03262naa a2200397 a 450000100080000000500110000800800410001902400410006010000230010124501420012426000090026630000120027552020300028765300160231765300270233365300340236065300160239465300170241065300180242765300330244565300250247865300420250365300280254565300320257370000180260570000170262370000200264070000180266070000230267870000180270170000230271970000200274270000180276270000230278077300610280320967602018-10-03       2018    bl uuuu     u00u1 u    #d7 a10.1016/j.eurpolymj.2018.04.0132DOI1 aFERREIRA, L. M. B.  aExploiting supramolecular interactions to produce bevacizumab-loaded nanoparticles for potential mucosal delivery.h[electronic resource]  c2018  a238-250  aMonoclonal antibody (mAb) delivery is gaining importance for local, systemic, and route-specific targeting. Themucus constitutes the main barrier for this type of delivery. In the present study, we aimed to develop a drugdelivery platform by integrating mucus penetrating and mucoadhesive agents into a single system. Our hy-pothesis is that by combining these opposing functions, this system could have its properties modulated ac-cording to specific purposes. Self-assembly studies were conducted ung three classes of building blocks: the protein drug bevacizumab (BVZ), mucus-penetrating polyanion dextran sulfate (DS), mucoadhesive polycations trimethylchitosan (TMC) and chitosan oligosaccharides (COS). We obtained two types of nanoarticles by manipulating supramolecular interactions between the components. Binary protein-polyanion (BVZ/DS) nano-particles showed size of approximately 150 nm and a negative zeta potential. Ternary protein-polyanion-poly-cation (BVZ/DS/COS) nanoparticles were obtained using COS and exhibited 350 nm and a positive zeta potential. Assisted by calorimetric information, we demonstrated that building stable ternary nanoparticles carrying positive charges were not possible using the polycation TMC due to its thermodynamic onstraints. Furthermore, spectroscopy analysis and CAM assay indicated that BVZ continued structurally and functionally stable after its incorporation into the nanoparticles. These two types of nanoparticles exhibited different be-haviors when interacting with mucin, as shown by DLS and AFM studies. While the negatively charged particles promoted dispersion of the mucin network, suggesting a mucus penetrating effect of DS, the positively chargedparticles formed aggregates, probably caused by the mucoadhesive effect of COS. These results highlight the importance of understanding the role of supramolecular interactions, responsible for forming drug delivery systems containing complex molecules, such as proteins and polymers.  aBevacizumab  aDrug delivery platform  aInterações supramoleculares  aMucoadesão  aMucoadhesion  aNanoparticula  aNanopartículas poliméricas  aPenetração do muco  aPlataforma de entrega de medicamentos  aPolymeric nanoparticles  aSupramolecular interactions1 aALONSO, J. D.1 aKIILL, C. P.1 aFERREIRA, N. N.1 aBUZZÁ, H. H.1 aGODOI, D. R. M. de1 aBRITTO, D. de1 aASSIS, O. B. G. de1 aSERAPHIM, T. V.1 aBORGES, J. C.1 aGREMIÃO, M. P. D.  tEuropean Polymer Journalgv. 103, p. 238-250, jun. 2018.