PMID- 10469900
OWN - NLM
STAT- MEDLINE
DCOM- 19991013
LR  - 20190915
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 61
IP  - 1-2
DP  - 1999 Aug 27
TI  - The delivery of BCNU to brain tumors.
PG  - 21-41
AB  - This paper reports the development of three-dimensional simulations to study the 
      effect of various factors on the delivery of 1-3-bis(2-chloroethyl)-1-nitrosourea 
      (BCNU) to brain tumors. The study yields information on the efficacy of various 
      delivery methods, and the optimal location of polymer implantation. Two types of 
      drug deliveries, namely, systemic administration and controlled release from 
      polymers, were simulated using fluid dynamics analysis package (FIDAP) to predict 
      the temporal and spatial variation of drug distribution. Polymer-based delivery 
      provides higher mean concentration, longer BCNU exposure time and reduced 
      systemic toxicity than bolus injection. Polymer implanted in the core gives 
      higher concentration of drug in both the core and viable zone than the polymer in 
      the viable zone case. The penetration depth of BCNU is very short. This is 
      because BCNU can get drained out of the system before diffusing to any 
      appreciable distance. Since transvascular permeation is the dominant means of 
      BCNU delivery, the interstitial convection has minor effect because of the 
      extremely small transvascular Peclet number. The reaction of BCNU with brain 
      tissues reduces the drug concentration in all regions and its effect increases 
      with rate constant. The implantation of BCNU/ethylene-vinyl acetate copolymer 
      (EVAc) matrix at the lumen of the viable zone immediately following the surgical 
      removal of 80% of the tumor may be an effective treatment for the chemotherapy of 
      brain tumors. The present study provides a quantitative examination on the 
      working principle of Gliadel wafer for the treatment of brain tumors.
FAU - Wang, C C
AU  - Wang CC
AD  - Department of Chemical Engineering, National University of Singapore, 10 Kent 
      Ridge Crescent, Singapore, Singapore. chewch@nus.edu.sg
FAU - Li, J
AU  - Li J
FAU - Teo, C S
AU  - Teo CS
FAU - Lee, T
AU  - Lee T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - U68WG3173Y (Carmustine)
SB  - IM
MH  - Antineoplastic Agents, Alkylating/*administration & dosage
MH  - Brain Neoplasms/*drug therapy
MH  - Capillary Permeability
MH  - Carmustine/*administration & dosage/pharmacokinetics
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Models, Biological
EDAT- 1999/09/02 00:00
MHDA- 1999/09/02 00:01
CRDT- 1999/09/02 00:00
PHST- 1999/09/02 00:00 [pubmed]
PHST- 1999/09/02 00:01 [medline]
PHST- 1999/09/02 00:00 [entrez]
AID - S016836599900098X [pii]
AID - 10.1016/s0168-3659(99)00098-x [doi]
PST - ppublish
SO  - J Control Release. 1999 Aug 27;61(1-2):21-41. doi: 10.1016/s0168-3659(99)00098-x.