scholarly journals MS2 Virus-like Particle as an Efficient Drug Delivery Tool: Optimizing the Synthesis and Purification Protocol

2021 ◽  
Author(s):  
Khadijeh Hashemi ◽  
Mohammad Mahdi Ghahramani Seno ◽  
Mohammad Reza Ahmadian ◽  
Bizhan Malaekeh-Nikouei ◽  
Mohammad Reza Bassami ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Precipitation Method ◽  
Rna Sequences ◽  
Bacteriophage Ms2 ◽  
Virus Like Particle ◽  
Effects Of Ph ◽  
Peg Precipitation Method ◽  
The Stability ◽  
Purification Protocol

Abstract Introducing bacteriophage MS2 virus-like particles (VLPs) as gene and drug delivery tools increases the demand for optimizing their production and purification procedure. PEG precipitation method is used efficiently to purify VLPs, while the effects of pH and different electrolytes on the stability, size, and homogeneity of purified MS2 VLPs, and the encapsulated RNA sequences remained to be elucidated.In this regard, a vector, capable of producing VLP with an shRNA packed inside was prepared. The resulting VLPs in different buffers/solutions were assessed for their size, polydispersity index, and ability to protect the enclosed shRNA. We report that among Tris, HEPES, and PBS, with or without NaNO3, and also NaNO3 alone in different pH and ionic concentrations, the 100mM NaNO3-Tris buffer with pH:8 can be used as a new and optimal MS2 VLP production buffer, capable of inhibiting the VLPs aggregation. These VLPs show a size range of 27-30nm and suitable homogeneity with minimum 12-month stability at 4◦C. Moreover, the resulting MS2 VLPs were highly efficient and stable for at least 48 hours in conditions similar to in vivo. These features of MS2 VLPs produced in the newly introduced buffer make them an appropriate candidate for therapeutic agents’ delivery.

scholarly journals Optimizing the synthesis and purification of MS2 virus like particles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Khadijeh Hashemi ◽  
Mohammad Mahdi Ghahramani Seno ◽  
Mohammad Reza Ahmadian ◽  
Bizhan Malaekeh-Nikouei ◽  
Mohammad Reza Bassami ◽  
...  
Keyword(s):  
Size Range ◽  
Therapeutic Agents ◽  
Precipitation Method ◽  
Rna Sequences ◽  
Virus Like Particles ◽  
Bacteriophage Ms2 ◽  
Effects Of Ph ◽  
Peg Precipitation Method ◽  
The Stability

AbstractIntroducing bacteriophage MS2 virus-like particles (VLPs) as gene and drug delivery tools increases the demand for optimizing their production and purification procedure. PEG precipitation method is used efficiently to purify VLPs, while the effects of pH and different electrolytes on the stability, size, and homogeneity of purified MS2 VLPs, and the encapsulated RNA sequences remained to be elucidated. In this regard, a vector, capable of producing VLP with an shRNA packed inside was prepared. The resulting VLPs in different buffers/solutions were assessed for their size, polydispersity index, and ability to protect the enclosed shRNA. We report that among Tris, HEPES, and PBS, with or without NaNO3, and also NaNO3 alone in different pH and ionic concentrations, the 100 mM NaNO3-Tris buffer with pH:8 can be used as a new and optimal MS2 VLP production buffer, capable of inhibiting the VLPs aggregation. These VLPs show a size range of 27-30 nm and suitable homogeneity with minimum 12-month stability at 4 °C. Moreover, the resulting MS2 VLPs were highly efficient and stable for at least 48 h in conditions similar to in vivo. These features of MS2 VLPs produced in the newly introduced buffer make them an appropriate candidate for therapeutic agents’ delivery.

scholarly journals Stability of Engineered Micro or Nanobubbles for Biomedical Applications

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1089
Author(s):  
Beomjin Park ◽  
Semi Yoon ◽  
Yonghyun Choi ◽  
Jaehee Jang ◽  
Soomin Park ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biomedical Applications ◽  
Ultrasonic Field ◽  
Nanometer Scale ◽  
Factors Affecting ◽  
The Core ◽  
Bubble Structure ◽  
The Stability ◽  
The Relationship

A micro/nanobubble (MNB) refers to a bubble structure sized in a micrometer or nanometer scale, in which the core is separated from the external environment and is normally made of gas. Recently, it has been confirmed that MNBs can be widely used in angiography, drug delivery, and treatment. Thus, MNBs are attracting attention as they are capable of constructing a new contrast agent or drug delivery system. Additionally, in order to effectively use an MNB, the method of securing its stability is also being studied. This review highlights the factors affecting the stability of an MNB and the stability of the MNB within the ultrasonic field. It also discusses the relationship between the stability of the bubble and its applicability in vivo.

scholarly journals ISOLATION AND PROPERTIES OF SECRETORY GRANULES FROM RAT ISLETS OF LANGERHANS

1969 ◽  
Vol 41 (1) ◽  
pp. 167-176 ◽  
Author(s):  
S. L. Howell ◽  
D. A. Young ◽  
P. E. Lacy
Keyword(s):  
Islets Of Langerhans ◽  
Secretory Granules ◽  
Sodium Deoxycholate ◽  
Rat Islets ◽  
The Matrix ◽  
Effects Of Ph ◽  
The Stability ◽  
Rat Islets Of Langerhans ◽  
Specific Insulin

A partially purified secretory granule fraction, isolated from rat islets of Langerhans by differential centrifugation, was used for investigating the stability of the beta granules during incubation in various conditions. Effects of pH, temperature, and time were studied; the granules possessed optimal stability at 4° and pH 6.0, and could be solubilized at pH 4.0 or 8.5, or in the presence of sodium deoxycholate, but not by phospholipase c, ouabain, or alloxan. Incubation with glucose or some of its metabolites, or with tolbutamide, ATP, or cyclic 3',5'-AMP did not alter the stability of the beta granules Exogenous insulin-131I was not bound by the isolated granules under the conditions used; no specific insulin-degrading activity could be detected in subcellular fractions of the islets. These findings indicate that intracellular solubilization of the granules with subsequent diffusion of the insulin into the extracellular space is not a likely mode of insulin secretion in vivo, and suggest that a crystalline zinc-insulin complex may exist in the matrix of the beta granules.

Plant Extracts Loaded in Nanostructured Drug Delivery Systems for Treating Parasitic and Antimicrobial Diseases

2019 ◽  
Vol 25 (14) ◽  
pp. 1604-1615 ◽  
Author(s):  
Brenna L.C. Gondim ◽  
João A. Oshiro-Júnior ◽  
Felipe H.A. Fernanandes ◽  
Fernanda P. Nóbrega ◽  
Lúcio R.C. Castellano ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plant Extracts ◽  
Drug Delivery Systems ◽  
Biological Activities ◽  
Delivery Systems ◽  
Active Components ◽  
Current Therapies ◽  
The Stability

Background: Plant extracts loaded in nanostructured drug delivery systems (NDDSs) have been reported as an alternative to current therapies for treating parasitic and antimicrobial diseases. Among their advantages, plant extracts in NDSSs increase the stability of the drugs against environmental factors by promoting protection against oxygen, humidity, and light, among other factors; improve the solubility of hydrophobic compounds; enhance the low absorption of the active components of the extracts (i.e., biopharmaceutical classification II), which results in greater bioavailability; and control the release rate of the substances, which is fundamental to improving the therapeutic effectiveness. In this review, we present the most recent data on NDDSs using plant extracts and report results obtained from studies related to in vitro and in vivo biological activities.

scholarly journals Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 4013
Author(s):  
Liroy Lugasi ◽  
Igor Grinberg ◽  
Rivka Sabag ◽  
Ravit Madar ◽  
Haim Einat ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Self Assembly ◽  
Drug Loading ◽  
Continuous Phase ◽  
Drug Effectiveness ◽  
Long Term Storage ◽  
Behavioral Studies ◽  
Antipsychotic Activity ◽  
The Stability

Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP.

scholarly journals Pectin-Based Nanomaterials: Synthesis, Toxicity and Applications

2021 ◽  
Vol 33 (11) ◽  
pp. 2579-2588
Author(s):  
Mandeep Kaur ◽  
Aditya Wadhwa ◽  
Vineet Kumar
Keyword(s):  
Drug Delivery ◽  
Human Body ◽  
Release Kinetics ◽  
Drug Carrier ◽  
Biological Origin ◽  
Nanomaterials Synthesis ◽  
The Stability ◽  
Kinetics Of

Nanomaterials of biological origin are very useful for drug delivery applications. The stability, biodegradability and biocompatibility of pectin nanomaterials in the human body make them an effective drug carrier. This review focus on different aspect of synthesis, drug encapsulation, drug release and safety of pectin-based nanomaterials. The nanomaterials can be used for the delivery of different hydrophilic and hydrophobic drugs to various organs. The release kinetics of drug loaded pectin-based nanoparticles can be studied in vitro as well as in vivo. The pectin-based nanomaterials have good pharmaco-kinetics and can ensure controlled drug delivery. However, the toxicity of pectin-based nanomaterials to human body needs to be evaluated carefully before industrial scale application.

scholarly journals RNA X-ray footprinting reveals the consequences of an in vivo acquired determinant of viral infectivity

2021 ◽  
Author(s):  
Rebecca Chandler-Bostock ◽  
Richard J Bingham ◽  
Sam Clark ◽  
Andrew J.P. Scott ◽  
Emma Wroblewski ◽  
...  
Keyword(s):  
Protein Subunits ◽  
X Ray ◽  
Bacteriophage Ms2 ◽  
Virus Like Particle ◽  
Lattice Geometry ◽  
Capsid Shell ◽  
Maturation Protein ◽  
Phage Assembly ◽  
Infectious Cycle

The secondary structures of the bacteriophage MS2 ssRNA genome, frozen in defined states, were determined with minimal perturbation using constraints from X-ray synchrotron footprinting (XRF). The footprints of the gRNA in the virion and as transcript are consistent with single, dominant but distinct conformations, and reveal the presence of multiple Packaging Signals potentially involved in assembly regulation that have not been detected by other techniques. XRF also reveals the dramatic effect of the unique Maturation Protein (MP) on both the capsid lattice, and the gRNA conformation inside the phage compared with a virus-like-particle composed only of coat protein subunits. Aspects of genome organisation in the phage, their impacts on the capsid shell, and the distortion of lattice geometry by MP, are hallmarks of molecular frustration. Phage assembly therefore appears to prepare the particle for the next step of the infectious cycle.

Formation and Structure of Casein Micelles in Lactating Mammary Tissue

1970 ◽  
Vol 28 ◽  
pp. 150-151
Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell
Keyword(s):  
Size Distribution ◽  
G Protein ◽  
Milk Proteins ◽  
Mammary Tissue ◽  
Colloidal System ◽  
Casein Micelles ◽  
The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

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