The Stability of lyophilized lipid/DNA complexes during prolonged storage

Molina, Marion d.C.; Armstrong, Taylor; Zhang, Y.e.; Patel, Mayankbhai; Lentz, Yvonne K.; Anchordoquy, Thomas J.

doi:10.1002/jps.20138

Cited by 76 publications

(52 citation statements)

References 58 publications

(91 reference statements)

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“…The ability of charged liposomes to spontaneously complex with negatively charged nucleic acid and antigens greatly simplifies vaccine formulation. Most of the liposome-nucleic acid compounds can also be readily lyophilized, thereby greatly increasing their shelf life and stability (96,97). Future improvements in the design of vaccine adjuvants based on liposome-nucleic acid complexes will require an improved understanding of the effects of size, charge, and liposome composition on interaction with PRRs and induction of specific innate immune responses.…”

Section: Cationic Liposomes-nucleic Acid Complexes As Vaccine Adjuvantsmentioning

confidence: 99%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to markedly potentiate activation of the innate immune system by certain Toll-like receptor (TLR) agonists. The immune enhancing properties of cationic liposomes are most obvious when they are combined with nucleic acid agonists for endosomally-located TLRs, including TLR3, TLR7/8, and TLR9. How this immune potentiation by cationic liposomes is mediated is not completely understood, but is thought to reflect the combined effects of more efficient endosomal targeting, protection from extracellular degradation, and signaling through newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly effective as immunotherapeutics or vaccine adjuvants. As stand-alone immunotherapeutics, liposome-nucleic acid complexes have demonstrated impressive anti-cancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes also show promise for immunotherapy of acute viral and bacterial infections and chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting T cell responses. Thus, cationic liposomes combined with nucleic acids form the basis for a potent and versatile immunotherapeutic platform.

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Section: Cationic Liposomes-nucleic Acid Complexes As Vaccine Adjuvantsmentioning

confidence: 99%

Liposome–nucleic acid immunotherapeutics

Dow¹

2007

Expert Opinion on Drug Delivery

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“…A steady decline in gene transfection efficiency and an increase in lipoplex degradation was observed as the storage temperature of the lipoplexes increased from −20°C to 50°C-60°C. 35,36 For other vectors, such as nanoparticles of calcium phosphate, a slightly greater decrease in transfection efficiency of plasmid DNA is also observed for lyophilized samples stored at 25°C compared with those stored at 4°C. Overall, we suggest that 4°C is the optimal storage temperature for lyophilized reverse transfection formulations.…”

Section: Discussionmentioning

confidence: 98%

Induction of osteogenic differentiation of stem cells via a lyophilized microRNA reverse transfection formulation on a tissue culture plate

Wu¹,

Liu²,

Song³

et al. 2013

IJN

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MicroRNA (miRNA) regulation is a novel approach to manipulating the fate of mesenchymal stem cells, but an easy, safe, and highly efficient method of transfection is required. In this study, we developed an miRNA reverse transfection formulation by lyophilizing Lipofectamine 2000-miRNA lipoplexes on a tissue culture plate. The lipoplexes can be immobilized on a tissue culture plate with an intact pseudospherical structure and lyophilization without any lyoprotectant. In this study, reverse transfection resulted in highly efficient cellular uptake of miRNA and enabled significant manipulation of the intracellular target miRNA level. Reverse transfection formulations containing Lipofectamine 2000 1 µL per well generated much higher transfection efficiency without obvious cytotoxicity compared with conventional and other transfection methods. Further, the transfection efficiency of the reverse transfection formulations did not deteriorate during 90 days of storage at 4°C and −20°C. We then assessed the efficiency of the miRNA reverse transfection formulation in promoting osteogenic differentiation of mesenchymal stem cells. We found that transfection with anti-miR-138 and miR-148b was efficient for enhancing osteogenic differentiation, as indicated by enhanced osteogenesis-related gene expression, amount of alkaline phosphatase present, production of collagen, and matrix mineralization. Overall, the miRNA reverse transfection formulation developed in this study is a promising approach for miRNA transfection which can control stem cell fate and is suitable for loading miRNAs onto various biomaterials.

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“…Otherwise, sugars can crystallize during the drying procedure and the vaccine can be denatured. Three mechanisms have been described to explain the stabilization of biopharmaceuticals such as vaccines by sugars: (a) formation of glassy matrix by sugars which decrease the molecular mobility of the incorporated biopharmaceuticals, 3 (b) formation of hydrogen bonds between sugars and biopharmaceuticals, replacing the hydrogen bonds with water molecules, 4 and (c) formation of a physical barrier by sugars between two molecules, preventing aggregation. 5 In addition to proper drying conditions, other formulation ingredients should also be chosen with care.…”

Section: Dried Vaccines For Needle Free Deliverymentioning

confidence: 99%