Open Access Open Access  Restricted Access Subscription Access

Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery


Affiliations
1 Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, United States
2 Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States
3 Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, United States
4 Department of Cell Biology, UConn Health, Farmington, CT 06030, United States
5 Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, United States
 

Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative ofHAthat is recognized byHAbinding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units.These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/low human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drug cis-diamminedichloroplatinum (II) (CDDP) to form nCaPCMHACDDP. nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43mV zeta potential. nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaPCMHA-AF488 was taken up by CD44+/CD24 BT-474EMT breast cancer cellswithin 18 hours. nCaPCMHACDDPwas as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8mg/kg CDDP than a 7mg/kg dose nCaPCMHACDDP.This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.
User
Notifications
Font Size

Abstract Views: 57

PDF Views: 0




  • Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery

Abstract Views: 57  |  PDF Views: 0

Authors

Jessica L. Woodman
Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, United States
Min Sung Suh
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States
Jianxing Zhang
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, United States
Yuvabharath Kondaveeti
Department of Cell Biology, UConn Health, Farmington, CT 06030, United States
Diane J. Burgess
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States
Bruce A. White
Department of Cell Biology, UConn Health, Farmington, CT 06030, United States
Glenn D. Prestwich
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, United States
Liisa T. Kuhn
Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, United States

Abstract


Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative ofHAthat is recognized byHAbinding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units.These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/low human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drug cis-diamminedichloroplatinum (II) (CDDP) to form nCaPCMHACDDP. nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43mV zeta potential. nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaPCMHA-AF488 was taken up by CD44+/CD24 BT-474EMT breast cancer cellswithin 18 hours. nCaPCMHACDDPwas as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8mg/kg CDDP than a 7mg/kg dose nCaPCMHACDDP.This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.