Pharmacogenetics is the study of genetic basis in the individual response to drugs. A thorough knowledge of this will lead to a future where tailor-made drugs, suiting an individual, can be used. Scandinavian countries have been known for wide usage of pharmacogenetics and the most widely used application is for genotyping CYP2D6 in treating psychiatric illness. The CYP-450 enzyme, a super family of microsomal drug-metabolizing enzymes, is the most important of enzymes that catalyzes phase-I drug metabolism reaction. CYP2D6 is a member of this family and it has been most intensively studied and the best example of pharmacogenetics variation in drug metabolism. Neuro-transmitter and drug acting CNS viz. codeine, dextromethorphan, metoprolol and tryptyline etc. are well metabolized by this enzyme. Thus, CYP2D6 is one of the most important and responsible enzymes which regulates bioavailability and metabolism of drug. Presently 75 alleles of CYP2D6 have been described which are responsible for variance of metabolism and toxicity of drugs. Thus, by determining variance of CYP2D6 using molecular approaches viz., PCR, real-time PCR, DNA micro-array and molecular docking can determine the adverse effects, drug toxicity, bioavailability and therapeutic potential of new drug.
The EGFR family of Receptor Tyrosine Kinases (RTKs) consists of 4 members (collectively referred to as the ErbB or HER family): EGFR itself, ErbB2 (HER2/Neu), ErbB3 (HER3) and ErbB4 (HER4). Like all RTKs, each ErbB receptor comprises a large extracellular region, a single spanning trans-membrane (TM) domain, an intracellular ABSTRACT EGFR is a tyrosine kinase receptor that has a role in the tumorigenesis of many types of solid tumors. Aberrantly phosphorylated or overexpressed EGFR is associated with cellular proliferation, prevention of apoptosis, activation of invasion and metastasis, and stimulation of tumor-induced neovascularization. EGFR's hyperactivity has been observed in ovarian cancer. Although conventional chemotherapy and surgery for advanced ovarian cancer have improved over the years, still there is a critical need for the development of molecular targeted therapies. The major challenge for this approach is the complete understanding of the protein structure of this mega receptor. In this study, we explored this receptor using in silico tools. The protein structure of the EGFR kinase domain (PDB ID: 1M17) and co-crystal containing EGFR and PTP1B kinase domain fragment (PDB ID: 3I7Z) were obtained from the RCSB Protein Data Bank. We performed protein-protein docking using BioLuminate. It was found in this study that the DADEYL segment of EGFR (position 988-993) which includes autophosphorylated tyrosine at position 992, is the segment that is responsible for the overexpression of this receptor in ovarian cancer. There are currently two main classes of clinically-approved drugs which downregulate EGFR activity; tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (Mabs). However, treatment with both type of therapies has been met with shortcomings. Therefore, there is a need for further studies to explore the suitable ligands that can downregulate its activity.
Diclofenac sodium were taken as a model drug and belongs to NSAIDS. Diclofenac sodium prevents production of prostaglandins and thus exerts its analgesic action and inhibits leukocyte formation to induce anti-inflammatory action. It is tremendously recommended to reduce and overcome signs and symptoms of rheumatoid arthritis, osteo-arthritis andankylosing spondylitis. This present study was to investigate the dissolution profile and release kinetics of modified release diclofenac sodium microspheres containing sodium alginate and Eudragit S-100. Microspheres were prepared by using ionotropic gelation technique and coated by using coacervation phase separation method using different ratios of eudragit S100 which is a pH sensitive polymer. Both coated and uncoated diclofenac sodium microspheres were evaluated for % yield, entrapment efficiency, flow property, in vitro percent drug release. which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 450 to 550 μm and the size of the coated microspheres ranged from 500 to 700 μm. The core microspheres sustained the release for 12hrs in a pH progression medium mimicking the condition of GIT. The release studies of coated microspheres were performed in a similar dissolution medium as mentioned above. In acidic medium, the release rate was much slower. However, the drug was released quickly at pH 7.4 and their release was sustained up to 24 hrs. Finally, it was concluded that eudragit L100 and ethyl cellulose were appropriate polymers to prepare microspheres of diclofenac sodium as modified release drug delivery system.
Improvement in the solubility of a hydrophobic drug has a significant role in formulation development. The target of this study was the use of solid dispersion and inclusion complex method to enhance and to compare the watery solubility and dissolution qualities of Rifabutin. Various strategies in various proportions have been used in the preparation of the consideration complex with ß-cyclodextrin (ß-CD) and Hydroxypropyl-ß-cyclodextrin (HPß-CD) and found that the better-improved solubility has been seen in kneading technique (AK1) in comparison to the physical mixture method and solvent evaporation method. Various techniques were applied in the preparation of the solid dispersion of Mannitol and polyethene glycol (PEG) 4000. They observed that solvent evaporation (CS4) had shown the better improvement of solubility when compared with the physical mixture method and kneading method. As the two methodologies were analysed, it was observed that the inclusion complex technique was far better as it caused a noteworthy enhancement in dissolution profile (99.23±0.25). The drug content was calculated (99.15±0.14) and % inclusion yield was calculated (99.5 %), which was found to be maximum with the kneading technique (AK1). The characterization FTIR and SEM of the complexes shows that the drug had an amorphous structure. The amorphous structure of a drug has higher dissolution potential than the crystalline structure of the drug. The IR Spectroscopy and Scanning electron microscopy (SEM) were done to check their impact on dissolution behaviour and any if there was any physicochemical interaction between the carrier and the drug.
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