FORMULATION ANDCHARACTERIZATION OF OLANZEPINELOADED MUCOADHESIVE MICROSPHERES

Objective: The objective of this research was to formulate and evaluate olanzapine (OLE) mucoadhesive microsphere prepared using carbopol and sodium combination. OLE having extensive hepatic first pass metabolism and low bioavailability problem, determined the need for the development of sustained release formulation.Methods: OLE mucoadhesive microspheres were prepared by ionic gelation method. OLE mucoadhesive microspheres were prepared by ionic gelation method by using calcium chloride as crosslinking agent. The OLE mucoadhesive microsphere was characterized by particle size measurement, process yield, morphology of microsphere, drug entrapment efficiency, mucoadhesion test, differential scanning calorimetry, powder X-ray diffraction, Fourier transforms infrared (FTIR) study and in-vitro drug release.Results: The OLE mucoadhesive microsphere having mean particle size ranged from 546.0 µm to 554.3 µm, and the entrapment efficiencies ranged from 73% to 96%. All the olanzapine (OLE) microsphere batches showed good in-vitro mucoadhesive property ranging from 75.89% to 96.47% and in the in-vitro wash off test ranging from 68.12% to 81.3%. FTIR studies indicated the no drug-polymer interactions in the ideal formulation F9. Therewere no compatibility issues, and the crystallinity of OLE was found to be reduced shoeing less intense peak in prepared mucoadhesive microspheres, which were confirmed by differential scanning calorimeter and X-ray diffraction studies. Among different formulations, the OLE microspheres of batch F9 had shown the optimum percent drug entrapment of microspheres. Release pattern of OLE from F9 microspheres batch followed Higuchi kinetic model. Stability studies were carried out for F9 formulation at 4°C/ambient, 25±2°C/60±5%, 40±2°C/75±5% relative humidity revealed that the drug entrapment, mucoadhesive behavior, and drug release were within permissible limits.Conclusion: The results obtained in this work demonstrate the use of carbopol and sodium alginate polymer for preparation of mucoadhesive microsphere.Keywords: Ionic gelation method, Gastroretentive delivery, Mucoadhesive microsphere, Carbopol

Antigenic relationship between reactivity to hepatitis B e antigen and 19 kDa protein of Mycobacterium tuberculosis among the Tibetan settlers in Karnataka

McGlynn and her co-workers have reported that among the Vietnamese refugees in Philadelphia and among Alaskan natives who are hepatitis B carriers, there is a statistically significant association between anegative tuberculin test and the presence of hepatitis B e antigen. A repetition of this work among the population of Bangalore did not yield any significant results because of the very low incidence of hepatitis found among this population. However, on the basis of available data that hepatitis B infection is more prevalent among the Mongolian population than among people of other populations, the work was repeated among Tibetans who had settled down in Karnataka. This set of experiments showed that, contrary to the report of McGlynnet al, there is a statistically significant association between apositive tuberculin test and the presence of hepatitis B e antigen and that those individuals who showed the presence of hepatitis B e antigen exhibited less severe form of the disease than those who were negative to this antigen. These findings suggested that immunity to tuberculosis and hepatitis B infections may have a common underlying principle. Data bank search revealed a stretch of amino acid sequences which is common to hepatitis B e antigen and 19 kDa antigen ofMycobacterium tuberculosis. The significance of these results is discussed

Ranking for Database in view of User Opinions

Numerous clients seeking web databases in areas, for example, vehicles, property and so forth has turned into an everyday errand. One of the issues with this assignment is ranking the after effects of a client inquiry. Prior systems for tending to this issue have used to just sort the database values. A consistent idea in the vast majority of these techniques is that ranking is done in a client and inquiry autonomous way. We proposed an inquiry and client subordinate methodology for ranking question results in web databases and it diminishes the quantity of question exchanges. This paper demonstrates to rank the information in database for a specific space in view of the client feelings. The model depends on the likeness client's showcase comparable question or distinctive inquiry ranking over the consequences of comparative inquiries

Homeotic Gene Teashirt (tsh) Has a Neuroprotective Function in Amyloid-Beta 42 Mediated Neurodegeneration

Background: Alzheimer\u27s disease (AD) is a debilitating age related progressive neurodegenerative disorder characterized by the loss of cognition, and eventual death of the affected individual. One of the major causes of AD is the accumulation of Amyloid-beta 42 (Aβ42) polypeptides formed by the improper cleavage of amyloid precursor protein (APP) in the brain. These plaques disrupt normal cellular processes through oxidative stress and aberrant signaling resulting in the loss of synaptic activity and death of the neurons. However, the detailed genetic mechanism(s) responsible for this neurodegeneration still remain elusive. Methodology/Principal Findings: We have generated a transgenic Drosophila eye model where high levels of human Aβ42 is misexpressed in the differentiating photoreceptor neurons of the developing eye, which phenocopy Alzheimer\u27s like neuropathology in the neural retina. We have utilized this model for a gain of function screen using members of various signaling pathways involved in the development of the fly eye to identify downstream targets or modifiers of Aβ42 mediated neurodegeneration. We have identified the homeotic gene teashirt (tsh) as a suppressor of the Aβ42 mediated neurodegenerative phenotype. Targeted misexpression of tsh with Aβ42 in the differentiating retina can significantly rescue neurodegeneration by blocking cell death. We found that Tsh protein is absent/ downregulated in the neural retina at this stage. The structure function analysis revealed that the PLDLS domain of Tsh acts as an inhibitor of the neuroprotective function of tsh in the Drosophila eye model. Lastly, we found that the tsh paralog, tiptop (tio) can also rescue Aβ42 mediated neurodegeneration. Conclusions/Significance: We have identified tsh and tio as new genetic modifiers of Aβ42 mediated neurodegeneration. Our studies demonstrate a novel neuroprotective function of tsh and its paralog tio in Aβ42 mediated neurodegeneration. The neuroprotective function of tsh is independent of its role in retinal determination

3D bioprinting for reconstituting the cancer microenvironment.

The cancer microenvironment is known for its complexity, both in its content as well as its dynamic nature, which is difficult to study using two-dimensional (2D) cell culture models. Several advances in tissue engineering have allowed more physiologically relevant three-dimensional (3D) in vitro cancer models, such as spheroid cultures, biopolymer scaffolds, and cancer-on-a-chip devices. Although these models serve as powerful tools for dissecting the roles of various biochemical and biophysical cues in carcinoma initiation and progression, they lack the ability to control the organization of multiple cell types in a complex dynamic 3D architecture. By virtue of its ability to precisely define perfusable networks and position of various cell types in a high-throughput manner, 3D bioprinting has the potential to more closely recapitulate the cancer microenvironment, relative to current methods. In this review, we discuss the applications of 3D bioprinting in mimicking cancer microenvironment, their use in immunotherapy as prescreening tools, and overview of current bioprinted cancer models