Nanoencapsulated budesonide in self-stratified polyurethane-polyurea nanoparticles is highly effective in inducing human tolerogenic dendritic cells

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• 作者：Georgina Fló ; rez-Grau^a ; ¹ ; Pau Rocas^b ; ¹ ; Raquel Cabezó ; n^a ; Carolina Españ ; a^c ; Juliá ; n Pané ; s^a ; ^c ; Josep Rocas^d ; Fernando Albericio^b ; ^e ; ^f ; ^g ; ^{albericio@ub.edu" class="auth_mail" title="E-mail the corresponding author} ; Daniel Bení ; tez-Ribas^h ; ^{daniel.benitez@ciberehd.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APCs ; antigen-presenting cells ; Bayhydur 3100 ; hydrophilic aliphatic polyisocyanate based on hexamethylene diisocyanate (HDI) ; BDS ; budesonide ; DCs ; dendritic cells ; DiI ; 1 ; 1&prime ; -dioctadecyl-3 ; 3 ; 3&prime ; 3&prime ; -tetramethylindocarbocyanine perchlorate+ ; IL- ; interleukin ; MLR ; mixed leucocyte reaction ; PBMCs ; peripheral blood mononuclear cells ; PBLs ; peripheral blood lymphocytes ; PUUa NPs ; polyurethane-polyurea nanoparticles ; PUUa NPs-BDS ; polyurethane-polyurea nanoparticles loaded with Budeso
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：25 September 2016
• 年：2016
• 卷：511
• 期：2
• 页码：785-793
• 全文大小：1419 K

文摘

The design of innovative strategies to selectively target cells, such antigen-presenting cells and dendritic cells, in vivo to induce immune tolerance is gaining interest and relevance for the treatment of immune-mediated diseases.

A novel loaded-nanosystem strategy to generate tolerogenic dendritic cells (tol-DCs) was evaluated. Hence budesonide (BDS) was encapsulated in multiwalled polyurethane-polyurea nanoparticles (PUUa NPs-BDS) based on self-stratified polymers by hydrophobic interactions at the oil-water interface. DCs treated with encapsulated BDS presented a prominent downregulation of costimulatory molecules (CD80, CD83 and MHCII) and upregulation of inhibitory receptors. Moreover, DCs treated with these PUUa NPs-BDS also secreted large amounts of IL-10, a crucial anti-inflammatory cytokine to induce tolerance, and inhibited T lymphocyte activation in a specific manner compared to those cells generated with free BDS. These results demonstrate that PUUa NPs-BDS are a highly specific and efficient system through which to induce DCs with a tolerogenic profile. Given the capacity of PUUa NPs-BDS, this delivery system has a clear advantage for translation to in vivo studies.