Thursday 26 April 2018

Bioconjugated Nanogels


Nanogels are otherwise called as nanocarriers for the encapsulation and delivery of biomolecules. Designing nanogels as delivery systems for biomolecules with a capacity to respond to the external physical and chemical signals like pH and temperature. Moreover, it has enhanced permeability and retention (EPR) effect, due to their extremely small size. There are many advances that have been developed in designing nanogels for various purposes. Some of them are as follows:

  • Nanogels for intracellular delivery of genetic materialNowadays, gene therapy designed for delivery of antisense oligodeoxynucleotides (ODNs), plasmid DNA (pDNA), siRNAs and micro RNAs (miRNAs) used in targeted inhibition of specific mRNA sequences has developed as one of the most favourable method to treat and diagnose diseases like cancer, neurodegenerative disorders and viral infections. However, the major tests in designing an intracellular gene delivery system exist in crossing the cell membranes without being premature degraded by endogenous enzymes and providing a controlled release of the genetic material into the cell nucleus without inducing cytotoxicity and an immune response following degradation.
  • Nanogels for specific targeted protein delivery - The major problem in using proteins and peptides as therapeutic agents are the protein stabilization in delivery reservoirs at physiological pH values and temperatures and the proper design of protein carriers for the sustained and targeted delivery. One of the approaches in overcoming these limitations is to entrap proteins into hydrogel nanoparticles (nanogel), which can reduce denaturation of proteins by forming a colloidal stable complex with proteins at the nanometer scale (<50 nm).
  • Bioconjugated hydrogel nanoparticle as vaccine delivery or adjuvant systemsRecently, multi-responsive polymeric nanogels have developed a new vaccine delivery system which is capable of initiating innate immune response or enhancing antigen delivery. Therefore, in the case of genetic material and protein encapsulation, nanogels intrinsic properties allow protecting vaccine antigens from degradation in vivo and, by bioconjugation with antibodies or specific ligands, could increase active targeting specificity. Among them, polysaccharide-based nanogels such as cationic cholesterol-bearing pullulan (cCHP) appear to be very appealing as vaccine delivery systems due to their great biocompatibility and the abundance in unprocessed sources.

Limitation of using nanogels as targeted delivery systems is represented by their low target site specificity. Therefore, by conjugation of nanogels or nanogel compounds with biomolecules such as ligands, proteins or other molecules having molecular recognition specificity, the specificity for targeted delivery will improve. Attachment of biomolecules allows a rapid internalization of nanogels into the cells through endocytosis.

Thursday 12 April 2018

Stem Cells for Neurological disorders



Due to the loss of neurons and glial cells, neurological disorders like Parkinson’s disease, stroke and multiple sclerosis are caused. Nowadays, stem cells are cultured to develop neurons and glia to minimise the neurological disorders.  Moreover, efforts have been taken to reduce the death of neurons and glial cells produced by stem cells, within the central nervous system.

On account of a few disorders, increases can probably be induced just with transplanted cells produced from undifferentiated cells in vitro, while in different conditions the stimulation of endogenous CNS stem cells might be valuable. In the case of Huntington’s disease, it is caused by the demise of projection neurons in the striatum. Stem cell treatment means to re-establish or save brain function by replacing and ensuring striatal neurons. In creature models of HD, cell substitution utilizing fetal striatal neurons advances functional recovery and some proof from clinical trials shows this can also happen in patients. By contrast, stem cell based methodologies are still in their earliest stages, and the reproduction of striatal neural hardware has not been appeared in animals.

Before we apply stem-cell treatments to patients, we should have the capacity to control the expansion and separation of stem cells into particular cell phenotypes and to prevent tumor formation. Besides, the viability of stem cells and their systems of activity ought to be exhibited in animal models with pathology and symptomatology resembling the human sickness. It might be hard to interpret information got in creatures to people as a result of animal varieties contrasts in the level of neuronal plasticity and an inadequate learning of illness mechanisms. We should see how to impact the neurotic tissue condition, including inflammatory and resistant responses, to permit productive repair. Finally, we should recollect that however energizing the neurobiological components may be, the clinical convenience of stem cells will be controlled by their capacity to provide patients with neurological disorders with protected, durable and considerable upgrades in quality of life.


Friday 6 April 2018

The Druggable Genome


                                 
The subsets of approximately 30,000 genes in the human genome that can bind to drug like molecules by expressing proteins are called as “The Druggable Genome”.  This concept is raised because of the limitation of molecular targets for which commercially viable compounds can be developed. This means that “The Druggable Genome” which has the ability to produce proteins to bind with drugs.
Commercially viable drug means an orally bioavailable compound. Physico-chemical properties are necessary to improve the oral bioavailability of drug which can be formalized by the Lipinski “rule of five” analysis. Most successful drug achieves their activity by searching for a binding site on protein with a small endogenous molecule. It is necessary that a drug must bind to its target molecule with a reasonable potency, to be more effective.
Survey has been taken to find the molecular targets for a drug to bind on its binding site. Analysis of International Drug Database and the Pharmaprojects Database recognise 399 non-redundant molecular targets. In that, several proteins are targeted by experimental drugs and some are eliminated because of its inactivity according to the rule of five analysis. Most of the drugs identified in this survey are competitive. Those targets fall into the six gene families:
·         G-protein Coupled Receptors (GPCRs)
·         Serine/Threonine and Tyrosine protein kinases
·         Zinc metallo-peptidases
·         Serine proteases
·         Nuclear hormone receptors
·         Phosphodiesterases
New methods such as protein drugs, antibody therapies, DNA vaccines and non-oral drug delivery systems, could expand the range of potential targets those which can’t be identified by rule of five analyses. The limited number of molecular targets for the drug suggest that the druggable genome to be produced in a cost-effective manner. This will be the major innovation for the pharmaceutical industry, not just in the case of science, but also in the case of business.


Chemotherapy

Chemotherapy  is a type of  cancer treatment  that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. Ch...