Publications by authors named "Deborah Schachter"

3 Publications

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Osteogenic activity of locally applied small molecule drugs in a rat femur defect model.

J Biomed Biotechnol 2010 16;2010:597641. Epub 2010 Jun 16.

Department of Biochemistry & Molecular Biology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

The long-term success of arthroplastic joints is dependent on the stabilization of the implant within the skeletal site. Movement of the arthroplastic implant within the bone can stimulate osteolysis, and therefore methods which promote rigid fixation or bone growth are expected to enhance implant stability and the long-term success of joint arthroplasty. In the present study, we used a simple bilateral bone defect model to analyze the osteogenic activity of three small-molecule drug implants via microcomputerized tomography (micro-CT) and histomorphometry. In this study, we show that local delivery of alendronate, but not lovastatin or omeprazole, led to significant new bone formation at the defect site. Since alendronate impedes osteoclast-development, it is theorized that alendronate treatment results in a net increase in bone formation by preventing osteoclast mediated remodeling of the newly formed bone and upregulating osteoblasts.
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http://dx.doi.org/10.1155/2010/597641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896701PMC
October 2010

Solid state NMR perspective of drug-polymer solid solutions: a model system based on poly(ethylene oxide).

Int J Pharm 2004 Aug;281(1-2):89-101

The Dow Chemical Company, 171 River Road, Piscataway, NJ 08854, USA.

Poly(ethylene oxide) (PEO) was tested as a polymer matrix for solid dispersion to enhance drug bioavailability. Solid state nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and transmission electron microscopy (TEM) were utilized to characterize the high miscibility between PEO and ketoprofen, a model for crystalline drugs with poor water solubility. The experimental data demonstrated that ketoprofen in the melt-processed blend formed a complete molecular dispersion within the amorphous domain of PEO, resulting in high molecular mobility of ketoprofen in the melt-processed blend that leads to enhanced dissolution rate of ketoprofen in aqueous media. Hydrogen bonds between the carboxylic group of ketoprofen and the ether oxygen of PEO, as detected by solid-state NMR, are the likely source for the high miscibility between ketoprofen and PEO. Such drug/polymer molecular interactions promote dispersion of ketoprofen into amorphous phase of PEO at temperatures well below melting points of both crystalline ketoprofen and PEO. Consequently, melt-processing temperatures can be reduced significantly to avoid thermal degradation. The processing conditions can be also flexible while maintaining reproducibility of the physico-chemical properties of the blend. Furthermore, the high degree of drug/polymer molecular interactions stabilizes the morphology of the blend during storage.
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http://dx.doi.org/10.1016/j.ijpharm.2004.05.024DOI Listing
August 2004

A synthetic polymer matrix for the delayed or pulsatile release of water-soluble peptides.

J Control Release 2002 Jan;78(1-3):143-53

Department of Chemistry, Rutgers-The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854, USA.

The design of a polymeric peptide release system with a controlled delay time and a burst-free pre-release phase is described. In general, the system consists of a blend of a tyrosine-derived polyarylate and a fast-degrading copolymer of lactic and glycolic acid (PLGA). Due to the peptide-like structure of the polyarylate backbone, peptide-polymer interactions prevented the release of peptide from neat polyarylate films. The addition of PLGA acts as a 'delayed' excipient: as PLGA degrades, it generates acidic degradation products that cause a drop in the internal pH of the polyarylate matrix. This drop in pH weakens the peptide-polymer interactions and causes the release of peptide to commence. The initial molecular weight of PLGA can be used to control the length of time before degradation occurs. Consequently, this parameter can also be used to control the duration of the delay period prior to peptide release. As a specific model system, blends of poly(DTH adipate) with three different copolymers of lactic and glycolic acid were prepared and used for the delayed release of Integrilin, a synthetic water-soluble heptapeptide (clinically used in antithrombic injections) that acts as a highly potent glycoprotein IIb/IIIa antagonist. Blends composed of a 1:1 weight ratio of poly(DTH adipate) and PLGA and containing Integrilin (15%, w/w) were prepared. In vitro release studies were conducted in phosphate buffered solution at 37 degrees C and the release of Integrilin was followed by HPLC. As the initial molecular weight of PLGA varied from 12000 to 62000, the duration of the delay period prior to release increased from 5 to 28 days.
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http://dx.doi.org/10.1016/s0168-3659(01)00487-4DOI Listing
January 2002