Lapatinib nano-delivery systems: a promising future for breast cancer treatment

ABSTRACT

Introduction: Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation.

Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose.

Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.

KEYWORDS:

• Active targeting
• capecitabine
• letrozole
• nano-delivery system
• passive targeting
• tyrosine kinase

Article highlights

• Lapatinib is a targeted dual tyrosine kinase inhibitor of EGFR and HER2, overexpressed by tumor cells of BC.

• Its clinical use is limited due to its poor aqueous solubility, poor bioavailability, high binding affinity toward blood proteins, and toxicities related to its higher dose. Also, stability and scale-up issues also contribute to the commercial availability of nano-delivery systems

• Nano-delivery system could serve as a promising alternative by virtue of its benefits like easy surface modification for active targeting and longer circulation half-life, passive targeting via enhanced permeation and retention effect.

• Various nano-delivery systems, including nanoparticles, polymeric micelle, core-shell nanoparticles, nanochannel, etc., were investigated for lapatinib delivery and summarized in the present review.

• On the other hand, owing to its exclusive selectivity to abovementioned receptors, they are employed as diagnostic agents for detection of BC through its conjugate with imaging agents.

• Lapatinib also reported to have multidrug resistant reversal property, which could be exploited to treat resistant cancer by its novel combination with paclitaxel.

• It could be suggested that the scale-up and technology transfer techniques should be revised and modified in light of manufacturing of nano-delivery systems of lapatinib, for commercial level production.

This box summarizes key points contained in the article.

Acknowledgments

The authors are thankful to Ministry of Human Resources and Development, New Delhi (India) and Department of Pharmaceutical Engineering & Technology, IIT (BHU), Varanasi (U.P., India) for providing financial assistance.

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

Author contributions

GV Bonde collected all the literature for this review and both edited and prepared the manuscript for submission. B Mishra provided guidance for the collection of literature information and manuscript editing. SK Yadav provided guidance for arrangement of collected literature information. S Chauhan and P Mittal assisted in language and paragraph editing. G Ajmal assisted in the overall editing of the manuscript as per journal guidelines. S Thokala assisted in editing references as per journal guidelines.

Additional information

Funding

This paper was not funded.