HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Meng, W. Articles by Garnett, M. C. Search for Related Content PubMed PubMed Citation Articles by Meng, W. Articles by Garnett, M. C.

---

ORIGINAL RESEARCH ARTICLE

Evaluation of Poly (Glycerol-Adipate) Nanoparticle Uptake in an In Vitro 3-D Brain Tumor Co-Culture Model

W. Meng^*,1, P. Kallinteri^*,2, D. A. Walker, T. L. Parker and M. C. Garnett^*,3

^* School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, United Kingdom; School of Human Development, Queen’s Medical Centre, Nottingham, NG7 2UH, United Kingdom; and School of Biomedical Science, University of Nottingham, Nottingham, NG7 2RD, United Kingdom

To whom requests for reprints should be addressed at ³ Boots Building, University Park, Nottingham, Nottinghamshire NG7 2RD, United Kingdom. E-mail: martin.garnett@nottingham.ac.uk

Despite the inherent problems associated with in vivo animal models of tumor growth and metastases, many of the current in vitro brain tumor models also do not accurately mimic tumor-host brain interactions. Therefore, there is a need to develop such co-culture models to study tumor biology and, importantly, the efficacy of drug delivery systems targeting the brain. So far, few investigations of this nature have been published. In this paper we describe the development of a new model system and its application to drug delivery assessment. For our new model, a co-culture of DAOY cell brain tumor aggregates and organo-typic brain slices was developed. Initially, the DAOY aggregates attached to cerebellum slices and invaded as a unit. Single cells in the periphery of the aggregate detached from the DAOY aggregates and gradually replaced normal brain cells. This invasive behavior of DAOY cells toward organotypic cerebellum slices shows a similar pattern to that seen in vivo. After validation of the co-culture model using transmission electron microscopy, nanoparticle (NP) uptake was then evaluated. Confocal micrographs illustrated that DAOY cells in this co-culture model took up most of the NPs, but few NPs were distributed into brain cells. This finding corresponded with results of NP uptake in DAOY and brain aggregates reported elsewhere.

Key Words: biodegradable nanoparticles • medulloblastoma • organotypic culture