Cited by 213Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryGlioma Diagnosis and Treatment

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Chemotherapeutic Drugs Released from Polymers: Distribution of 1,3-bis(2-chloroethyl)-l-nitrosourea in the Rat Brain

Fung, Lawrence K., Shin, Marian, Tyler, Betty, Brem, Henry, Saltzman, W. Mark·1996·Pharmaceutical Research

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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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Authors: Fung, L. K., Shin, M., Tyler, B., Brem, H., & Saltzman, W. M.
Affiliations: Johns Hopkins University (US)
ORCID: Fung, Lawrence K.
Tyler, Betty
Brem, Henry
Saltzman, W. Mark
Venue: Pharmaceutical Research
Publisher: Springer Science and Business Media LLC
Published: 1996-05
Volume: 13
Issue: 5
Pages: 671-682
ISSN: 0724-8741 (ISSN-L)
1573-904X
DOI: 10.1023/a:1016083113123
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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 › Oncology › 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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Chemotherapeutic Drugs Released from Polymers: Distribution of 1,3-bis(2-chloroethyl)-l-nitrosourea in the Rat Brain

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