ISSN:
1042-7147
Keywords:
Polyanhydrides
;
Pulmonary neoplasms
;
Mice
;
Chemotherapy
;
Cisplatin
;
BCNU
;
Chemistry
;
Polymer and Materials Science
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
,
Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
Notes:
Investigations were undertaken to determine whether anti-cancer drugs introduced locally into the lung using bioerodible polyanhydride microspheres as carriers would demonstrate both efficacy and reduced toxicity.BCNU (carmustine) and CDDP (cisplatin), loaded in polyanhydride microspheres, were administered to mice bearing either of two tumors selected for their affinity for the lung: the B16F10 melanoma and the recently established GL26F4 glioma. Following intravenous inoculation of these tumor cells, the number of metastatic foci formed in the lung follows a predictable time course and can readily be determined. Comparisons were made between the efficacy of microspheres introduced into the lung by intratracheal intubation (IT) and of those administered by intraperitoneal injection (IP). Administration of microspheres loaded either with BCNU or cisplatin reduced the detectable metastatic foci by 25-90% depending on the tumor load, both when administered IP and IT.Toxicity was assessed by flow cytometric analysis of bone marrow cellularity as well as by determination of mortality rates. Intratracheal administration of either cisplatin or BCNU reduced the deleterious systemic effects observed when the drug was administered by IP injection. This was seen at high drug levels, where significant mortality occurred only in animals given drug injections IP; and at lower levels where IP injection led to a reduction of bone marrow blast cells, while IT administration caused no detectable effect on marrow cellularity.Since local delivery of BCNU or cisplatin through bioerodible polyanhydride microspheres induces significantly less systemic damage while demonstrating efficacy equal to or exceeding that of IP injection, this mode of drug delivery warrants further and more detailed exploration. Moreover, the method may be applicable to the treatment of other chronic pulmonary pathologies.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/pat.1992.220030607
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