Chemotherapeutic Drugs Released from Polymers: Distribution of 1,3-bis(2-chloroethyl)-l-nitrosourea in the Rat Brain
Abstract
Purpose The distribution of [(3)H]BCNU following release from polymer implants in the rat brain was measured and evaluated by using mathematical models. Methods [(3)H]BCNU was loaded into p(CPP:SA) pellets, which were subsequently implanted intracerebrally in rats; [(3)H]BCNU was also directly injected into the brains of normal rats and rats with intracranially transplanted 9L gliomas. Concentrations of [(3)H]BCNU on coronal sections of the brain were measured by autoradiography and image processing. For comparison, the kinetics of [(3)H]BCNU release from the p(CPP:SA) polymer discs into phosphate-buffered saline were also measured. Results High concentrations of BCNU (corresponding to 1 mM) were measured near the polymer for the entire 30-day experiment. The penetration distance, defined as the distance from the polymer surface to the point where the concentration of [(3)H]BCNU in the tissue had dropped to 10 percent of the maximum value, was determined: penetration distance was 5 mm at day 1 and 1 mm at days 3 through 14. Local concentration profiles were compared with a mathematical model for estimation of the modulus phi (2), an indicator of the relative rate of elimination to diffusion in the brain. From day 3 to 14, phi(2) was 7, indicating that BCNU elimination was rapid compared to the rate of diffusive penetration into tissue. The enhanced penetration observed on day 1 appears to be due to convection of extracellular fluid caused by transient, vasogenic edema, which…
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Direct CNS administration is limited by diffusion distance and rapid efflux of drugs out of the CNS within hours.
“However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [8]
Direct CNS administration is invasive and may cause infection and tissue damage.
“However, direct CNS administration is invasive, which may cause infection and tissue damage, and is also limited by diffusion distance and rapid efflux of drugs out of the CNS within hours (8–10).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [8]
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- Authors
- Fung, L. K., Shin, M., Tyler, B., Brem, H., & Saltzman, W. M.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Pharmaceutical Research
- Published
- 1996-05
- Volume
- 13
- Issue
- 5
- Pages
- 671-682
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W205461530
- Cited by
- 213
- References
- 34
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 7 · 2019: 12 · 2018: 13 · 2017: 10 · 2016: 15 · 2015: 12 · 2014: 11 · 2013: 10 · 2012: 12
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1u01ca052857-01)
- National Cancer Institute (U01-CA 52857)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- 1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU, brain drug distribution, polymer implants, controlled drug release, 9L glioma, intracerebral implantation, penetration depth, drug elimination kinetics, convection, vasogenic edema, mathematical modeling of drug release
- MeSH terms
- Animals, Autoradiography, Brain, Carmustine, Drug Carriers, Male, Microinjections, Polymers, Rats, Inbred F344, Tritium, Antineoplastic Agents, Alkylating, Rats
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