Effects of polymer chemistry, concentration, and pH on doxorubicin release kinetics from hydroxyapatite-PCL-PLGA composi
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Effects of polymer chemistry, concentration, and pH on doxorubicin release kinetics from hydroxyapatite-PCLPLGA composite Dishary Banerjee1,b) Susmita Bose1,a) 1
W. M. Keck Biomedical Materials Research Laboratory, School of Mechanical and Materials Engineering, Washington State University, Pullman, Washington 99164-2920, USA a) Address all correspondence to this author. e-mail: [email protected] b) This author was an editor of this journal during the review and decision stage. For the JMR policy on review and publication of manuscripts authored by editors, please refer to http://www.mrs.org/editor-manuscripts/. Received: 12 December 2018; accepted: 15 March 2019
The objective of this study was to understand the effects of ceramic polymer composite and pH of the surrounding vicinity on the release kinetics of doxorubicin. Different concentrations of polymers with polycaprolactone (PCL), poly glycolic lactic acid (PLGA), and a blend of PCL–PLGA with hydroxyapatite (HA) were investigated for doxorubicin release at physiological pH of 7.4 and an acidic pH of 5.0 caused by immediate surgery. Burst release of 20% was observed from bare HA at pH 7.4 over a week, whereas all the polymer incorporated discs showed sustained release. The hydrophilic–hydrophobic and hydrophobic– hydrophobic interactions between the polymer and the drug altered by the surrounding pHs were found to be pivotal in controlling the release kinetics of drug. No cytotoxicity of the drug at a concentration of 50 lg per disc was observed at early time points when cultured with osteoblast cells; however, the same drug dosage inhibited osteosarcoma cell viability. This study mainly bases on the comprehension of the effects of chemistry, environment, and polymer–drug interactions, leading to a beneficial understanding towards the design of drug delivery devices.
Introduction Local drug delivery system has been accepted as an alternative to conventional oral dosage to address challenges such as poor targeting and efficacy, severe toxicity in nontarget tissues, and uncontrolled pharmacokinetics [1, 2]. Calcium phosphate (CaP)–based implants, especially HA, have been proven as excellent materials for tissue integration [3, 4, 5, 6] and also as reservoirs for slow drug elution for extended time periods with a variety of surface modifications [7, 8]. Matrix degradation mechanism, drug solubility, polymer–drug interactions, and the surface microstructure have been shown to be pivotal in controlling the drug release kinetics from these CaP-based drug delivery devices [8, 9, 10]. Localized drug delivery still poses an important challenge in the treatment of bone cancer. Much research has been dedicated in the quest of developing technologies for efficient local drug delivery to help in selectively eradicating the
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remnant cancer cells after excision of bone tumor with negligible effects on the healthy bone cells. Although drugs consumed orally are delivered to all body cells by getting absorbed in the blood stream, however, cancer dr
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