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Morphological Characterization of Polyanhydride Biodegradable Implant Gliadel® During in Vitro and in Vivo Erosion Using Scanning Electron Microscopy

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Abstract

Purpose. The objectives of the current study are to characterize the distribution of the chemotherapeutic agent carmustine (BCNU) in spray dried polyanhydride microspheres and to describe the morphological changes that occur during the in vitro and in vivo erosion of the polyanhydride implant-GLIADEL®, which consists of BCNU distributed in the copolymer matrix of poly(carboxyphenoxy propane:sebacic acid) in a 20:80 molar ratio (p(CPP:SA, 20:80)).

Methods. Scanning electron microscopy (SEM) was used to visualize the morphological changes of the polymer during the manufacturing process and in vitro and in vivo erosion.

Results. This study revealed that BCNU was homogeneously distributed within spray dried polyanhydride microspheres with no phase separation. The porosity of the wafer fabricated from spray dried polyanhydride microspheres gradually increased during erosion. During the initial period following wafer implantation in the brains of rats, erosion was mainly confined to the surface layer of the wafer with the majority of the wafer remaining intact. The eroding front gradually advanced from the surface to the interior of the wafer in a layerwise fashion, creating pores and connecting channel. Eventually both the interior and exterior of the wafers were eroded and the same porous structure was seen throughout the whole wafer.

Conclusions. This study provides the first visual observation of the morphological changes of the GLIADEL® wafer during erosion of the polyanhydride matrix and release of the drug substance BCNU. The observations in this study support the conclusion that BCNU release from a polyanhydride wafer is controlled both by diffusion of the drug and erosion of the polymer matrix.

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REFERENCES

  1. H. Brem, M. Mahaley, N. Vick, K. Black, S. Schold, P. Burger, A. Friedman, I. Ciric, T. Eller, J. Cozzens and J. Kenealy. Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. Journal of Neurosurgery 74:441–446 (1991).

    Google Scholar 

  2. H. Brem, S. Piantadosi, P. Burger, M. Walker, R. Selker, N. Vick, K. Black, M. Sisti, S. Brem, G. Mohr, P. Muller, R. Morawetz and S. Schold. Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Lancet 345:1008–1012 (1995).

    Google Scholar 

  3. M. Chasin, D. Lewis and R. Langer. Polyanhydrides for controlled drug delivery. Biopharm. Manufacturing 1:33–46 (1988).

    Google Scholar 

  4. S. Valtonen, G. Unsgaard, L. Kivipelto, O. Heiskanen and T. Kuurne, Placebo-controlled trial of GLIADEL placement at the time of first surgery for malignant glioma, in Eleventh International Conference on Brain Tumor Research and Therapy 1995: Napa, California.

  5. M. Chasin, G. Hollenbeck, H. Brem, S. Grossman, M. Colvin and R. Langer. Interstitial drug therapy for brain tumors: A case study. Drug Development and Industrial Pharmacy 16:2579–2594 (1990).

    Google Scholar 

  6. E. Mathiowitz, J. Jacob, K. Pekarek and D. Chickering III. Morphological characterization of bioerodible polymers. 3. Characterization of the erosion and intact zones in polyanhydrides using scanning electron microscopy. Macromolecules 26:6766–6765 (1993).

    Google Scholar 

  7. E. Mathiowitz, H. Bernstein, S. Giannos, P. Dor, T. Turek and R. Langer. Polyanhydride microspheres. IV. Morphology and Characterization of Systems Made by Spray Drying. Journal of Applied Polymer Science 45:125–134 (1992).

    Google Scholar 

  8. E. Mathiowitz, C. Amato, P. Dor and R. Langer. Polyanhydride microspheres: 3. Morphology and characterization of systems made by solvent removal. Polymer 31:547–555 (1990).

    Google Scholar 

  9. E. Mathiowitz, D. Kline and R. Langer. Morphology of polyanhydride microsphere delivery systems. Scanning microscopy 4:329–340 (1990).

    Google Scholar 

  10. A. Domb, S. Amselem, J. Shah and M. Maniar. Polyanhydrides: Synthesis and characterization. Advances in Polymer Sciences 107:94–141 (1993).

    Google Scholar 

  11. C. S. Reinhard, M. L. Radomsky, W. M. Saltzman, J. Hilton and H. Brem. Polymeric controlled release of dexamethasone in normal rat brain. Journal of Controlled Release 16:331–340 (1991).

    Google Scholar 

  12. E. Mathiowitz, W. M. Saltzman, A. Domb, P. Dor and R. Langer. Polyanhydride microspheres as drug carriers. II. Microencapsulation by solvent removal. Journal of Applied Polymer Science 35:755–774 (1988).

    Google Scholar 

  13. W. Dang and T. Daviau et. al. The effect of GLIADEL wafer initial molecular weight on the erosion of wafer and release of BCNU. Journal of Controlled Release (in press).

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Dang, W., Daviau, T. & Brem, H. Morphological Characterization of Polyanhydride Biodegradable Implant Gliadel® During in Vitro and in Vivo Erosion Using Scanning Electron Microscopy. Pharm Res 13, 683–691 (1996). https://doi.org/10.1023/A:1016035229961

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  • DOI: https://doi.org/10.1023/A:1016035229961

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