Nanomechanical properties of multi-block copolymer microspheres for drug delivery applications

Abstract

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.