Nanomechanical properties of multi-block copolymer microspheres for drug delivery applications.
Biodegradable polymeric microspheres are interesting drug delivery vehicles for site-specific sustained release of drugs used in treatment of osteoarthritis. We study the nano-mechanical properties of microspheres composed of hydrophilic multi-block copolymers, because the release profile of the microspheres may be dependent on the mechanical interactions between the host tissues and the microspheres that aim to incorporate between the cartilage surfaces. Three different sizes of monodisperse microspheres, namely 5, 15, and 30μm, were tested in both dry and hydrated (swollen) states. Atomic force microscopy was used for measuring nanoindentation-based force-displacement curves that were later used for calculating the Young׳s moduli using the Hertz׳s contact theory. For every microsphere size and condition, the measurements were repeated 400-500 times at different surface locations and the histograms of the Young׳s modulus were plotted. The mean Young׳s modulus of 5, 15, and 30μm microspheres were respectively 56.1±71.1 (mean±SD), 94.6±103.4, and 57.6±58.6MPa under dry conditions and 226.4±54.2, 334.5±128.7, and 342.5±136.8kPa in the swollen state. The histograms were not represented well by the average Young׳s modulus and showed three distinct peaks in the dry state and one distinct peak in the swollen state. The peaks under dry conditions are associated with the different parts of the co-polymeric material at the nano-scale. The measured mechanical properties of swollen microspheres are within the range of the nano-scale properties of cartilage, which could favor integration of the microspheres with the host tissue.
Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands; Department of Orthopaedics and Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands.
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PR
Moshtagh
Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands.
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J
Rauker
Department of Orthopaedics, Erasmus Medical Centre, Rotterdam, The Netherlands.
M J
MJ
Sandker
Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands.
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MR
Zuiddam
Kavli Institute of Nanoscience, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands.
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FW
Dirne
InnoCorePharmaceuticals, L.J. Zielstraweg 1, Groningen 9713GX, The Netherlands.
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E
Klijnstra
InnoCorePharmaceuticals, L.J. Zielstraweg 1, Groningen 9713GX, The Netherlands.
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L
Duque
InnoCorePharmaceuticals, L.J. Zielstraweg 1, Groningen 9713GX, The Netherlands.
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R
Steendam
Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands; Department of Orthopaedics and Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands.
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H
Weinans
Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, Delft 2628 CD, The Netherlands. Electronic address: a.a.zadpoor@tudelft.nl.
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Zadpoor
D004337:Drug Carriers / Q000737:chemistry*; D055119:Elastic Modulus; D008422:Materials Testing; D055595:Mechanical Phenomena; D008863:Microspheres; D036103:Nanotechnology; D011108:Polymers / Q000737:chemistry*
D004337:Drug Carriers; D011108:Polymers
Controlled release; Hydrophilic multi-block copolymer; Mechanical properties; Monodisperse microspheres; Nanoindentation