scholarly journals Long-term Stable Cationic Solid Lipid Nanoparticles for the Enhanced Intracellular Delivery of SMAD3 Antisense Oligonucleotides in Activated Murine Macrophages

2012 ◽  
Vol 15 (3) ◽  
pp. 467 ◽  
Author(s):  
Su-Eon Jin ◽  
Chong-Kook Kim

Purpose: Long-term stable cationic solid lipid nanoparticles (cSLNs) were formulated to transfer SMAD3 antisense oligonucleotides (ASOs) into the cells to enhance the intracellular activity of the ASOs. The SMAD3 ASOs were designed to block the inflammatory processes linked to TGFβ/SMAD3 pathway. Methods: The cSLN formulation was prepared by high-pressure homogenization method composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), dioleoylphosphoethanolamine (DOPE), Tween 20, and tricaprin as a solid lipid core (1:1:1:1.67, w/w). The size and the zeta potential of the prepared cSLNs were measured by light scattering. The cSLN/ASO complexes were generated and introduced into the murine macrophage cells. After the treatment of the complexes, the cellular uptake of the complexes was determined by flow cytometry and the intracellular activity of SMAD3 ASOs from the complexes was evaluated by western blotting of SMAD3. In addition, TGFβ1, an upstream molecule of TGFβ/SMAD3 pathway, was monitored by ELISA. Results: The nano-scale sized cSLNs were positively charged and physically stable at 4oC during the storage up to 24 months. The uptake efficiency of the cSLN/ASO complexes into macrophage cells was enhanced up to 80% without cytotoxicity. After the treatment of the cSLN/ASO complexes, SMAD3 as well as TGFβ1 was significantly suppressed based on the SMAD3 ASO activity in the macrophage cells. In addition, the cSLN/ASO complexes prevented the morphological change to dendritic shape in the activated macrophage cells. Conclusion: These results suggest that the cSLNs have a potential to deliver the SMAD3 ASOs to intracellular compartments for the anti-inflammatory effect. The development of this strategy might lead to anti-inflammatory and anti-fibrotic therapies in immunological disorders. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

2020 ◽  
Vol 21 (7) ◽  
Author(s):  
Seyed Sadegh Shahraeini ◽  
Jafar Akbari ◽  
Majid Saeedi ◽  
Katayoun Morteza-Semnani ◽  
Shidrokh Abootorabi ◽  
...  

Abstract In the current research, the main focus was to overcome dermal delivery problems of atorvastatin. To this end, atorvastatin solid lipid nanoparticles (ATR-SLNs) were prepared by ultra-sonication technique. The prepared SLNs had a PDI value of ≤ 0.5, and the particle size of nanoparticles was in the range 71.07 ± 1.72 to 202.07 ± 8.40 nm. It was noticed that, when the concentration of lipid in ATR-SLNs increased, the size of nanoparticles and drug entrapment efficiency were also increased. Results showed that a reduction in the HLB of surfactants used in the preparation of SLN caused an increase in the particle size, zeta potential (better stability), and drug entrapment efficiency. Despite Tween and Span are non-ionic surfactants, SLNs containing these surfactants showed a negative zeta potential, and the absolute zeta potential increased when the concentration of Span 80 was at maximum. DSC thermograms, FTIR spectra, and x-ray diffraction (PXRD) pattern showed good incorporation of ATR in the nanoparticles without any chemical interaction. In vitro skin permeation results showed that SLN containing atorvastatin was capable of enhancing the dermal delivery of atorvastatin where a higher concentration of atorvastatin can be detected in skin layers. This is a hopeful promise which could be developed for clinical studies of the dermal delivery of atorvastatin nanoparticles as an anti-inflammatory agent.


2017 ◽  
Vol 23 (23) ◽  
pp. 4200 ◽  
Author(s):  
Chiara Dianzani ◽  
Federica Foglietta ◽  
Benedetta Ferrara ◽  
Arianna Carolina Rosa ◽  
Elisabetta Muntoni ◽  
...  

2013 ◽  
Vol 14 (2) ◽  
pp. 847-853 ◽  
Author(s):  
Felice Cerreto ◽  
Patrizia Paolicelli ◽  
Stefania Cesa ◽  
Hend M. Abu Amara ◽  
Felicia Diodata D’Auria ◽  
...  

2021 ◽  
Author(s):  
Elham H. Hazfi

The preparation and properties of water-in-oil (W/O) emulsions stabilised solely by adsorbed surface-active solid lipid nanoparticles (SLNs) at the oil-water interface were studied. Monostearin-based SLNs were prepared using food-grade micoremulsions as nanoscle 'reactors'. Hot oil-in-water (O/W) microemulsions (70°C) consisting of monostearin, Tween 20, ethanol and water were crash-cooled to 4°C to promote the liquid-solid transition of the monostearin and thus develop sub-micron solid lipid particles. SLNs obtained from the cooled microemulsions were partially stabilised with addition to lecithin (0.5% w/w) to the microemulsion system. With 2% (w/w) added monstearin, the W/O emulsion was stable for the 14 days of study. The microstructure of the emulsions revealed the presence of two stabilisation mechanisms, namely Pickering-type and continuous phase crystal network stabilisation, which both contributed to slowing dispersed droplet coalescence. Overall, this study demonstrated that surface-active SLNs developed using a microemulsion technique could effectively kinetically stabilise model W/O emulsions.


INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (08) ◽  
pp. 38-48
Author(s):  
S. V Shinde ◽  
S Nikam ◽  
P Raut ◽  
M. K. Ghag ◽  

In the present research work, celecoxib (CXB) loaded solid lipid nanoparticles (SLNs) were prepared using the probe sonication method, wherein Glyceryl monostearate and Tween 80 were used as solid lipid and surfactant, respectively. To obtain the statistically optimized batch, 32 factorial design was applied. The optimized batch was characterized physicochemically and evaluated through DSC, SEM and XRD studies. The mean particle size of the optimized batch was found to be 135.41± 0.24 nm with a mean % entrapment efficiency of 80 ± 1.69%. The optimized batch was further lyophilized and dispersed into 1% w/v Carbopol 934P to form a gel. Prepared gel was further evaluated for in vitro drug release, occlusivity, ex vivo permeability, local toxicity, in vivo anti-inflammatory activity and accelerated stability study. The study resulted in stable, safe and prolonged anti-inflammatory activity with quick onset of action. Hence, celecoxib loaded solid lipid nanoparticles can be considered as promising alternative to conventional topical systems.


2018 ◽  
Vol 164 ◽  
pp. 332-339 ◽  
Author(s):  
Sara Daneshmand ◽  
Mahmoud Reza Jaafari ◽  
Jebrail Movaffagh ◽  
Bizhan Malaekeh-Nikouei ◽  
Mehrdad Iranshahi ◽  
...  

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