In situ forming PLGA implant for 90 days controlled release of leuprolide acetate for treatment of prostate cancer |
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| Authors: | Marjan Enayati Hamid Mobedi Shahriar Hojjati‐Emami Hamid Mirzadeh Milad Jafari‐Nodoushan |
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| Affiliation: | 1. Department of Biomedical Research, Medical University of Vienna, Vienna, Austria;2. Department of Biomedical Engineering, Tehran Polytechnique University, Tehran, Iran;3. Novel Drug Delivery Systems Department, Iran Polymer and Petrochemical Institute, Tehran, Iran |
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| Abstract: | In prostate cancer, hormone therapy via leuprolide acetate drug (LUP) is used to lower the level of testosterone down to castration level to effectively control the development of prostate cancer. The objective of this study was to evaluate the effective parameters in degradation and controlled release of an injectable in situ formed polymeric implant, loaded with leuprolide acetate, in order to achieve an optimum formulation for sustained drug release for 90 days with minimum burst release. The main problem associating with such implants is their high burst release. Designing an injectable implant with sustained and minimum burst release has thus become an attractive challenge in drug delivery field. Effects of type of poly(lactic‐co‐glycolic acid) 75:25 copolymers (RG752, RG756) and addition of nano‐hydroxyapatite (HA) particles on degradation rates of the implants and release profiles were examined in vitro and in vivo in a rabbit animal model. Results showed that implants containing polymers with higher molecular weights had significantly lower weight loss and molecular weight reduction. Adding nanoparticles of hydroxyapatite into poly(lactic‐co‐glycolic acid) implants caused further reduction in degradation rates, leading to a more sustained drug release in vivo, with reduced burst release. Different conventional kinetic models were applied to drug release and degradation data. The degradation data fit well to the first‐order degradation model. Higuchi model was the best kinetic release model fitted to the experimental in vitro release data. This study led to an optimum formulation (RG756:RG752 3:1 + 5% HA) with sustained leuprolide release and testosterone suppression over a 90‐day period with significant decrease of burst release phase (50%, p < 0.001) compared with the conventional Eligard formulation. The histopathology test showed that the formulated implant had no effects of toxicity or tissue necrosis in organs of the animal model. Copyright © 2017 John Wiley & Sons, Ltd. |
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| Keywords: | in situ forming drug delivery degradation poly (lactic‐co‐glycolic acid) burst release controlled release |
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