Abstract
Despite advances in chemotherapeutic regimens, the treatment of metastatic cancer remains a challenge. A key problem with chemotherapy drugs is nonspecific drug distribution, resulting in low tumor concentrations and systemic toxicity. The holy grail of clinical cancer research has been to establish more specific ways of directing therapeutics to tumors, whether through more targeted anti-cancer agents or via the method of delivery. Many tumor cells show upregulated expression of receptors for the polysaccharide hyaluronan (HA), resulting in HA having a high affinity for tumors. This observation has led to the preclinical development of HA-cytotoxin bioconjugates that utilize HA as the tumor recognition moiety. The primary challenges have been organ-directed toxicity and limited efficacy. An alternative, simpler strategy has been to use the large volumetric domain of HA to entrain small chemotherapeutic drugs within the HA matrix. The resultant HA/drug formulation accumulates in the microvascular of the tumor, forming a microembolism that increases drug retention at the tumor site and allows for active tumor uptake through HA receptors. Clinical trials of HA formulations of three anti-cancer drugs have been undertaken and have demonstrated that such formulations are safe and efficacious. Within these formulations we postulate that HA is acting as a novel excipient, capable of improving the therapeutic index of the active anti-cancer agent.
Keywords: Hyaluronic acid, CD44, drug delivery, excipient, chemotherapy
Current Pharmaceutical Biotechnology
Title: The Development of Hyaluronan as a Drug Transporter and Excipient for Chemotherapeutic Drugs
Volume: 9 Issue: 4
Author(s): Tracey J. Brown
Affiliation:
Keywords: Hyaluronic acid, CD44, drug delivery, excipient, chemotherapy
Abstract: Despite advances in chemotherapeutic regimens, the treatment of metastatic cancer remains a challenge. A key problem with chemotherapy drugs is nonspecific drug distribution, resulting in low tumor concentrations and systemic toxicity. The holy grail of clinical cancer research has been to establish more specific ways of directing therapeutics to tumors, whether through more targeted anti-cancer agents or via the method of delivery. Many tumor cells show upregulated expression of receptors for the polysaccharide hyaluronan (HA), resulting in HA having a high affinity for tumors. This observation has led to the preclinical development of HA-cytotoxin bioconjugates that utilize HA as the tumor recognition moiety. The primary challenges have been organ-directed toxicity and limited efficacy. An alternative, simpler strategy has been to use the large volumetric domain of HA to entrain small chemotherapeutic drugs within the HA matrix. The resultant HA/drug formulation accumulates in the microvascular of the tumor, forming a microembolism that increases drug retention at the tumor site and allows for active tumor uptake through HA receptors. Clinical trials of HA formulations of three anti-cancer drugs have been undertaken and have demonstrated that such formulations are safe and efficacious. Within these formulations we postulate that HA is acting as a novel excipient, capable of improving the therapeutic index of the active anti-cancer agent.
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Cite this article as:
Brown J. Tracey, The Development of Hyaluronan as a Drug Transporter and Excipient for Chemotherapeutic Drugs, Current Pharmaceutical Biotechnology 2008; 9 (4) . https://dx.doi.org/10.2174/138920108785161514
DOI https://dx.doi.org/10.2174/138920108785161514 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
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