Delta-sleep inducing peptide entrapment in the charged macroporous matrices Tatiana V. Sukhanova a, ⁎, Alexander A. Artyukhov b , Yakov M. Gurevich b , Marina A. Semenikhina b , Igor A. Prudchenko c , Mikhail I. Shtilman b , Elena A. Markvicheva d a Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Cell Interactions, Miklukho-Maklaya st., 16/10 Moscow, Russia b Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow, Russia c Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Peptide Chemistry, Miklukho-Maklaya st., 16/10 Moscow, Russia d Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Laboratory Polymers for Biology, Miklukho-Maklaya st., 16/10 Moscow, Russia abstract article info Article history: Received 13 March 2014 Received in revised form 5 May 2014 Accepted 29 May 2014 Available online 6 June 2014 Keywords: Adsorption Biopolymers Drug delivery systems Macroporous polymers Delta-sleep inducing peptide Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protec- tion. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positive- ly charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. © 2014 Elsevier B.V. All rights reserved. 1. Introduction The design of novel biomaterials for tissue engineering and wound healing is one of the important challenges in medicine. As well known, matrices for tissue engineering should provide an optimal microenvironment, in order to support cell adhesion, three-dimension growth, migration and production of extracellular matrix [1,2]. Polymer matrices loaded with various therapeutics can be consid- ered as “depots” for various medicines, for example antibiotics [3] or an- esthetics [4], which can be released in a controlled manner. Various bioactive substances, such as peptides, enzymes, growth factors, DNA, or oligonucleotides used as therapeutic agents are protected by matrix against rapid destruction by peptidases or nucleases [5,6]. In the current study DSIP has been chosen as a model peptide due to its neuroprotective and wound healing properties. Due to its indirect antioxidant activity, DSIP was proposed for burn treatment of experi- mental animals [7]. Moreover, this neuropeptide possesses many other beneficial properties, for example, stress protective, adaptogenic, antiepileptic activities [8–10]. However, DSIP molecule is digested by plasma peptidases in a human body in a few minutes [11]. Thus, DSIP protection against peptidases and prolongation of its lifetime in the body is of great importance. Preparation of hydrogel from polymer frozen aqueous solutions allows designing macroporous systems with developed surface, which provides optimal interaction of polymer surface with entrapped peptide. Various compounds, for example, proteins, peptides etc., can be entrapped into polymer matrices for improvement of their pro- perties [12–14]. These compounds are bound with matrix surface cova- lently or by electrostatic, hydrogen and Van-der-Vaals bonds. Evidently, proteins, peptides and other compounds could be entrapped into these matrices by adsorption due to interaction of oppositely charged functional groups of a compound to be entrapped and a matrix [15]. Since there are two negatively charged s (Asp and Glu) and an N-terminal aromatic amino acid residue (Trp) with amino group as a donor of H + in DSIP structure, we used two oppositely charged porous hydrogels, namely based on 1) dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA); 2) copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) as matrices for DSIP entrapment. Both these polymer materials are widely used for biomedical applications. For example, positively charged poly- DMAEMA and its copolymers are used as restorative and prosthetic materials in tissue engineering, in particular for bone reparation [16, 17] or in stomatology [18,19]. They are also widely employed in drug and gene delivery systems [20–26]. Moreover, poly(DMAEMA) has also antibacterial activity and mucoadhesive properties [24]. Negatively charged poly(AA) shows less mechanical stability and has to be Materials Science and Engineering C 42 (2014) 461–465 ⁎ Corresponding author. E-mail address: sukhanovat@mail.ru (T.V. Sukhanova). http://dx.doi.org/10.1016/j.msec.2014.05.059 0928-4931/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec