Drug delivery in leptomeningeal disease: Navigating barriers and beyond

Leptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Fur...

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Main Authors: Numair Arshad, Nupur Biswas, Jaya Gill, Santosh Kesari, Shashaanka Ashili
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Drug Delivery
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Online Access:https://www.tandfonline.com/doi/10.1080/10717544.2024.2375521
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author Numair Arshad
Nupur Biswas
Jaya Gill
Santosh Kesari
Shashaanka Ashili
author_facet Numair Arshad
Nupur Biswas
Jaya Gill
Santosh Kesari
Shashaanka Ashili
author_sort Numair Arshad
collection DOAJ
description Leptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Furthermore, the predominant phenotype; solid masses or freely floating cells, has altering implications on the effectiveness of drug delivery systems. The standard of care is the intrathecal delivery of chemotherapy drugs but it is associated with increased instances of treatment-related complications, low patient compliance, and suboptimal drug distribution. An alternative involves administering the drugs systemically, after which they must traverse fluid barriers to arrive at their destination within the leptomeningeal space. However, this route is known to cause off-target effects as well as produce subtherapeutic drug concentrations at the target site within the central nervous system. The development of new drug delivery systems such as liposomal cytarabine has improved drug delivery in leptomeningeal metastatic disease, but much still needs to be done to effectively target this challenging condition. In this review, we discuss about the anatomy of leptomeninges relevant for drug penetration, the conventional and advanced drug delivery methods for LMD. We also discuss the future directions being set by different clinical trials.
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spelling doaj-art-ace05960f5e4499f8f88ef50f5828ede2025-08-20T02:38:11ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642024-12-0131110.1080/10717544.2024.2375521Drug delivery in leptomeningeal disease: Navigating barriers and beyondNumair Arshad0Nupur Biswas1Jaya Gill2Santosh Kesari3Shashaanka Ashili4Rhenix Lifesciences, Hyderabad, Telangana, IndiaRhenix Lifesciences, Hyderabad, Telangana, IndiaCureScience, San Diego, California, USADepartment of Translational Neurosciences, Pacific Neuroscience Institute and Saint John’s Cancer Institute at Providence Saint John’s Health Center, Santa Monica, California, USACureScience, San Diego, California, USALeptomeningeal disease (LMD) refers to the infiltration of cancer cells into the leptomeningeal compartment. Leptomeninges are the two membranous layers, called the arachnoid membrane and pia mater. The diffuse nature of LMD poses a challenge to its effective diagnosis and successful management. Furthermore, the predominant phenotype; solid masses or freely floating cells, has altering implications on the effectiveness of drug delivery systems. The standard of care is the intrathecal delivery of chemotherapy drugs but it is associated with increased instances of treatment-related complications, low patient compliance, and suboptimal drug distribution. An alternative involves administering the drugs systemically, after which they must traverse fluid barriers to arrive at their destination within the leptomeningeal space. However, this route is known to cause off-target effects as well as produce subtherapeutic drug concentrations at the target site within the central nervous system. The development of new drug delivery systems such as liposomal cytarabine has improved drug delivery in leptomeningeal metastatic disease, but much still needs to be done to effectively target this challenging condition. In this review, we discuss about the anatomy of leptomeninges relevant for drug penetration, the conventional and advanced drug delivery methods for LMD. We also discuss the future directions being set by different clinical trials.https://www.tandfonline.com/doi/10.1080/10717544.2024.2375521Leptomeningeal diseaseneoplastic meningitisleptomeningesCNS metastasisIntrathecal chemotherapyLeptomeningeal metastasis 
spellingShingle Numair Arshad
Nupur Biswas
Jaya Gill
Santosh Kesari
Shashaanka Ashili
Drug delivery in leptomeningeal disease: Navigating barriers and beyond
Drug Delivery
Leptomeningeal disease
neoplastic meningitis
leptomeninges
CNS metastasis
Intrathecal chemotherapy
Leptomeningeal metastasis 
title Drug delivery in leptomeningeal disease: Navigating barriers and beyond
title_full Drug delivery in leptomeningeal disease: Navigating barriers and beyond
title_fullStr Drug delivery in leptomeningeal disease: Navigating barriers and beyond
title_full_unstemmed Drug delivery in leptomeningeal disease: Navigating barriers and beyond
title_short Drug delivery in leptomeningeal disease: Navigating barriers and beyond
title_sort drug delivery in leptomeningeal disease navigating barriers and beyond
topic Leptomeningeal disease
neoplastic meningitis
leptomeninges
CNS metastasis
Intrathecal chemotherapy
Leptomeningeal metastasis 
url https://www.tandfonline.com/doi/10.1080/10717544.2024.2375521
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AT jayagill drugdeliveryinleptomeningealdiseasenavigatingbarriersandbeyond
AT santoshkesari drugdeliveryinleptomeningealdiseasenavigatingbarriersandbeyond
AT shashaankaashili drugdeliveryinleptomeningealdiseasenavigatingbarriersandbeyond