Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier

2020 ◽  
Vol 26 (27) ◽  
pp. 3234-3250
Author(s):  
Sushil K. Kashaw ◽  
Prashant Sahu ◽  
Vaibhav Rajoriya ◽  
Pradeep Jana ◽  
Varsha Kashaw ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biomedical Engineering ◽  
Viral Infections ◽  
Slow Release ◽  
Molecular Level ◽  
Release Kinetics ◽  
Biologically Active ◽  
Release Process ◽  
Rapid Release ◽  
Wide Range

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

Two-dimensional analysis of human lymphocyte proteins: I. An assay for lymphocyte effectors.

1981 ◽  
Vol 27 (8) ◽  
pp. 1327-1334 ◽  
Author(s):  
K E Willard ◽  
N G Anderson
Keyword(s):  
Transcriptional Control ◽  
Molecular Level ◽  
Human Lymphocytes ◽  
Biologically Active ◽  
Two Dimensional ◽  
Urinary Proteins ◽  
Active Protein ◽  
Two Dimensional Gel Electrophoresis ◽  
Wide Range ◽  
Normal Human

Abstract We describe an assay for lymphocyte effectors that is capable of establishing the existence of regulators of lymphocyte gene expression (including post-transcriptional control and protein processing) and has the ability to characterize the response at the molecular level. The hypothesis that circulating effectors substances excreted through the kidney can be actively present in human urine was tested with this assay. Thus, biologically active protein molecules in urine were detected at concentrations of less than 1 mg/L and over a wide range of dilutions. Activities were detected and quantitated by culturing human lymphocytes with human urinary proteins in the presence of [35S]methionine and subsequently analyzing the labeled lymphocyte proteins by two-dimensional gel electrophoresis. Thus, protein analysis by two-dimensional gels was used to indirectly detect changes produced in cultured lymphocytes after exposure to regulatory molecules. Proteins or sets of lymphocyte proteins appeared or disappeared after exposure to normal or pathological human urinary proteins. Normal human urinary proteins triggered the appearance of sets of proteins referred to by number as the "Urocon" proteins and suppressed the synthesis of protein sets referred to as "Urocof" proteins. In addition to the normal alterations described, urinary proteins from individuals with influenza or acute leukemia and after renal transplantation were capable of inducing unique alterations in lymphocyte patterns.

scholarly journals Recent advancements in liposome-based strategies for effective drug delivery to the brain

2020 ◽  
Vol 28 ◽  
Author(s):  
Parvin Zaman ◽  
Peter E. Penson ◽  
George E. Barreto ◽  
Amirhossein Sahebkar
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Causes Of Death ◽  
Biologically Active ◽  
Large Molecules ◽  
Wide Range ◽  
Common Causes ◽  
The Central Nervous System ◽  
The Brain ◽  
Active Substances

: Disorders of the central nervous system (CNS) and tumors of the brain are challenging to treat, and they rank amongst the most common causes of death worldwide. The delivery of drugs to the brain is problematic because the blood-brain barrier (BBB) effectively arrests the transport of large molecules (including drugs) from the blood to the CNS. Nanoparticle (NP)-mediated drug delivery has received much interest as a technique to overcome this difficulty. In particular, liposome NPs are promising candidates to carry and deliver drugs across the BBB and into the CNS. Liposomes are easy to prepare, highly biodegradable and biocompatible. Liposomes can be easily modified with various ligands to enable efficient and targeted drug delivery. Liposomes can promote increased cellular uptake of drugs and can reduce the extent to which efflux transporters can remove drugs. Liposomes can be loaded with a wide range of drugs and biologically active substances. In this review, we will summarize recent advances in research relating to liposome-based strategies to enable drug delivery across the BBB.

scholarly journals Modification of Alginates to Modulate Their Physic-Chemical Properties and Obtain Biomaterials with Different Functional Properties

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7264
Author(s):  
Piotr Rosiak ◽  
Ilona Latanska ◽  
Paulina Paul ◽  
Witold Sujka ◽  
Beata Kolesinska
Keyword(s):  
Drug Delivery ◽  
Regenerative Medicine ◽  
Literature Review ◽  
Functional Properties ◽  
Synthetic Peptides ◽  
Chemical Properties ◽  
Biological Properties ◽  
Biologically Active ◽  
Reaction Conditions ◽  
Wide Range

Modified alginates have a wide range of applications, including in the manufacture of dressings and scaffolds used for regenerative medicine, in systems for selective drug delivery, and as hydrogel materials. This literature review discusses the methods used to modify alginates and obtain materials with new or improved functional properties. It discusses the diverse biological and functional activity of alginates. It presents methods of modification that utilize both natural and synthetic peptides, and describes their influence on the biological properties of the alginates. The success of functionalization depends on the reaction conditions being sufficient to guarantee the desired transformations and provide modified alginates with new desirable properties, but mild enough to prevent degradation of the alginates. This review is a literature description of efficient methods of alginate functionalization using biologically active ligands. Particular attention was paid to methods of alginate functionalization with peptides, because the combination of the properties of alginates and peptides leads to the obtaining of conjugates with properties resulting from both components as well as a completely new, different functionality.

scholarly journals A Slow-Release Fertilizer of Urea Prepared via Melt Blending with Degradable Poly(lactic acid): Formulation and Release Mechanisms

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1856
Author(s):  
Mujtahid Kaavessina ◽  
Sperisa Distantina ◽  
Esa Nur Shohih
Keyword(s):  
Molecular Weight ◽  
Lactic Acid ◽  
Slow Release ◽  
Release Kinetics ◽  
Nutrient Balance ◽  
Hydrolytic Degradation ◽  
Poly Lactic Acid ◽  
Release Process ◽  
Slow Release Fertilizer ◽  
Micro Holes

In this research, a low molecular weight poly(lactic acid) (or PLA) synthesized from direct polycondensation was melt compounded with urea to formulate slow-release fertilizer (SRF). We studied the influence of the molecular weight (MW) of PLA as a matrix and the urea composition of SRF towards release kinetics in water at 30 °C. The physical appearance of solid samples, the change in urea concentration, and acidity (pH) of water were monitored periodically during the release test. Three studied empirical models exhibited that diffusion within the matrix dominated the urea release process, especially when the release level was less than 60%. Thus, a lower MW of PLA and a higher urea content of SRF showed a faster release rate. For the entire length of the release experiment, a combination of diffusion and degradation mechanisms exhibited the best agreement with the experimental data. The hydrolytic degradation of PLA may begin after 96 h of immersion (around 60% release level), followed by the appearance of some micro-holes and cracks on the surface of the SRF samples. Generally, this research revealed the good release performance of urea without residues that damage the soil structure and nutrient balance.

scholarly journals Erythrocyte as an ideal carrier for intavascular drug delivery

2020 ◽  
Vol 19 (4) ◽  
pp. 234-242
Author(s):  
L. D. Koleva ◽  
F. I. Ataullakhanov ◽  
E. I. Sinauridze
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Target Organs ◽  
Carrier Erythrocytes ◽  
Wide Range ◽  
Active Substances ◽  
Gradual Release

Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Erythrocytes can act as carriers with the gradual release of a pharmacological agent, as bioreactors with encapsulated enzymes, or as a tool for targeted delivery of drugs to target organs especially tissue macrophages, liver and spleen. To date, red blood cells have been studied as carriers for a wide range of drug compounds, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc. The review is devoted to the advantages of erythrocytes as carriers for the delivery of drugs loaded into the erythrocyte, or related to its surface, and defines the main directions of research on erythrocytes carriers of biologically active substances. Particular attention is paid to in vivo studies that reveal the potential of carrier erythrocytes for clinical use.

Aspergillus sydowii Strain SCAU066 and Aspergillus versicolor Isolate BAB-6580: Potential Source of Xylanolytic, Cellulolytic and Amylolytic Enzymes

2020 ◽  
Vol 14 (2) ◽  
pp. 15
Author(s):  
Zaidah Zainal ariffin
Keyword(s):  
Extracellular Enzymes ◽  
Biologically Active ◽  
Aspergillus Versicolor ◽  
Aspergillus Sydowii ◽  
Aspergillus Tamarii ◽  
Alternative Source ◽  
Amylolytic Enzymes ◽  
Potato Dextrose Broth ◽  
Wide Range ◽  
Pharmaceutical Industries

Fungi is known to produce a wide range of biologically active metabolites and enzymes. Enzymes produced by fungi are utilized in food and pharmaceutical industries because of their rich enzymatic profile. Filamentous fungi are particularly interesting due to their high production of extracellular enzymes which has a large industrial potential. The aim of this study is to isolate potential soil fungi species that are able to produce functional enzymes for industries. Five Aspergillus species were successfully isolated from antibiotic overexposed soil (GPS coordinate of N3.093219 E101.40269) by standard microbiological method. The isolated fungi were identified via morphological observations and molecular tools; polymerase chain reactions, ITS 1 (5’- TCC GTA GGT GAA CCT GCG G3’) forward primer and ITS 4 (5’-TCC TCC GCT TAT TGA TAT GC-3’) reverse primer. The isolated fungi were identified as Aspergillus sydowii strain SCAU066, Aspergillus tamarii isolate TN-7, Aspergillus candidus strain KUFA 0062, Aspergillus versicolor isolate BAB-6580, and Aspergillus protuberus strain KAS 6024. Supernatant obtained via submerged fermentation of the isolated fungi in potato dextrose broth (PDB) and extracted via centrifugation was loaded onto specific media to screen for the production of xylanolytic, cellulolytic and amylolytic enzymes. The present findings indicate that Aspergillus sydowii strain SCAU066 and Aspergillus versicolor isolate BAB-6580 have great potential as an alternative source of xylanolytic, cellulolytic and amylolytic enzymes.

The content of decenoic acids in drone brood preparations and combined preparations based on it

Biomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 389-393
Author(s):  
D.V. Mitrofanov ◽  
N.V. Budnikova
Keyword(s):  
Royal Jelly ◽  
Storage Conditions ◽  
Water Soluble ◽  
Biologically Active Substances ◽  
Biologically Active ◽  
Strict Adherence ◽  
Drone Brood ◽  
Wide Range ◽  
Active Substances ◽  
Melanin Complex

The drone brood contains a large number of substances with antioxidant activity. These substances require stabilization and strict adherence to storage conditions. Among these substances are unique decenoic acids, the content of which is an indicator of the quality of drone brood and products based on it. The ability of drone brood to reduce the manifestations of oxidative stress is shown. There are dietary supplements for food and drugs based on drone brood, which are used for a wide range of diseases. Together with drone brood, chitosan-containing products, propolis, royal jelly can be used. They enrich the composition with their own biologically active substances and affect the preservation of the biologically active substances of the drone brood. Promising are the products containing, in addition to the drone brood, a chitin-chitosan-melanin complex from bees, propolis, royal jelly. The chitin-chitosan-melanin complex in the amount of 5% in the composition of the adsorbent practically does not affect the preservation of decenic acids, while in the amount of 2% and 10% it somewhat worsens. The acid-soluble and water-soluble chitosan of marine crustaceans significantly worsens the preservation of decenoic acids in the product. Drone brood with royal jelly demonstrates a rather high content of decenoic acids. When propolis is introduced into the composition of the product, the content of decenoic acids increases according to the content of propolis.

Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases

2019 ◽  
Vol 26 (23) ◽  
pp. 4323-4354 ◽  
Author(s):  
Ana Cristina Lima Leite ◽  
José Wanderlan Pontes Espíndola ◽  
Marcos Veríssimo de Oliveira Cardoso ◽  
Gevanio Bezerra de Oliveira Filho
Keyword(s):  
Biologically Active ◽  
Neglected Diseases ◽  
Financial Return ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Wide Range ◽  
Methods Of Synthesis ◽  
Current Therapies ◽  
Resistant Strains ◽  
Privileged Structures

Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases. Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field. Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.

An Update on Recent Advances in Cubosome: A Novel Drug Delivery System

2021 ◽  
Vol 21 ◽  
Author(s):  
Madhukar Garg ◽  
Anju Goyal ◽  
Sapna Kumari
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Lipid Bilayers ◽  
Delivery System ◽  
Liquid Crystalline ◽  
Three Dimensional ◽  
Biologically Active ◽  
Potential Applications ◽  
Health Related ◽  
Novel Drug

: Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three dimensional honeycombs like structure provided with two internal aqueous channels for incorporation of number of biologically active ingredients. In contrast liposomes they provide large surface area for incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as method of choice in the sustained release, controlled release and targeted release dosage forms as new drug delivery system for the better release of the drugs. As lot of advancement in the new form of dosage form has bring the novel avenues in drug delivery mechanisms so it was matter of worth to compile the latest updates on the various aspects of mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health related benefits.

Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery

2020 ◽  
Vol 20 ◽  
Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Tilak R. Bhardwaj ◽  
Rajesh K. Singh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Drug Release ◽  
Anticancer Agents ◽  
Release Kinetics ◽  
In Vitro Release ◽  
Specific Treatment ◽  
Drug Conjugates ◽  
Polymer Drug Conjugates

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.

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