scholarly journals Novel in vitro and in silico tools for the development of mesoporous silica formulations with optimal precipitation inhibitors

2021 ◽  
Author(s):  
◽  
Daniel Joseph Price
Keyword(s):  
Mesoporous Silica ◽  
In Silico ◽  
The Body ◽  
New Method ◽  
Strong Positive Correlation ◽  
Amorphous Form ◽  
Precipitation Inhibition ◽  
Precipitation Inhibitors ◽  
Precipitation Inhibitor ◽  
Polymer Interactions

Formulation scientists have developed a toolkit of strategies that can improve the solubility and subsequent bioavailability of poorly soluble candidates. Amorphous formulations are especially appealing due to the significant improvement in solubility the amorphous form can provide, but must be stabilized for effective performance (Timpe, 2007). 2. The Importance of Drug Polymer Interactions in Precipitation Inhibition Polymeric “precipitation inhibitors” have seen widespread usage in the literature (Warren, 2010). The precipitation inhibition effect of polymers on precipitations is related to interference with nucleation and crystal growth (Xu, 2013). Many techniques have been reported in the literature to predict these interactions, however, they are not suitable to screening due to API and time resources required, which are not amenable to early stage pharmaceutical development. 3. Mesoporous Silica: An Emerging Formulation Technology Mesoporous silicon dioxide has emerged in recent years as a new option for stabilizing the amorphous form. Upon impregnation of the silica with a concentrated drug solution, the drug can be molecularly adsorbed and locally and sterically confined, preventing recrystallization (Ditzinger, 2018). Upon administration of mesoporous silica formulations to the body the amorphous formulation generates supersaturation which must be stabilized using precipitation inhibitors (Guzman, 2007). 4. Co-incorporation: A New Method to Combine Precipitation Inhibitors with Mesoporous Silica There has been no systematic study of how best to incorporate precipitation inhibitors into mesoporous silica formulations. The current standard practice involves combining inhibitors in a physical mixture with the drug-loaded silica, either by pestle and mortar or overhead stirring. Due to the lack of a defined protocol, there is uncertainty about how reliably the precipitation inhibitor is combined with the drug-loaded silica on a batch to batch basis. In this work, a novel co-incorporated formulation of glibenclamide and the precipitation inhibitor, HPMCAS, onto mesoporous silica was described. By co-incorporating the precipitation inhibitor, the formulation significantly outperformed the commonly applied simple physical blend due to the formation of drug-polymer interactions in the solid state. 5. In Silico Pharmaceutics: A New Method to Select Precipitation Inhibitors for Mesoporous Silica An approach that can incorporate understanding of the drug-polymer interactions with a quick and efficient screening process would be very useful. The COnductor like Screening MOdel for Real Solvents (COSMO-RS) is a quantum mechanical theory, which can be used to derive thermodynamic properties of interest. (Klamt, 1993, 1995, 2003). We proposed excess mixing enthalpies of drug and polymer could be calculated using the COSMO-RS theory. This new approach was applied to screen precipitation inhibitors for three model compounds, all of which showed a strong positive correlation between the rank assigned based on the calculated free enthalpy of mixing and the overall formulation performance. 6. Conclusion This body of work aimed to improve the processes underpinning the design and development of mesoporous silica with precipitation inhibitors. Firstly, this involved two extensive literature reviews in the area of solubility enhancement formulation technologies and precipitation inhibition. Secondly, a mechanistic rational and experimental approach was developed to improve the formulation of precipitation inhibitors with mesoporous silica, the “co-incorporation” approach significantly improved process efficiency and formulation performance. Finally, combining insights from the aforementioned review, and learnings from the mechanistic analysis of the “co-incorporation” approach, an in silico screening protocol was developed to calculate the enthalpy of interaction between drug and polymer, to identify the most optimal precipitation inhibitor for a given formulation.

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Nanoscale Drug Delivery Systems for Glaucoma: Experimental and In Silico Advances

2020 ◽  
Vol 20 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Ocular Drug Delivery ◽  
The Body ◽  
Single Wall Carbon Nanotubes ◽  
Blood Retinal Barrier ◽  
Novel Drugs ◽  
Blood Aqueous Barrier

: In this review nanoscale based drug delivery systems particularly in relevance to the antiglaucoma drugs have been discussed. In addition to that, the latest computational/in silico advances in this field are examined in brief. Using nanoscale materials for drug delivery, is an ideal option to target tumours and drug can be released at areas of the body where traditional drugs may fail to act. Nanoparticles, polymeric nanomaterials, single-wall carbon nanotubes (SWCNTs), quantum dots (QDs), liposomes and graphene are the most important nanomaterials used for drug delivery. Ocular drug delivery is one of the most common and difficult tasks faced by pharmaceutical scientists because of many challenges like circumventing the blood–retinal barrier, corneal epithelium and the blood–aqueous barrier. Authors found compelling empirical evidence of scientists relying on in-silico approaches to develop novel drugs and drug delivery systems for treating glaucoma. This review in nanoscale drug delivery systems will help us in understand the existing queries and evidence gaps and will pave way for effective design of novel ocular drug delivery systems

scholarly journals Electrochemotherapy Effectiveness Loss due to Electric Field Indentation between Needle Electrodes: A Numerical Study

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
José Alvim Berkenbrock ◽  
Rafaela Grecco Machado ◽  
Daniela Ota Hisayasu Suzuki
Keyword(s):  
Electric Field ◽  
In Silico ◽  
Treatment Effectiveness ◽  
Numerical Study ◽  
Specific Treatment ◽  
The Body ◽  
Membrane Selectivity ◽  
Chemotherapy Drugs ◽  
Mast Cell Tumor ◽  
Anticancer Treatment

Electrochemotherapy is an anticancer treatment based on applying electric field pulses that reduce cell membrane selectivity, allowing chemotherapy drugs to enter the cells. In parallel to electrochemotherapy clinical tests, in silico experiments have helped scientists and clinicians to understand the electric field distribution through anatomically complex regions of the body. In particular, these in silico experiments allow clinicians to predict problems that may arise in treatment effectiveness. The current work presents a metastatic case of a mast cell tumor in a dog. In this specific treatment planning study, we show that using needle electrodes has a possible pitfall. The macroscopic consequence of the electroporation was assessed through a mathematical model of tissue electrical conductivity. Considering the electrical and geometrical characteristics of the case under study, we modeled an ellipsoidal tumor. Initial simulations were based on the European Standard Operating Procedures for electrochemotherapy suggestions, and then different electrodes’ arrangements were evaluated. To avoid blind spots, multiple applications are usually required for large tumors, demanding electrode repositioning. An effective treatment electroporates all the tumor cells. Partially and slightly overlapping the areas increases the session’s duration but also likely increases the treatment’s effectiveness. It is worth noting that for a single application, the needles should not be placed close to the tumor’s borders because effectiveness is highly likely to be lost.

Locomotory Diseases Influence on Body Equilibrium and Balance

2014 ◽  
Vol 555 ◽  
pp. 652-658 ◽  
Author(s):  
Barbu Cristian Braun ◽  
Ileana Constanta Rosca
Keyword(s):  
Body Mass ◽  
Human Subjects ◽  
Force Plate ◽  
The Body ◽  
The Other ◽  
New Method ◽  
First Person ◽  
Mass Center ◽  
Stability Problems ◽  
Research Stage

The paper describes a new method of body equilibrium evaluation applied for different human subjects, the principal aim being to demonstrate to what extent any locomotory diseases could influence the body stability and equilibrium. The research refers to identify some persons with different locomotory diseases and to find both the influence on equilibrium and stability and if possible to improve them. Our research stage, synthesized in this paper, explains the body equilibrium evaluation in orthostatic posture done for different subjects, aged between 20 and 40 years. A number of 10 relevant persons were considered to be evaluated, 2 of them having some locomotory diseases. The first person presents any neuro-motor stability problems in case of long standing case. The other person has both Achilles tendons torn and operated. All subjects were tested in orthostatic posture, in 3 distinct positions, using a Kistler force plate. The experiments referred to the body mass center (COM) displacement in sagittal and lateral planes, representing an interesting characteristic for its equilibrium. It was shown that the person with diseases affecting stability presented a loss of equilibrium when standing for 10-20 seconds, i.e. higher COM displacements in both planes reported to the other tested subjects.

A Method for Tracking a Solid Body in a Fluid Field in Immersed Boundary Methods

2018 ◽  
Author(s):  
Guangfa Yao
Keyword(s):  
Level Set ◽  
Solid Body ◽  
Volume Fraction ◽  
Transformation Matrix ◽  
The Body ◽  
New Method ◽  
Immersed Boundary ◽  
Body Interaction ◽  
Level Set Function ◽  
Set Function

Immersed boundary method has got increasing attention in modeling fluid-solid body interaction using computational fluid dynamics due to its robustness and simplicity. It usually simulates fluid-solid body interaction by adding a body force in the momentum equation. This eliminates the body conforming mesh generation that frequently requires a very labor-intensive and challenging task. But accurately tracking an arbitrary solid body is required to simulate most real world problems. In this paper, a few methods that are used to track a rigid solid body in a fluid domain are briefly reviewed. A new method is presented to track an arbitrary rigid solid body by solving a transformation matrix and identifying it using a level set function. Knowing level set function, the solid volume fraction can be derived if needed. A three-dimensional example is used to study a few methods used to represent and solve the transformation matrix, and demonstrate the presented new method.

scholarly journals New method for the immobilization of nitroxyl radical on mesoporous silica

2015 ◽  
Vol 203 ◽  
pp. 63-72 ◽  
Author(s):  
A. Machado ◽  
M.H. Casimiro ◽  
L.M. Ferreira ◽  
J.E. Castanheiro ◽  
A.M. Ramos ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Nitroxyl Radical ◽  
New Method

scholarly journals The Short Communication: Polymorphism of myostatin gene and its association with body weight traits in a hybrid of GAMA chicken (Gallus gallus domesticus Linn. 1758)

2019 ◽  
Vol 20 (11) ◽  
Author(s):  
ARDO TANJUNG ◽  
H.T.S.S.G. SARAGIH ◽  
TRIJOKO ◽  
H.P. SOENARWAN ◽  
S. WIDIANTO ◽  
...  
Keyword(s):  
Body Weight ◽  
Pearson Correlation ◽  
Negative Relationship ◽  
Gallus Gallus ◽  
Gallus Domesticus ◽  
The Body ◽  
Strong Positive Correlation ◽  
Gallus Gallus Domesticus ◽  
Myostatin Gene ◽  
Positive Correlation

Abstract. Tanjung A, Saragih HTSSG, Trijoko, Soenarwan HP, Widianto S, Mahardhika IWS, Daryono BS. 2019. Polymorphism of myostatin gene and its association with body weight traits in a hybrid of GAMA chicken (Gallus gallus domesticus Linn. 1758). Biodiversitas 20: 3207-3212. An experiment was conducted to detect SNP of the myostatin gene and its association with the body weight of hybrid chicken crossbreed from F1 Kamper and BC1 Broiler. Four F1 Kamper hens were crossbred with BC1 Broiler rooster. Day old chick (DOC) hatched were maintained for 49 days with body weight measurement every seven days. The blood samples from 49 days old chicken were taken for DNA isolation by Chelex 5% method and then amplification of the myostatin gene. PCR products were sequenced, and sequence alignment was performed using Clustal Omega to obtain SNP. The SNP obtained was analyzed by the Pearson correlation test with the body weight of forty nine-days-old chickens. The body weight of the hybrid chicken is higher than of Pelung chicken but lower than the Broiler. There are 7 SNPs in myostatin gene exons included 2 Adenine insertions, 1 Guanine deletion, and four substitutions (C2244G, G2283A, T4842G, G7378T) that yield nine haplotypes. Six haplotypes had different protein sequences with Myostatin protein, while three haplotypes were identical to Myostatin protein. The correlation analysis showed that there was a strong positive correlation (r = 0.736) between normal Myostatin protein and mutant to chicken body weight at 49-days-old. Adenine insertion to nucleotide 2099-2100 of myostatin gene had a very strong positive correlation (r = 0.800) to 49-days-old chicken body weight, although T4842G substitution had a strong negative relationship (r = -0.773) to 49-days-old chicken body weight. Adenine insertion to nucleotide 2099-2100 of myostatin gene could be a genetic marker of heavier body weight of the hybrid chicken.

scholarly journals Ethanolic Extract of Papaya (Carica papaya) Leaf Exhibits Estrogenic Effects In Vivo and In Silico

2012 ◽  
Vol 3 (2) ◽  
pp. 384
Author(s):  
Raisatun Nisa Sugiyanto ◽  
Rahmi Khamsita ◽  
Marvin Lambertus ◽  
Rohmad Yudi Utomo ◽  
Ratna Asmah Susidarti
Keyword(s):  
Estrogen Receptor ◽  
In Silico ◽  
Carica Papaya ◽  
Ethanolic Extract ◽  
The Body ◽  
Female Rats ◽  
Sprague Dawley ◽  
Docking Score ◽  
Estrogenic Effect

The menopause women have the low level of estrogen in the body. The lack of estrogen changes physiological function in women’s body that affects in health condition. Carica papaya L. leaf contains flavonoid quercetin which exhibits estrogenic effect. The aim of this study is to determine the estrogenic effect of papaya leaves extract (PLE) in vivo, and in silico. Papaya leaves were extracted by ethanol 70% maceration. The in silico study were done by molecular docking between quersetin and Estrogen Receptor (ERα and ERβ) to obtain the docking score. Based on this study, docking score of quercetin was almost similar to the native ligand of ER. The in vivo study was done as follow: 36 female rats Sprague Dawley divided into six groups.  The groups are shame-ovariectomized (S-OVX), control ovariectomized (OVX), CMC-Na control (OVX+CMC-Na), positive control (OVX+Estradiol), and the PLE treatment groups dose 750 mg/kgBW (OVX+750mg/kgBW) and dose 1000 mg/kgBW (OVX+1000 mg/kgBW). Administrations of PLE were done in three weeks orally, while estradiol was administrated intraperitonially. The mammae and uterine were sliced for analysis. Based on the study, the treatment of PLE increased the number of mammae lobules and uterine weight as well as estrogen does.  In summary, PLE can be developed as a source of phytoestrogens.Keywords: Carica papaya L., phytoestrogen, estrogen receptor, mammae lobule, uterine

scholarly journals An in Silico Scientific Basis for LL-37 as a Therapeutic and Vitamin D as Preventive for Covid-19.

2020 ◽  
Author(s):  
Kiran Bharat Lokhande ◽  
Tanushree Banerjee ◽  
K. Venkateswara Swamy ◽  
Manisha Deshpande
Keyword(s):  
Vitamin D ◽  
Receptor Binding ◽  
In Silico ◽  
Large Body ◽  
Inverse Correlation ◽  
Medical Practitioner ◽  
Binding Domain ◽  
The Body ◽  
Receptor Binding Domain ◽  
Vitamin D Levels

<p>Even as clinical trials are underway for vaccines and therapeutics for Covid-19, establishment of modalities with a strong and complete foundation is still awaited and until then, the uncertainty remains associated. Thus, there is a requirement to research as many new and different types of approaches as possible to tackle the pandemic. In this report, <i>in silico</i> scientific findings are presented, which are indicative of the putative potential for the use of the LL-37 human anti-microbial peptide as a therapeutic or possibly even as a prophylactic against SARS-CoV-2. This indication is mainly based on the high structural similarity of LL-37 to the N-terminal helix of the receptor-binding domain of SARS-CoV-2, and the positive prediction of binding of LL-37 to the receptor-binding domain of SARS-CoV-2. Also, as Vitamin D is known to upregulate the expression of LL-37, the vitamin is a candidate preventive molecule. This report also provides the possible basis for why there is an inverse correlation between Vitamin D levels in the body and the severity of or susceptibility to Covid-19, as described in a large body of published literature. The path for development of LL-37 as a therapeutic could be of lesser duration, as LL-37 is native to the human body. With the scientific link put forth in this work, Vitamin D could be used at an effective, medically prescribed dose as a preventive measure. As Vitamin D is insoluble in water, it should be taken only in consultation with a medical practitioner to prevent adverse effects of its accumulation in the body. The information in this report would be valuable in bolstering the worldwide efforts to control the pandemic as early as possible.</p>

Positronium Thermalization Process in Nanoporous Materials and its Influence on the Shape of PALS Spectrum

2008 ◽  
Vol 607 ◽  
pp. 39-41
Author(s):  
Jerzy Kansy ◽  
Radosław Zaleski
Keyword(s):  
Mesoporous Silica ◽  
Pore Size Distribution ◽  
Porous Materials ◽  
Pore Size ◽  
Size Distribution ◽  
Nanoporous Materials ◽  
New Method ◽  
New Model ◽  
Conventional Models ◽  
Mcm 41

A new method of analysis of PALS spectra of porous materials is proposed. The model considers both the thermalization process of positronium inside the pores and the pore size distribution. The new model is fitted to spectra of mesoporous silica MCM-41 and MSF. The resulting parameters are compared with parameters obtained from fitting the “conventional” models, i.e. a sum of exponential components with discrete or/and distributed lifetimes.

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