Functionalized PLGA nanoparticles prepared by nano-emulsion templating interact selectively with proteins involved in the transport through the blood-brain barrier

Autor: Gabriela Calderó, Santiago Grijalvo, A. Dols-Perez, Cristina Fornaguera, María José García-Celma, Conxita Solans, Carmen Quero, Carlos Rodríguez-Abreu, Marta Monge
Přispěvatelé: Fornaguera, Cristina [0000-0002-7014-3213], Quero, Carmen [0000-0003-3599-2778], Calderó, Gabriela [0000-0003-4827-7722], Rodríguez-Abreu, Carlos [0000-0002-5917-6508], Fornaguera, Cristina, Quero, Carmen, Calderó, Gabriela, Rodríguez-Abreu, Carlos
Rok vydání: 2020
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1873-3441
Popis: During the last few decades, extensive efforts has been made to design nanocarriers to transport drugs into the central nervous system (CNS). However, its efficacy is limited due to the presence of the Blood-Brain Barrier (BBB) which greatly reduces drug penetration making Drug Delivery Systems (DDS) necessary. Polymeric nanoparticles (NPs) have been reported to be appropriate for this purpose and in particular, poly(lactic-co-glycolic acid) (PLGA) has been used for its ability to entrap small molecule drugs with great efficiency and the ease with which it functionalizes NPs. Despite the fact that their synthetic identity has been studied in depth, the biological identity of such manufactured polymers still remains unknown as does their biodistribution and in vivo fate. This biological identity is a result of their interaction with blood proteins, the so-called “protein corona” which tends to alter the behavior of polymeric nanoparticles in the body. The aim of the present research is to identify the proteins bounded to polymeric nanoparticles designed to selectively interact with the BBB. For this purpose, four different PLGA NPs were prepared and analyzed: (i) “PLGA@Drug,” in which a model drug was encapsulated in its core; (ii) “8D3-PLGA” NPs where the PLGA surface was functionalized with a monoclonal anti-transferrin receptor antibody (8D3 mAb) in order to specifically target the BBB; (iii) “8D3-PLGA@Drug” in which the PLGA@Drug surface was functionalized using the same antibody described above and (iv) bare PLGA NPs which were used as a control. Once the anticipated protein corona NPs were obtained, proteins decorating both bare and functionalized PLGA NPs were isolated and analyzed. Apart from the indistinct interaction with PLGA NPs with the most abundant serum proteins, specific proteins could also be identified in the case of functionalized PLGA NPs. These findings may provide valuable insight into designing novel vehicles based on PLGA NPs for crossing the BBB.
The authors are grateful to the Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) for funding (Project CTQ2017-84998-P) and the Instituto de Salud Carlos III (ISCIII) (CB06/01/1058). CIBER BBN is an initiative funded by the VI National R+D+I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER actions and financed by ISCIII with assistance from the European Regional Development Fund. The authors want to thank Dr. Miriam Royo’s research group and Dr. Gerardo Acosta for their valuable assistance in HPLC experiments and Ms. Suzanne Córdova for revising and correcting this document. The authors also want to thank NANBIOSIS ICTS and the Nanostructured Liquid Characterization Unit (Unit U12) for DLS measurements. The authors also acknowledge the “Grupo de Nanotecnología Farmacéutica”, from the University of Barcelona (UB), in the Faculty of Pharmacy and Food Sciences, which forms an R&D Associated Unit to CSIC.
Databáze: OpenAIRE
Externí odkaz: