Dept. of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Biotechnol Prog. 2011 Sep-Oct;27(5):1478-87. doi: 10.1002/btpr.665. Epub 2011 Jul 22.
Malignant gliomas are aggressive forms of primary brain tumors characterized by a poor prognosis. The most successful treatment so far is the local implantation of polymer carriers (Gliadel® wafers) for the sustained release of carmustine. To improve the effectiveness of local drug treatment, new polymer carriers and pharmacological agents are currently being investigated. Of particular interest is a set of novel thermo-gelling polymers for the controlled release of hydrophobic drugs such as paclitaxel (e.g., OncoGel™). Herein, we use computational mass transport simulations to investigate the effectiveness of paclitaxel delivery from hydrogel-forming polymer carriers. We found similar (within 1-2 mm) therapeutic penetration distances of paclitaxel when released from these hydrogels as compared with carmustine released from Gliadel® wafers. Effective therapeutic concentrations were maintained for >30 days for paclitaxel when released from the hydrogel as compared with 4 days for carmustine released from Gliadel® wafers. Convection in brain tissue prevented the formation of a uniform drug concentration gradient around the implant. In addition, the surface area to volume ratio of the gel is an important factor that should be considered to maintain a controlled release of paclitaxel within the degradation lifetime of the polymer matrix.
恶性胶质瘤是原发性脑肿瘤中侵袭性较强的一种，预后较差。迄今为止，最成功的治疗方法是局部植入聚合物载体（Gliadel® 片），以持续释放卡莫司汀。为了提高局部药物治疗的效果，目前正在研究新的聚合物载体和药理学制剂。一组新型的温敏聚合物特别受到关注，用于控制释放疏水性药物，如紫杉醇（例如 OncoGel™）。在此，我们使用计算质量传输模拟来研究从水凝胶形成聚合物载体中释放紫杉醇的效果。我们发现，与Gliadel® 片释放的卡莫司汀相比，这些水凝胶释放的紫杉醇具有相似的（在 1-2mm 范围内）治疗穿透距离。与 Gliadel® 片释放的卡莫司汀相比，当紫杉醇从水凝胶中释放时，有效治疗浓度可维持超过 30 天，而卡莫司汀仅能维持 4 天。脑组织中的对流阻止了在植入物周围形成均匀的药物浓度梯度。此外，凝胶的表面积与体积比是一个重要因素，应该考虑在内，以在聚合物基质的降解寿命内保持紫杉醇的控释。
