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• W1599002846 abstract "Abstract : Active targeting with controlled delivery of therapeutic agents to bone is an ideal approach for treatment of several bone diseases. Since bisphosphonates (BPs) have high affinity to bone mineral and are used in treatment of osteoporosis, they are well-suited for drug targeting to bone. For this purpose bifunctional hydrazine-bisphosphonates (HBPs) with spacers of various lengths and lipophilicity were synthesized and studied. Crystal growth inhibition assays demonstrated that the HBPs with shorter spacers bound more strongly to bone mineral, hydroxyapatite (HA), than did alendronate. HBPs were also demonstrated to be non-toxic to MC3T3-E1 pre-osteoblasts. Targeted delivery of the HBP-conjugated model drug, 4- nitrobenzaldehyde, was demonstrated through hydrolysis of the hydrazone linkage at the low pH of bone resorption and wound healing sites. In other experiments, a method to orient proteins on HA surfaces was developed to improve protein bioactivity. Enhanced green fluorescent protein (EGFP) and Beta-lactamase were used as model proteins. These proteins have a Ser or Thr at their Nterminus which was oxidized to obtain a single aldehyde group that was subsequently used for bonding HBPs of various length and lipophilicity through formation of a hydrazone bond. The amount of protein immobilized through various HBPs was determined and found not to be exclusively dependent on the length of HBPs. The enzymatic activity of HBP-immobilized Beta-lactamase, measured with cefazolin as substrate, was found to be higher than Beta-lactamase that was simply adsorbed on HA. In a third set of studies, HBPs were evaluated for delivering parathyroid hormone (PTH) to bone mineral to enhance cell responses for bone formation. PTH was oxidized and conjugated to HBPs, followed by targeting to bone wafers. In vitro bioassays demonstrated that HBP-targeted PTH stimulated greater synthesis of cAMP in preosteoblasts compared to surfaces with simply adsorbed PTH." @default.
• W1599002846 created "2016-06-24" @default.
• W1599002846 creator A5025836527 @default.
• W1599002846 date "2012-01-13" @default.
• W1599002846 modified "2023-09-26" @default.
• W1599002846 title "BIFUNCTIONAL BISPHOSPHONATES FOR DELIVERING BIOMOLECULES TO BONE" @default.
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