Mechanisms of antiproliferative drug release from bioresorbable porous structures.
Restenosis (renarrowing of the blood vessel wall) and cancer are two different pathologies that have drawn extensive research attention over the years. Antiproliferative drugs such as paclitaxel inhibit cell proliferation and are therefore effective in the treatment of cancer as well as neointimal hyperplasia, which is known to be the main cause of restenosis. Antiproliferative drugs are highly hydrophobic and their release from porous biodegradable structures is therefore advantageous. The release profiles of four antiproliferative drugs from highly porous polymeric structures were studied in this study in light of the physical properties of both the host polymers and the drug molecules, and a qualitative model was developed. The chemical structure of the polymer chain directly affects the drug release profile through water uptake in the early stages or degradation and erosion in later stages. It also affects the release profile indirectly, through the polymer's 3D porous structure. However, this effect is minor. The drug volume and molecular area dominantly affect its diffusion rate from the 3D porous structure and the drug's solubility parameter compared with that of the host polymer has some effect on the drug release profile. This model can also be used to describe release mechanisms of other hydrophobic drugs from porous structures.
Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.
Amir
A
Kraitzer
David
D
Alperstein
Yoel
Y
Kloog
Meital
M
Zilberman
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry; D054855:Drug-Eluting Stents; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D016062:Porosity; D012459:Salicylates / Q000008:administration & dosage* / Q000737:chemistry; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D011098:Polyglactin 910; D005204:Farnesol; D017239:Paclitaxel; D020123:Sirolimus