Lyophilization and nebulization of pulmonary surfactant-coated nanogels for siRNA inhalation therapy

Merckx, Pieterjan; Lammens, Joris; Nuytten, Gust; Bogaert, Bram; Guagliardo, Roberta; Maes, Tania; Vervaet, Chris; Beer, Thomas De; Smedt, Stefaan C. De; Raemdonck, Koen

doi:10.1016/j.ejpb.2020.09.011

Cited by 28 publications

(14 citation statements)

References 50 publications

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“…However, the administration of these nanocomposites to the naïve mice increased the inflammatory markers 101 . Most recently, the same group has demonstrated that the proteolipid coated siRNA-loaded nanogels can be freeze-dried and then reconstituted before nebulization for inhalation therapy without influencing their integrity or efficiency 199 .…”

Section: Sirna Delivery Systems For Treatment Of Ali/ardsmentioning

confidence: 99%

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Zoulikha

Xiao

Boafo

et al. 2022

Acta Pharmaceutica Sinica B

139

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The use of small interfering RNAs (siRNAs) has been under investigation for the treatment of several unmet medical needs, including acute lung injury/acute respiratory distress syndrome (ALI/ARDS) wherein siRNA may be implemented to modify the expression of pro-inflammatory cytokines and chemokines at the mRNA level. The clear anatomy, accessibility, and relatively low enzyme activity make the lung a good target for local siRNA therapy. However, the clinical translation of siRNA is hampered by the inefficient delivery of siRNA therapeutics to the target cells due to the properties of naked siRNA. Thus, this review will focus on the various delivery systems that can be used and the different barriers that need to be surmounted for the development of stable inhalable siRNA formulations for human use before siRNA therapeutics for ALI/ARDS become available in the clinic.

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Section: Sirna Delivery Systems For Treatment Of Ali/ardsmentioning

confidence: 99%

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Zoulikha

Xiao

Boafo

et al. 2022

Acta Pharmaceutica Sinica B

139

View full text Add to dashboard Cite

show abstract

“…Indeed, lipo-polymeric NPs (LP NPs) can deliver siRNA targeting the ABCC3 gene to the lungs via dry powder inhalation [ 249 ]. Freeze-dried pulmonary surfactant (Curosurf ® )-coated nanogels could also deliver therapeutic siRNAs to the lungs via a nebulizer [ 250 , 251 ]. Another nanocarrier made of triphenyl phosphonium (TPP)-modified generation 4 poly(amidoamine) (PAMAM) dendrimer (G4NH2-TPP) can be made into inhalation preparations after loading siRNA [ 252 ].…”

Section: Challenges Of Local Delivery Of Np-sirnas—the Importance Of ...mentioning

confidence: 99%

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Zhang

Almazi

Ong

et al. 2022

IJMS

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Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.

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“…Importantly, neither the lyophilization and reconstitution process, nor the subsequent nebulization negatively impacted the physicochemical properties and the biological performance of the particles. Of note, no stabilizing agents such as cryo- and lyoprotectants were required to achieve this feat [ 48 ].…”

Section: Pulmonary Surfactant In the Fight Against Covid-19mentioning

confidence: 99%

“…Unfortunately, current state-of-the-art siRNA nanomedicines have difficulties in overcoming the many extra- and intracellular barriers upon topical administration to the lung, leading to inefficient cytosolic delivery [ 43 , 44 ]. In this regard, it was recently disclosed by Raemdonck and co -workers that exogenous PS has the unexpected property of promoting cytosolic siRNA delivery by polymeric nanomedicines [ [45] , [46] , [47] , [48] , [49] , [50] ]. As such, exogenous PS can be regarded as a multifaceted biomaterial, enabling both direct treatment of COVID-19-related lung dysfunction as well as improved pulmonary delivery of small molecular- and macromolecular drugs.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary surfactant as a versatile biomaterial to fight COVID-19

Herman

Smedt

Raemdonck

2022

Journal of Controlled Release

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Lyophilization and nebulization of pulmonary surfactant-coated nanogels for siRNA inhalation therapy

Cited by 28 publications

References 50 publications

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Pulmonary delivery of siRNA against acute lung injury/acute respiratory distress syndrome

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Pulmonary surfactant as a versatile biomaterial to fight COVID-19

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