title: Paclitaxel delivery to brain tumors from hydrogels: a computational study.
abstract: 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.
authors.affiliation: Dept. of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Alexis J
authors.initials: AJ
authors.lastname: Torres
authors.forename: Charles
authors.initials: C
authors.lastname: Zhu
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
authors.forename: Susan
authors.initials: S
authors.lastname: Pannullo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004337:Drug Carriers; D006801:Humans; D020100:Hydrogels; D051379:Mice; D008962:Models, Theoretical; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D020100:Hydrogels; D017239:Paclitaxel