Aerosolizable siRNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery

Wang, Jieliang; Hanafy, Mahmoud S.; Xu, Haiyue; Zhai, Yufeng; Ghosh, Debadyuti; Williams, Robert O.; Cui, Zhengrong

doi:10.1016/j.ijpharm.2021.120215

Cited by 82 publications

(61 citation statements)

References 52 publications

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“…These include liposomes, stable nucleic acid lipid particles (SNALPs), solid lipid nanoparticles (SLNs), pH-responsive lipids, and exosomes ( Table 3 and Fig. 6 ) 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 .…”

Section: Sirna Delivery Systems For Treatment Of Ali/ardsmentioning

confidence: 99%

“…Usually, lipids such as fatty acids/esters/alcohols, triglycerides, waxes, and cholesterol, are used in formulating SLNs 128 . Most recently, aerosolizable TNF-α siRNA-encapsulated SLNs were successfully prepared for potential pulmonary delivery, suggesting the possibility to deliver the siRNA-SLNs dry powder into the lung to silence the gene expression of a gene of interest in cells, such as AMs or lung EpiCs 127 .…”

Section: Sirna Delivery Systems For Treatment Of Ali/ardsmentioning

confidence: 99%

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

Zoulikha

Xiao

Boafo

et al. 2022

Acta Pharmaceutica Sinica B

154

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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%

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

154

View full text Add to dashboard Cite

show abstract

“…Finally, due to the ideal aerosol performance properties of the powders prepared by TFFD, the resultant dry powder vaccines are expected to be deliverable through a non-invasive route such as intranasal or pulmonary administration (129,140). In fact, intranasal DelNS1-2019-nCoV-RBD-OPT1, a COVID-19 vaccine candidate based on influenza virus carrying SARS-CoV-2 RBD, has entered phase 1 clinical trial recently (i.e., ChiCTR2000037782) (141).…”

Section: Existing Technologies To Eliminate Requirement Of Cold Tempementioning

confidence: 99%

Next-Generation COVID-19 Vaccines Should Take Efficiency of Distribution into Consideration

2021

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The dire need for safe and effective coronavirus disease (COVID-19) vaccines is met with many vaccine candidates being evaluated in pre-clinical and clinical studies. The COVID-19 vaccine candidates currently in phase 3 or phase 2/3 clinical trials as well as those that recently received emergency use authorization (EUA) from the United States Food and Drug Administration (FDA) and/or other regulatory agencies worldwide require either cold (i.e., 2-8°C) or even freezing temperatures as low as −70°C for storage and distribution. Thus, existing cold chain will struggle to support both the standard national immunization programs and COVID-19 vaccination. The requirement for cold chain is now a major challenge towards worldwide rapid mass vaccination against COVID-19. In this commentary, we stress that thermostabilizing technologies are available to enable cold chain-free vaccine storage and distribution, as well as potential needle-free vaccination. Significant efforts on thermostabilizing technologies must now be applied on next-generation COVID-19 vaccines for more cost-effective worldwide mass vaccination and COVID-19 eradication.

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“…As depicted in Figure 3A, TFF of vaccine formulation containing β-D-mannitol at a concentration of 50 mg/mL resulted in the crystallization of β-D-mannitol mainly in the δ and a polymorphs with the δ polymorph dominating. Our previous work showed also that mannitol crystallizes during TFF in the a polymorph [24] or b and d polymorphs [37]. The distribution of mannitol crystal forms depends on the formulation compostion as well as the freezing and drying conditions [38].…”

Section: Effect Of Stabilizersmentioning

confidence: 99%

“…AddaVax is for research use only. TFFD has been applied to successfully convert biologics, including vaccines, from liquid into stable dry powders [22][23][24][25][26][27]. It was hypothesized that the ultra-rapid freezing, relatively small gas-liquid interface, and low shear stress associated with the thin film freezing (TFF) process would minimize nanoemulsion droplet aggregation or fusion during the freezing step.…”

Section: Introductionmentioning

confidence: 99%

Formulation of Dry Powders of Vaccines Containing MF59 or AddaVax by Thin-Film Freeze-Drying

AboulFotouh

Uno

et al. 2021

Preprint

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Oil-in-water (O/W) nanoemulsion-based vaccine adjuvants such as MF59® are often used in seasonal and pandemic influenza vaccines. However, vaccines containing nanoemulsions require cold chain for storage and are sensitive to accidental freezing. We explored the feasibility of developing dry powders of vaccines adjuvanted with MF59 or AddaVax™, a preclinical grade nanoemulsion that has the same composition and droplet size as MF59, by thin-film freeze-drying (TFFD). AddaVax alone was successfully converted from a liquid to dry powders by TFFD using trehalose as a stabilizing agent while maintaining the droplet size distribution of the AddaVax when reconstituted, whereas subjecting the same AddaVax composition to conventional shelf freeze-drying led to significant aggregation or fusion. TFFD was then applied to convert liquid AddaVax-adjuvanted vaccines containing either model antigens such as ovalbumin and lysozyme, mono-, bi-, and tri-valent recombinant hemagglutinin (rHA) protein-based H1 and/or H3 (universal) influenza vaccine candidates, as well as the MF59-containing Fluad® Quadrivalent influenza vaccine to dry powders. Antigens, stabilizing agents, and buffer showed different effects on the physical properties of the vaccines (e.g., mean particle size and particle size distribution) after subjected to TFFD, but the integrity and hemagglutination activity of the rHA antigens did not significantly change and the immunogenicity of reconstituted influenza vaccine candidates was preserved when evaluated in BALB/c mice. The vaccine dry powder was not sensititve to repeated freezing-and-thawing, in contrast to its liquid counterpart. It is concluded that TFFD can be applied to convert vaccines containing MF59 or an nanoemulsion with the same composition and droplet size as MF59 from liquid to dry powders while maintaining the immunogencity of the vaccines, and it may be used to prepare dry powders of multivalent universal influenza vaccines.

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Aerosolizable siRNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery

Cited by 82 publications

References 52 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

Next-Generation COVID-19 Vaccines Should Take Efficiency of Distribution into Consideration

Formulation of Dry Powders of Vaccines Containing MF59 or AddaVax by Thin-Film Freeze-Drying

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