title: Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.
abstract: Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding 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 (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.
authors.affiliation: Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA ; Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Woodman
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Suh
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
authors.forename: Jianxing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, UConn Health, Farmington, CT 06030, USA.
authors.forename: Yuvabharath
authors.initials: Y
authors.lastname: Kondaveeti
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Burgess
authors.affiliation: Department of Cell Biology, UConn Health, Farmington, CT 06030, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: White
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
authors.forename: Glenn D
authors.initials: GD
authors.lastname: Prestwich
authors.affiliation: Department of Reconstructive Sciences, UConn Health, Farmington, CT 06030, USA.
authors.forename: Liisa T
authors.initials: LT
authors.lastname: Kuhn