title: Bio-inspired materials in drug delivery: Exploring the role of pulmonary surfactant in siRNA inhalation therapy.
abstract: Many pathologies of the respiratory tract are inadequately treated with existing small molecule-based therapies. The emergence of RNA interference (RNAi) enables the post-transcriptional silencing of key molecular disease factors that cannot readily be targeted with conventional small molecule drugs. Pulmonary administration of RNAi effectors, such as small interfering RNA (siRNA), allows direct delivery into the lung tissue, hence reducing systemic exposure. Unfortunately, the clinical translation of RNAi is severely hampered by inefficient delivery of siRNA therapeutics towards the cytoplasm of the target cells. In order to have a better control of the siRNA delivery process, both extra- and intracellular, siRNAs are typically formulated in nanosized delivery vehicles (nanoparticles, NPs). In the lower airways, which are the targeted sites of action for multiple pulmonary disorders, these siRNA-loaded NPs will encounter the pulmonary surfactant (PS) layer, covering the entire alveolar surface. The interaction between the instilled siRNA-loaded NPs and the PS at this nano-bio interface results in the adsorption of PS components onto the surface of the NPs. The formation of this so-called biomolecular corona conceals the original NP surface and will therefore profoundly determine the biological efficacy of the NP. Though this interplay has initially been regarded as a barrier towards efficient siRNA delivery to the respiratory target cell, recent reports have illustrated that the interaction with PS might also be beneficial for local pulmonary siRNA delivery.
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: lynn.debacker@ugent.be.
authors.forename: Lynn
authors.initials: L
authors.lastname: De Backer
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Facultad de Biologia, and Research Institute Hospital 12 Octubre, Universidad Complutense, José Antonio Novais 2, 28040 Madrid, Spain. Electronic address: acerrada@ucm.es.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cerrada
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Facultad de Biologia, and Research Institute Hospital 12 Octubre, Universidad Complutense, José Antonio Novais 2, 28040 Madrid, Spain. Electronic address: jperezgil@bio.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: stefaan.desmedt@ugent.be.
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.affiliation: Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: koen.raemdonck@ugent.be.
authors.forename: Koen
authors.initials: K
authors.lastname: Raemdonck
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D040761:Biomimetic Materials; D032701:Biomimetics / Q000379:methods*; D018014:Gene Transfer Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism*; D053758:Nanoparticles; D036103:Nanotechnology; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods*; D065589:Respiratory Tract Absorption; D012140:Respiratory Tract Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*
chemical_list: D037661:Pulmonary Surfactant-Associated Proteins; D034741:RNA, Small Interfering
keywords: Lung; Nano-bio interface; Nanoparticle; Pulmonary delivery; Pulmonary surfactant; SiRNA