Mechanical characterization of cross-linked serum albumin microcapsules† Cl ´ ement de Loubens, a Julien Deschamps, * a Marc Georgelin, a Anne Charrier, b Florence Edwards-Levy c and Marc Leonetti * a Controlling the deformation of microcapsules and capsules is essential in numerous biomedical applications. The mechanical properties of the membrane of microcapsules made of cross-linked human serum albumin (HSA) are revealed by two complementary experiments in the linear elastic regime. The first provides the surfacic shear elastic modulus G s by the study of small deformations of a single capsule trapped in an elongational flow: G s varies from 0.002 to 5 N m 1 . The second gives the volumic Young's modulus E of the membrane by shallow and local indentations of the membrane with an AFM probe: E varies from 20 kPa to 1 MPa. The surfacic and volumic elastic moduli increase with the size of the capsule up to three orders of magnitude and with the protein concentration of the membrane. The membrane thickness is evaluated from these two membrane mechanical characteristics and increases with the size and the initial HSA concentration from 2 to 20 mm. 1 Introduction Microencapsulation refers to diverse techniques to enclose active materials within a shell with the aim of protecting them from the outside and to control their spatiotemporal release. This process offers answers to many biotechnological chal- lenges 1–3 such as cancer therapy 4 and cardiovascular treat- ments. 5 Various containers result from encapsulation of a droplet coated with a solid, such as polymeric capsules, or liquid membranes such as vesicles. The membrane may exhibit various mechanical properties that are essential for controlling the delivery of the active materials. 6–8 These characteristics are quite limited for uid vesicles made of lipids: 9 the thickness is xed by the lipid bilayer and their deformation is governed by bending rigidity and membrane incompressibility. 10 While the membrane viscosity is negligible for vesicles, polymersomes are also characterized by shear resistance. 11 The variety of geomet- rical and mechanical properties is widely increased for capsules made of polymers with weak or strong cross-linking. The membrane is supposed to exhibit a viscoelastic behavior and a bending resistance. These characteristics depend on both the chemical composition of the membrane and the preparation process. Understanding the role of the process on the mechanical properties of the membrane is thus of prime importance. Various experiments 12,13 have been developed to test the membrane mechanical properties of capsules. The rst method is dedicated to local stresses applied to the capsule. The prin- ciple is to put a probe in contact with the membrane to study: the compression between two plates, 14 the AFM scanning with a sharp tip 15 or a large colloidal particle 12,16 and the micropipette aspiration. 17 The second method is devoted to global stresses applied to the capsule by means of hydrodynamic ows to study the capsule deformation in a spinning drop apparatus, 18 inside a capillary 19 or in a shear ow. 20,21 Several of these techniques are based on theoretical studies, 22 which are also useful to validate numerical studies. 23–26 In the elastic regime (i.e. under small deformations), the capsule behavior under hydrodynamic stresses has been explored theoretically, 22 giving a relationship between the deformation of the capsule and the surfacic shear modulus. The rst experiments which conrmed these predictions were con- ducted in shear ow 27 based on a cylindrical Couette device and in an elongational ow generated with the so-called four roll mill apparatus. 20 In this paper, we investigated the mechanical behavior of microcapsules that were manufactured by interfacial cross- linking 28,29 of human serum albumin (HSA) with terephthaloyl chloride in a water-in-oil emulsion system. These microcapsules present the advantage of having a biocompatible, biodegrad- able and stable membrane for medical applications. The prep- aration process allowed us to vary easily the HSA concentration. The size distribution of the microcapsules in the different batches was also dependent on the preparation process (Fig. 1). a Aix Marseille Universit´ e, CNRS, Centrale Marseille, IRPHE UMR 7342, 13384 Marseille, France. E-mail: deschamps@irphe.univ-mrs.fr; leonetti@irphe.univ-mrs.fr; Fax: +33 413552001; Tel: +33 413552083 b Aix Marseille Universit´ e, CNRS, CINaM UMR 7325, 13288 Marseille, France c Facult´ e de Pharmacie, Universit´ e de Reims Champagne-Ardenne, CNRS, ICMR UMR 7312, 51687 Reims, France † Electronic supplementary information (ESI) available: Fig. S1 of the load and unload of the AFM probe during one indentation. See DOI: 10.1039/c4sm00349g Cite this: Soft Matter, 2014, 10, 4561 Received 13th February 2014 Accepted 3rd April 2014 DOI: 10.1039/c4sm00349g www.rsc.org/softmatter This journal is © The Royal Society of Chemistry 2014 Soft Matter, 2014, 10, 4561–4568 | 4561 Soft Matter PAPER Published on 12 May 2014. Downloaded by Bibliotheque Interuniversitaire DAix Marseille on 12/06/2014 07:43:27. View Article Online View Journal | View Issue