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Drug penetration in pediatric brain tumors: Challenges and opportunities
Jenny P Patel1, Susan E Spiller2, Elizabeth D Barker1
1Department of Mechanical, Aerospace, and Biomedical Engineering, The University of Tennessee at Knoxville, Knoxville, Tennessee.
Abstract:
Larger clinical trial enrollments and a greater understanding of biological heterogeneity have led to improved survival rates for children diagnosed with brain tumors in the last 50 years. However, reducing long-term morbidities and improving survival rates of high-risk tumors remain major challenges. Chemotherapy can reduce tumor burden, but effective drug penetration at the tumor site is limited by barriers in the route of drug administration and within the tumor microenvironment. Bioavailability of drugs is impeded by the blood-brain barrier, plasma protein binding, and structural components by the tumor including the matrix and vasculature contributing to increased interstitial fluid pressure, hypoxia, and acidity. Designing drug delivery systems to circumvent these barriers could lead to improved drug penetration at the tumor site and reduce adverse systemic side effects. In this review, we expand on how systemic and local barriers limit drug penetration and present potential methods to enhance drug penetration in pediatric brain tumors.
Insights
Improving pediatric brain tumor survival requires overcoming drug delivery barriers. This review explores challenges and strategies for enhancing chemotherapy penetration to improve treatment outcomes for children with brain tumors.
Area of Science:
- Pediatric Oncology
- Neuro-Oncology
- Drug Delivery Systems
Background:
- Significant advancements in pediatric brain tumor survival over 50 years due to clinical trials and understanding heterogeneity.
- High-risk pediatric brain tumors and associated long-term morbidities remain critical challenges.
- Current chemotherapy efficacy is limited by poor drug penetration to the tumor site.
Purpose of the Study:
- To review systemic and local barriers limiting drug penetration in pediatric brain tumors.
- To present potential strategies for enhancing drug delivery to pediatric brain tumors.
Main Methods:
- Literature review of systemic and local barriers to drug delivery in pediatric brain tumors.
- Exploration of novel drug delivery systems and strategies to overcome these barriers.
Main Results:
- Systemic barriers include the blood-brain barrier and plasma protein binding.
- Tumor microenvironment barriers include interstitial fluid pressure, hypoxia, and acidity.
- Potential strategies involve designing advanced drug delivery systems to circumvent these impediments.
Conclusions:
- Enhanced drug penetration is crucial for improving treatment efficacy in pediatric brain tumors.
- Overcoming delivery barriers can lead to better tumor burden reduction and reduced systemic side effects.
- Development of targeted drug delivery systems holds promise for improved pediatric neuro-oncology outcomes.
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