Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors

Title
Hyaluronic acid-based hydrogel for regional delivery of paclitaxel to intraperitoneal tumors
Authors
Gaurav BajajMi Ran KimSulma I. Mohammed여윤
Keywords
Intraperitoneal; Paclitaxel; Hydrogel; Particles; Drug delivery
Issue Date
2012-03
Publisher
Journal of controlled release
Citation
VOL 158, NO 3, 386-392
Abstract
Intraperitoneal (IP) chemotherapy is an effective way of treating local and regional malignancies confined in the peritoneal cavity such as ovarian cancer. However, a persistent major challenge in IP chemotherapy is the need to provide effective drug concentrations in the peritoneal cavity for an extended period of time. We hypothesized that hyaluronic acid (HA)-based in-situ crosslinkable hydrogel would serve as a carrier of paclitaxel (PTX) particles to improve their IP retention and therapeutic effects. In-vitro gel degradation and release kinetics studies demonstrated that HA gels could entrap microparticulate PTX (>100 μm) and release the drug over 10 days, gradually degraded by hyaluronidase, but had limited effect on retention of Taxol, a 14-nm micelle form of PTX. When administered IP to tumor-bearing nude mice, PTX was best retained in the peritoneal cavity as PTX-gel (microparticulate PTX entrapped in the HA gel), whereas Taxol-gel and other Taxol-based formulations left negligible amount of PTX in the cavity after 14 days. Despite the increase in IP retention of PTX, PTX-gel did not further decrease the tumor burdens than Taxol-based formulations, presumably due to the limited dissolution of PTX. This result indicates that spatial availability of a drug does not necessarily translate to the enhanced anti-tumor effect unless it is accompanied by the temporal availability.
URI
http://pubs.kist.re.kr/handle/201004/44080
ISSN
01683659
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KIST Publication > Article
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