Development of Poly(Lactide-Co-Glycolide) Microspheres for Controlled Release of Thymosin Beta-4 in the Heart

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Title: Development of Poly(Lactide-Co-Glycolide) Microspheres for Controlled Release of Thymosin Beta-4 in the Heart
Author: Thatcher, Jeffrey Edward
Abstract: Thymosin beta -4 is of great importance because it improves heart function after heart attack in animal models . In order to limit the number of interventions in Thymosin beta -4 therapy , a localized and controlled release formulation is necessary . Our goal was to generate controlled release microsphere formulations of poly (lactic -co -glycolic acid ) that overcame a common problem of burst -release and to establish a method to modulate the release rates between formulations . Burst -release is the rapid release of drug from the formulation occurring in the initial 24 hours of elution . This event causes undesirable loss and potentially toxic levels of therapeutic from the microsphere . Modulation of release is of particular importance in these studies because little is known regarding the therapeutic dose of Thymosin beta -4 in humans . A class of non -ionic surfactants , alkyl glucosides , were used as excipients in preparation of poly (lactic -co -glycolic acid ) double -emulsion microspheres for controlled release of the protein albumin or the peptide Thymosin beta -4 . We specifically chose octyl -glucopyranoside and decyl -glucopyranoside for their ability to stabilize the primary emulsion step during microsphere synthesis . We demonstrate that the addition of alkyl glucosides of differing hydrocarbon chain length can modulate the rate of protein and peptide release from these microspheres . In albumin formulations , octyl -glucopyranoside reduced overall release compared to decyl -glucopyranoside and formulations prepared without surfactant , whereas in TB4 formulations decyl -glucopyranoside reduced overall release . In albumin containing microspheres burst release was high in formulations that did not contain any surfactant , 23 % . Addition of decyl -glucopyranoside reduced burst release to 6 % while addition of octyl -glucopyranoside further reduced burst release to 3 % . Thin sections revealed smaller and more uniform internal porosity in microspheres containing surfactant , of which octyl -glucopyranoside porosity was less than decyl -glucopyranoside porosity . This difference in porosity corresponds with the reduction in initial burst release and overall release of albumin . With these surfactants we established a group of formulations with differing drug release rates . This research suggests that formulations containing Thymosin beta -4 can be beneficially used in future in vivo testing to determine a controlled release profile capable of generating a therapeutic response in ischemic heart disease . [Keywords : microsphere , thymosin , alkyl glucoside , emulsion , suractant , PLGA , heart]
URI: http : / /hdl .handle .net /2152 .5 /1007
Date: 2012-07-17

Citation

Development of Poly(Lactide-Co-Glycolide) Microspheres for Controlled Release of Thymosin Beta-4 in the Heart. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /1007 .

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