Three weeks release BCNU loaded hydrophilic-PLGA microspheres for interstitial chemotherapy: Development and activity against human glioblastoma cells

Authors: Esther Gil-Alegre, Maria; Gonzalez-Alvarez, Isabel; Gutierrez-Pauls, Laura; Torres-Suarez, Ana Isabel

Source: Journal of Microencapsulation, Volume 25, Number 8, 2008 , pp. 561-568(8)

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Abstract:

The aim of this study is the development of microspheres of BCNU for intracranial administration, as an alternative to marketed novel Gliadel® Implant in the treatment of brain tumours. H poly-lactide-co-glycolide biodegradable microspheres of BCNU with a mean size of 33.5 ± 1.8 µm were obtained by an oil-in-water emulsion solvent evaporation method. Their small size would allow their intracranial administration through a needle by cerebral stereotaxia if tumour recurrence occurs, without a surgical intervention, as Gliadel® needs. BCNU was released from these microspheres during 21 days, mainly by a mechanism of diffusion from the polymer matrix (K = 2.91 mg days-½). The cytotoxic effects of these microspheres on human glioblastoma cells were demonstrated all through 21 days and the value of percentage of viable cells was less than 40%. These microspheres should be commercialized as a freeze-dried product to keep at -20°C. Three hundred and twenty milligrams of microspheres contain 61.6 mg of BCNU, the same amount of BCNU contained in 1600 mg or eight wafers of Gliadel usually implanted after the tumour resection.

Keywords: BCNU; H-poly(D,L-lactide-co-glycolide); biodegradable microspheres; brain tumours; interstitial chemotherapy

Document Type: Research article

DOI: http://dx.doi.org/10.1080/02652040802075799

Affiliations: 1: Department of Pharmacy and Pharmaceutical Technology, Complutense University of Madrid, Spain

Publication date: 2008-01-01

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