Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization

Ball, Rebecca L.; Bajaj, Palak; Whitehead, Kathryn A.

doi:10.2147/ijn.s123062

Cited by 192 publications

(205 citation statements)

References 39 publications

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“…1 ) demonstrated that LNPs maintained stability and gene silencing efficacy in HeLa cells following exposure to a wide range of buffer pHs (1–9). Similar results had been found previously for long term LNP storage in solutions of different pH 46 . These data suggest that pH instability in the GI tract will not adversely affect lipid nanoparticle mediated gene silencing.…”

Section: Discussionsupporting

confidence: 91%

Oral delivery of siRNA lipid nanoparticles: Fate in the GI tract

Ball

Bajaj

Whitehead

2018

Sci Rep

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Oral delivery, a patient-friendly means of drug delivery, is preferred for local administration of intestinal therapeutics. Lipidoid nanoparticles, which have been previously shown to deliver siRNA to intestinal epithelial cells, have potential to treat intestinal disease. It is unknown, however, whether the oral delivery of these particles is possible. To better understand the fate of lipid nanoparticles in the gastrointestinal (GI) tract, we studied delivery under deconstructed stomach and intestinal conditions in vitro. Lipid nanoparticles remained potent and stable following exposure to solutions with pH values as low as 1.2. Efficacy decreased following exposure to “fed”, but not “fasting” concentrations of pepsin and bile salts. The presence of mucin on Caco-2 cells also reduced potency, although this effect was mitigated slightly by increasing the percentage of PEG in the lipid nanoparticle. Mouse biodistribution studies indicated that siRNA-loaded nanoparticles were retained in the GI tract for at least 8 hours. Although gene silencing was not initially observed following oral LNP delivery, confocal microscopy confirmed that nanoparticles entered the epithelial cells of the mouse small intestine and colon. Together, these data suggest that orally-delivered LNPs should be protected in the stomach and upper intestine to promote siRNA delivery to intestinal epithelial cells.

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Section: Discussionsupporting

confidence: 91%

Oral delivery of siRNA lipid nanoparticles: Fate in the GI tract

Ball

Bajaj

Whitehead

2018

Sci Rep

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“…NP morphology and size distribution may also be key factors for innovative oral care applications, as they are described as strategical parameters in other application fields dealing with nanometer-size particles [15][16][17][18]. Indeed, the expected nanometer-size effect on NP properties is generally claimed to be more efficient, since the size distribution is narrow, and the shape is homogeneous.…”

Section: Properties and Structural Features Of Nanosystems (Nanomatermentioning

confidence: 99%

Nanoparticles as Anti-Microbial, Anti-Inflammatory, and Remineralizing Agents in Oral Care Cosmetics: A Review of the Current Situation

et al. 2020

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Many investigations have pointed out widespread use of medical nanosystems in various domains of dentistry such as prevention, prognosis, care, tissue regeneration, and restoration. The progress of oral medicine nanosystems for individual prophylaxis is significant for ensuring bacterial symbiosis and high-quality oral health. Nanomaterials in oral cosmetics are used in toothpaste and other mouthwash to improve oral healthcare performance. These processes cover nanoparticles and nanoparticle-based materials, especially domains of application related to biofilm management in cariology and periodontology. Likewise, nanoparticles have been integrated in diverse cosmetic produces for the care of enamel remineralization and dental hypersensitivity. This review summarizes the indications and applications of several widely employed nanoparticles in oral cosmetics, and describes the potential clinical implementation of nanoparticles as anti-microbial, anti-inflammatory, and remineralizing agents in the prevention of dental caries, hypersensitivity, and periodontitis.

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“…The preservation of the physical integrity of liposomes during freeze-drying process it is the primordial importance and can be achieved by the inclusion of saccharides at the final formulations. Since the stabilization effect promoted by cryo/lyoprotectants is concentration-dependent (Ball et al, 2017), we compared the protective effect of five saccharides at different concentrations on the final formulation. The fusion or aggregation of liposomes during the freeze-drying process was monitored by measuring the size distribution of liposomes after freeze-drying-rehydration cycle and compared with the results of freshly prepared liposomes.…”

Section: Influence Of Saccharides On Liposomes' Size Distributionmentioning

confidence: 99%

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

Guimarães

Noro

Silva

et al. 2019

Front. Bioeng. Biotechnol.

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The production of freeze-dried liposomes encapsulating drugs is considered a key challenge since the drugs are prone to leakage. The aim of this work was to study the effect of different saccharides on preserving the stability and drug retention capacity of a previously developed liposomal formulation, when subjected to a freeze-drying process. The protective role of trehalose, lactose, glucose, mannitol and sucrose, known for their cryo/lyoprotective effect, was tested by addition of different concentrations to liposomes. Sucrose, in a concentration dependent manner (8:1 sugar:lipids mass ratio) proved to be a suitable cryo/lyoprotectant of these liposomes. Effectively, this saccharide prevents the fusion or/and aggregation of the liposomal formulation, protecting the integrity of the freeze-dried empty liposomes. The liposomal formulation containing sucrose was studied in terms of morphology, concentration, and anticancer drugs retention ability. The study involved two drugs encapsulated in the aqueous core, methotrexate (MTX) and doxorubicin (DOX), and one drug located in the lipid bilayer, tamoxifen (TAM). After the freeze-drying process, liposomes with sucrose encapsulating drugs revealed high physical stability, maintaining their narrow and monodisperse character, however high leakage of the drugs encapsulated in the aqueous core was observed. Otherwise, no significant drug leakage was detected on liposomes containing the TAM, which maintained its biological activity after the freeze-drying process. These findings reveal that sucrose is a good candidate for the cryo/lyoprotection of liposomes with drugs located in the lipid bilayer.

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Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization

Cited by 192 publications

References 39 publications

Oral delivery of siRNA lipid nanoparticles: Fate in the GI tract

Oral delivery of siRNA lipid nanoparticles: Fate in the GI tract

Nanoparticles as Anti-Microbial, Anti-Inflammatory, and Remineralizing Agents in Oral Care Cosmetics: A Review of the Current Situation

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs

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