted delivery, tumor microenvironment responsive systems, and delivery systems releasing drugs on external stimuli, ensures a more precise and selective drug delivery.

• The evidence although limited, of pulmonary delivery of nanocrystals and nanocrystal loaded carriers with enhanced aerosolization, in-vitro, and in-vivo performances will be suggest the potential use of this platform for localized lung cancer therapy.

• As of now the lack of mechanistic evidence of the fate of nanocrystals in pulmonary fluid, in-vitro models mimicking the respiratory system for evaluation of the performance of the formulation and inefficient in-vivo models are few of the drawbacks limiting the translational progress of this approach.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.