DESIGN, FORMULATION AND CHARACTERIZATION OF TENOFOVIR MICROEMULSION AS ORAL DRUG DELIVERY

ABSTRACT The aim of the present research was to design, formulate and evaluate Tenofovir Microemulsion. Tenofovir, a Nucleotide Reverse transcriptase inhibitor belongs to the category of anti retro viral drug. The oral bioavailability of Tenofovir is 25% due to its poor water solubility. An attempt was made to enhance solubility by formulating oral Microemulsion of Tenofovir. The solubility of Tenofovir in various Oils, Surfactants and Cosurfactants were checked to optimize the components of Microemulsion. Pseudo ternary diagrams were constructed to identify the area of Microemulsion region. A Microemulsion system with oleic acid as Oil phase, Tween 20 as surfactant and Ethanol as Cosurfactant was developed for oral delivery of Tenofovir. To achieve the objective of present study, Microemulsion formulations were prepared by using different ratios of Oil, Surfactant: Cosurfactant and Water. The prepared formulations of Tenofovir were characterized for thermo dynamic stability studies, pH, transparency, viscosity, drug content and in vitro drug release. Particle size and Zeta potential of optimized formulation were found to be 54.30nm and -5.61mV. Among four formulations, TME4 shows highest drug release of 86.88%. The invitro release was found to follow Non-fickian diffusion mechanism. These results demonstrate the potential use of Microemulsion for improving the Bioavailability of poor water soluble compound Tenofovir. Key words: Phase diagrams, Centrifugation, Kinetic models, Stability. INTRODUCTION Successful oral delivery of drugs has always remained challenge to the drug delivery field, since approximately 40% of the new drug candidates have poor water solubility associated with low bioavailability. Lipidbased formulations have attracted great deal of attention to improve the oral bioavailability of poorly water soluble drugs. In fact, the most novel approach is to incorporate lipophilic or hydrophilic drugs into inert lipid vehicles such as oils, surfactants through formulating in the form of microemulsions, self-emulsifying formulations. These lead to increased solubilization further increase in therapeutic efficacy. A microemulsion is a system of water, oil and an amphiphile which is a single optically isotropic and thermodynamically stable liquid solution. Microemulsions (μE) are usually in the range of 10-100 nm. These homogeneous systems, which can be prepared over a wide range of surfactant concentration and oil to water ratio, are all fluids of low viscosit

Inheritance of juvenile traits and immune competence in Gramapriya male line chicken

High correlation estimates between body weight and shank length revealed strong association among traits. The significant positive association between 4 and 6 weeks shank length and body weight in the Gramapriya male line chicken suggest the breeder to pre-pone the selection to 4 weeks age which economizes the production cost. Besides, the immune competence of the birds was also found to be better, making them suitable male line for production of backyard poultry varieties

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.Peer reviewe

Learning form Nature to improve the heat generation of iron-oxide nanoparticles for magnetic hyperthermia applications.

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies

Effect of thermal annealing under vacuum on the crystal structure, size, and magnetic properties of ZnFe<SUB>2</SUB>O<SUB>4</SUB> nanoparticles

In this paper, we report the variations in the crystal structure, average particle size, and magnetic properties of ZnFe<SUB>2</SUB>O<SUB>4</SUB> nanoparticles on thermal annealing, using in situ high temperature x-ray diffraction (XRD). Fine powder of ZnFe<SUB>2</SUB>O<SUB>4</SUB> nanoparticles with an average particle size of 9.3 nm, prepared through coprecipitation technique, has been used in these studies. The powder is heated from room temperature to 1000°C, under vacuum in steps of 100°C and the XRD pattern is recorded in situ. A sudden drop in the lattice parameter from 8.478 to 8.468 Å is observed at 800°C, above which it increases with increasing temperature. After annealing at 1000°C, the lattice parameter reduces from 8.441 to 8.399 Å and the magnetization value increases from 5 to 62 emu/g, suggesting the possibility of a conversion of the cubic structured ZnFe<SUB>2</SUB>O<SUB>4</SUB> from normal to inverse spinel structure due to canting of ions between the tetrahedral and octahedral interstitial sites. During annealing, the Zn<SUP>2+</SUP> ions move from tetrahedral site to octahedral site whereas Fe<SUP>3+</SUP> ions redistribute within the octahedral and tetrahedral sites in order to reduce the strain. The increase in the average particle size from 9 to 27 nm, after the thermal annealing at 1000°C, can be attributed to coalescence phenomenon, which starts at 600°C. The estimated value of the activation energy of ZnFe<SUB>2</SUB>O<SUB>4</SUB> nanoparticles during the growth is 18.207 kJ/mol