Delivery Methods for Treatment of Tuberculosis

Delivery Methods for Treatment of Tuberculosis INTRODUCTION The Mycobacterium tuberculosis is a rod-shaped bacillus bacterium which is responsible for an infectious disease tuberculosis. Tuberculosis is chronic bacterial, air borne, contagious disease, which commonly affects lungs and spreads from person to person when active TB patient expels bacteria by coughing or sneezing.(Villemagne et al., 2012). After HIV, Tuberculosis claims world’s second deadliest disease caused by single infectious agent.(Moualeu et al., 2015). In worlds population, one third of individuals are infected with dormant infection, but only 10% of infected people will be symptomatic.(Villemagne et al., 2012). As mentioned in WHO data, yearly global tuberculosis report 2014, it is estimated that 9 million people were symptomatic and develop active TB and out of them, 1.5 million people were died in 2013. Probability of occurrence of TB in HIV patients is high because 360000 out of the 1.5 million deaths were HIV positive. Most of TB cases occur in poorest countrie s like South-East Asia and West Pacific and African regions. It also affects countries like India and China to some extent. Tuberculosis is a preventable and curable disease with effective diagnosis and treatment because 37 million lives were saved between 2000 and 2013.(WHO,2014). The effective treatment of tuberculosis follows multi drug regimens, in which first-line therapy includes four drugs (isoniazid, rifampicin, ethambutol, pyrazinamide) administered during initial intensive stage for two months and followed by continuous phase with rifampicin and isoniazid for four months.(Sosnik et al., 2010). When first-line drugs are mismanaged, therapeutic failure occurs, which leads to multi-drug resistant TB (MDR-TB) which is difficult to treat. Then second line agents such as flouroquinolones and aminoglycosides are given, which are more expensive, more toxicity and less potent. Next stage follows extensively drug resistant TB(XDR-TB) which occurs when second line agents are misused, and disease becomes severe.(Kaur and Singh, 2014). Rifampicin is one of the potent and effective antibiotic and is first drug of choice for long term continuous therapy (six months) and it is having severe side effects as acute renal failure, hepatotoxicity.(Son and McConville, 2011). Chemical name of rifampicin is 3-[[(4-methyl-1-piperazynl)imino]-methyl]-rifamycin.(Argekar et al., 1996). It shows bactericidal activity by binding to ÃŽ ²-subunit of the DNA dependent RNA polymerase and inhibits the bacterial RNA synthesis. Rifampicin facing severe toxicity problems can be solved by reducing the frequency of administration and maintaining a controlled release which is possible by lipid based nanoparticles.(Labuschagne et al., 2014). It is classified as BCS class Ó Ãƒâ€œÃ‚  drug (low solubility and high permeability) and due to poor aqueous solubility and poor bioavailability, this drug is best suitable for lipid based nanocarriers which shows good lipid solubility.(Moretton et al., 2010). Cubosomes are lipid based sub-micron, discrete nanoparticles of liquid crystalline phase with cubic crystallographic symmetry.(Achouri et al., 2014). When amphiphilic lipid is made contact with excess water then it forms a self-assembled liquid crystalline structure of bicontinuous cubic phase and inverse hexagonal phases.(Nguyen et al., 2011). Cubosomes are composed of a lipid and surfactant, first lipid (monoolein) due to its amphiphilic nature it has an ability to solubilize both hydrophilic, hydrophobic and amphiphilic molecules. It is non-toxic, biodegradable and biocompatible material, which is approved by FDA inactive ingredients. Second hydrophilic non-ionic surfactant (poloxamer 407), it is triblock copolymer two hydrophilic blocks of polyethylene oxide (PEO) and hydrophobic block of polypropylene oxide (PPO) that is (PEO-PPO-PEO).(Achouri et al., 2014). Cubosomes are best suitable for poorly water soluble drugs, and they increase solubilisation of drug and m aintain controlled release.(Boyd, 2003) Rifampicin is the only lipophilic drug in all anti-TB first-line drugs. This drug delivery system enhances drug solubility and bioavailability and reduces toxicity and maintains controlled release at the target site. In this study, we prepared rifampicin loaded cubosomes by hot melt method. The main objective of the study to reduce the dose and maintain controlled release, and it is also capable of increasing solubility and bioavailability of the drug. The optimized formulation ratio was fixed by the results obtained by varying dependent and independent variables using response surface methodology (RSM) with a 3 ² full factorial design. Materials Methods Rifampicin was obtained as a free sample from Lupin (Lupin pharmaceuticals, Pune), Peceol was purchased from and poloxamer 407 was purchased from and millipore water was used for all experiments. Preparation of rifampicin loaded cubosomes Rifampicin loaded cubosomes are prepared by using hot melt method.(Boyd, 2003). In this method, Peceol, poloxamer 407 and drug were taken as organic phase and mixed until the drug is completely entrapped in the dispersed phase. And then organic phase and aqueous phase (water) were heated at 70 ºC and aqueous phase was added slowly to organic phase under stirring. Then bulk cubic gel was fragmented by high speed homogenisation (Ultraturrax, 12000rpm) for 10 minutes and ultrasonication for 5minutes. The final dispersion was stored at room temperature. Experimental design References Achouri, D., Sergent, M., Tonetto, A., Piccerelle, P., Andrieu, V., Hornebecq, V., 2014. Self-assembled liquid crystalline nanoparticles as an ophthalmic drug delivery system. Part II: optimization of formulation variables using experimental design. Drug Dev. Ind. Pharm. 9045, 1–9. doi:10.3109/03639045.2014.884113 Argekar, A.P., Kunjir, S.S., Purandare, K.S., 1996. Simultaneous determination of rifampicin , isoniazid and pyrazinamid by high performance thin layer chromatography 14, 1645–1650. Boyd, B., 2003. Characterisation of drug release from cubosomes using the pressure ultrafiltration method. Int. J. Pharm. 260, 239–247. doi:10.1016/S0378-5173(03)00262-X Kaur, I.P., Singh, H., 2014. Nanostructured drug delivery for better management of tuberculosis. J. Control. Release 184, 36–50. doi:10.1016/j.jconrel.2014.04.009 Labuschagne, P.W., Adami, R., Liparoti, S., Naidoo, S., Swai, H., Reverchon, E., 2014. Preparation of rifampicin/poly(d,l-lactice) nanoparticles for sustained release by supercritical assisted atomization technique. J. Supercrit. Fluids 95, 106–117. doi:10.1016/j.supflu.2014.08.004 Moretton, M. a, Glisoni, R.J., Chiappetta, D. a, Sosnik, A., 2010. Molecular implications in the nanoencapsulation of the anti-tuberculosis drug rifampicin within flower-like polymeric micelles. Colloids Surf. B. Biointerfaces 79, 467–79. doi:10.1016/j.colsurfb.2010.05.016 Moualeu, D.P., Weiser, M., Ehrig, R., Deuflhard, P., 2015. Optimal control for a tuberculosis model with undetected cases in Cameroon. Commun. Nonlinear Sci. Numer. Simul. 20, 986–1003. doi:10.1016/j.cnsns.2014.06.037 Nguyen, T.-H., Hanley, T., Porter, C.J.H., Boyd, B.J., 2011. Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration. J. Control. Release 153, 180–6. doi:10.1016/j.jconrel.2011.03.033 Son, Y.-J., McConville, J.T., 2011. A new respirable form of rifampicin. Eur. J. Pharm. Biopharm. 78, 366–76. doi:10.1016/j.ejpb.2011.02.004 Sosnik, A., Carcaboso, A.M., Glisoni, R.J., Moretton, M. a, Chiappetta, D. a, 2010. New old challenges in tuberculosis: potentially effective nanotechnologies in drug delivery. Adv. Drug Deliv. Rev. 62, 547–59. doi:10.1016/j.addr.2009.11.023 Villemagne, B., Crauste, C., Flipo, M., Baulard, A.R., Dà ©prez, B., Willand, N., 2012. Tuberculosis: the drug development pipeline at a glance. Eur. J. Med. Chem. 51, 1–16. doi:10.1016/j.ejmech.2012.02.033 WHO 2014, n.d.

North Korea: Nuclear Friend or Foe? :: Nuclear proliferation

North Korea: Nuclear Friend or Foe? Introduction It is 2025. After decades of bickering and intense fighting, India and Pakistan finally break out into general war. Millions are killed in the nuclear exchange. Other countries are drawn into the fray, ultimately widening the landscape of war. The death toll reaches a billion lives. In essence, you are witnessing a nuclear holocaust. Fortunately, this is a completely fictitious event; something one would think was straight out of a movie. The scary part is that as more and more countries begin to acquire nuclear weapons, further nuclear research, and pursue other nuclear-related projects, this can be very real. It might happen in ten years, a few months, or even – tomorrow. The issue of nuclear proliferations is an issue of much concern by the United States. Since its creation back in the 1940s through the Manhattan project, the atomic bomb has been the bane of society, in terms of the level of potential threat it holds for the international community. The focus of this paper looks at U.S. policy towards nuclear proliferation, both past and present, with a special focus on the status of North Korea. For some analysts and many governmental officials, North Korea seems to be the next big threat to U.S. and international security. Proponents of this belief cite statements made by North Korea, efforts to enrich used fuel rods, and other pursuits to utilize nuclear power in some way or other. In an effort to really break down on a critical level the United States’ approach towards the country of North Korea, this paper examines not only the historical context of U.S./North Korea relations, but also the U.S. stance towards proliferation among such countries as Iran, Libya, Israel, India, Pakistan, and other countries. In using other countries to compare and contrast U.S. policy, hopefully this will bring about some sort of rationale behind the approach to North Korea. Understandably, the issue is way more complex than just a chosen stance towards each individual country. History, political balance, as well as, the intent of the U.S. administration at the time shape the policy instituted toward the particular country. A Colored History On June 27, 1950, President Harry S. Truman â€Å"authorized the use of American land, sea, and air forces in Korea; a week later, the United Nations placed the forces of 15 other member nations under U.

Conrad: Kill Whitey Essay

Indigenous peoples of Africa die every day because of war, famine, and disease largely due to the legacy of European imperialism. Joseph Conrad, who saw firsthand â€Å"the horror† (Conrad 154) of imperialism as a ship captain, sought to change public opinion and call attention to the atrocities committed. In Heart of Darkness, Conrad articulates his negative view of imperialism as oppressive and hypocritical through contrasts and parallels of Africa and Europe Conrad’s sympathetic portrayal of natives and demonizing portrayal of the Europeans makes the reader actively despise the institution of imperialism by forcing them to condemn the actions of Europeans in every circumstance presented. In his journey to the inner station, Marlow captains a ship that is crewed by cannibals and carries Pilgrims. Conrad sets up a decisive contrast as Marlow observes with puzzlement that the cannibals act restrained, even though the Pilgrims throw out their food. Marlow, acting as the European perspective â€Å"saw that something restraining, one of those human secret that baffle probability, had come into play here,† (Conrad 116). While this situation of native cannibals versus European pilgrims illustrates a distinct difference in behavior, other incidents stand out as well; most of Marlow’s encounters portray the natives not as villains, but as victims. At the central station he watches as a black man is beaten by whites for â€Å"[they] said he had caused the fire in some way; be that as it may, he was screeching most horribly,† (Conrad 92). Here, Marlow characteristically infused doubt as to the man’s guilt, through the â€Å"be that as it may† clause, that further shows victimization. But how much of this behavior is fiction? Avrom Fleishman writes that in his other works, Conrad consistently demonstrates how Europeans in their contact with natives show an emergence of â€Å"submerged barbarism† and that â€Å"whites become more savage than the savages,† (Fleishman 157). This pattern of role reversal allows Conrad to easily defame imperialists through their beastly and â€Å"Savage† actions. If Africa houses and nurtures evil, Conrad attempts to parallel it in Europe.  Before Marlow begins to tell his story the narrator remarks on his surroundings, frequently interlacing descriptions of settings with foreshadows of doom, making London and the Thames part of the world Marlow is about to take the boatmen into. The sun is described as being â€Å"stricken to death,† (Conrad 67) implying that evil lurks not just in and amongst the denizens of Africa, but here in Europe too in the relative safety of the Thames. Chinua Achebe in his indictment of Conrad as a racist admits a parallel between the Congo River and the Thames, stating â€Å"the Thames, too, ‘has been one of the darkest places on earth,'† (Achebe 1). The evil in Europe then must spread to its people. Kurtz, who embodies evil through his godlike control or hollowness, is both the most evil European and the most productive. Kurtz links ruthlessness to productivity and while his actions may only flourish in Africa, he still gathers ivory for Europe. By paralleling and linking the evil in Africa to Europe, Conrad poignantly shows the hypocrisy of the white view of black natives as savage. How can they be savage if the most evil person Africa is white? The hypocrisy of the imperialists extends beyond their perception of the natives; it surrounds all of their actions. In his essay of Conrad’s views of imperialism Cedric Watts describes the circumstances of Marlow’s visit to the central Station. On one side we see instances of the inefficiency, wastefulness and futility of the imperialists’ endeavours–objectless blasting, upturned trucks; and on the other side we see the price in human terms of these activities: the emaciated blacks of the chain-gang, starved slave labourers. The juxtaposition makes a telling indictment of the folly, hypocrisy and callousness of the so-called emissaries of progress, ‘pilgrims’ who, nominally Christians, are idolaters before ivory. (Watts 181) Watts’ charge illustrates view that all Europeans are alien to the region and do not belong. By making them seem useless and more as a burden, Conrad makes the reader feel that the Europeans should leave Africa; and convincing them in the context of Heart of Darkness will eventually help Conrad spread his anti-imperialist message. Throughout Heart of Darkness Conrad reinforces the Europeans as being outsiders, intruders, and the prime evildoers in the novel. He articulates his negative view of imperialism through contrasts and parallels of Africa and Europe: through his contrast of the cannibals and pilgrims, the role of Kurtz, and his portrayal of the imperialists. Conrad observed the horror of Imperialism and set out to fight it being sewing seeds of discontent in his readers’ feelings about the issue cementing Heart of Darkness as a prime example of an anti-imperialist text. Works Cited Achebe, Chinua. â€Å"An Image of Africa† The Massachusetts Review Vol. XVIII No. 4 Winter 1977: 782-94. Exploring Novels. Student Resource Center, Detroit. 29 Nov. 2003 . Conrad, Joseph. Heart of Darkness. New York: Signet Classic, 1950. Fleishman, Avrom. â€Å"The Politics of Imperialism.† Conrad’s Politics:Community and Anarchy in the fiction of Joseph Conrad. Baltimore: Johns Hopkins UP, (1967): 89-96. Rpt. in Readings on Heart of Darkness. Ed. Clarice Swisher. San Diego: Greenhaven Press, 1999. 156-161. Watts, Cedric. â€Å"Indirect Methods Convey Conrad’s View’s of Imperialism.† A Preface to Conrad. London: Longman Group UK Ltd., (1993). Rpt. in Readings on Heart of Darkness. Ed. Clarice Swisher. San Diego: Greenhaven Press, 1999. 177-183.

The Hunger Games by Suzanne Collins - 1257 Words

The Hunger Games is a fantastic science fiction novel by the great and renowned American writer Suzanne Collins. This book is written in the voice of sixteen year-old Katniss Everdeen, who lives in the nation of Panem in North America. The Capitol is considered as the highly advanced metropolis as because this capitol exercises political control on rest of the nation. The Hunger Games in the book is the annual event in which one boy and one girl aged twelve to eighteen from each of the 12 districts that surrounds the Capitol are selected by lottery so that they can compete in a televised battle to the death. Collins has successfully created a brilliant dystopian world that gives a treat to the readers. Reading the book provides concise as†¦show more content†¦However, her life as a tribute becomes more complicated by the other tribute from districts twelve. Peeta Mellark who is the son of baker that Katniss owes a favor to because of his kindness that he showed her when she was in need and was most desperate and her family’s survival was at stake. However, Katniss knows that then her survival would mean his death. In order to get involved in the ceremony Katniss is whisked away from loved one, her family and Gale who is her best friend and hunting partner. Katniss is being prepped and primped for participating in the Games. She and Peeta are to be mentored by Haymitch who is very reluctant and regarded as the inadequate mentor, so finally Katniss realizes that she must rely on her own abilities and strengths for survival. The book Hunger Games is very appealing and compelling to the readers and makes the reader curious as they want to read the next book immediately to find out what has happened to Katniss and Peeta. The novel has very appealing themes as it talks about the issues that are tackles† such as the utter penury, oppression, starvation and the other effects of war among the people as they are being forced to participate in the games that are meant for entertainment and are deadly in nature. The novel deals with the struggle for the self-preservationShow MoreRelatedThe Hunger Games By Suzanne Collins3246 Words   |  13 PagesStudy Unit The Hunger Games by Suzanne Collins and Steven Galloway’s The Cellist of Sarajevo demonstrates the way in which people are affected by war, and a brutal dictatorship. The authors illustrates the main purpose for writing their novel through the use of imagery, characterization, foreshadowing, flashback, similes, and symbolism. Suzanne Collins and Steven Galloway use imagery and characterization to vividly describe the effects and outcomes of war and dictatorship. Suzanne Collins portrays,Read MoreThe Hunger Games By Suzanne Collins1352 Words   |  6 PagesThe movie or the book the Hunger Games came out with a bang when it first hit theaters or the shelves of the bookstores. It was dubbed as one of the best films or books to read, interestingly enough it was a remake of the stories or myths most people heard when they were younger, but modernized and turned into a collage of all the best roman and Greek stories. Suzanne Collins brilliantly combined the Greek and Roman influences to make the movie/book unforgettable. By using stories from the romansRead MoreThe Hunger Games By Suzanne Collin899 Words   |  4 Pages Suzanne Collin’s â€Å"Hunger Games† seems to be about a dystopian society struggle to become a utopia. However, when the readers read further in to the book or watches the movie one can see that is about all the characters that make use human. As human, we feel the need to build an ethical framework based on our needs for authority rather than tradition. The Capitol in the Hunger Games exploits human needs to keep authority in place. After rising seas and poverty consumed much of the land, the CapitolRead MoreThe Hunger Games By Suzanne Collins1419 Words   |  6 Pagesemotional atmosphere within a dystopian state, there exists an absence of feeling which competes for dominance. Suzanne Collins’ demonstrates this competing apathetic mood in her novel, The Hunger Games, through the citizens of the divided dystopia of Panem. This essay will analyze the origins and influence of apathy on a people and an individual, in both a political and personal sense. Collins’ main argument, that citizens’ facing governmental oppression can either become compliant with apathy, or, insteadRead MoreThe Hunger Games By Suzanne Collins854 Words   |  4 PagesIn a place where poverty is prevalent and a country is ruled b y a tyrannical dictator is it possible for an individual to trust others when their own life is always at stake? In the book The Hunger Games by Suzanne Collins, the main character Katniss Everdeen is a survivor. In the novel she is put into an arena to compete against twenty-three other tributes to the death. This is not the only time during which she has to fend for herself; at home she had to care for her family and keep them aliveRead MoreThe Hunger Games by Suzanne Collins710 Words   |  3 Pages‘’The hunger games’’ is a novel written by Suzanne Collins, published in 2008. The genre of the book is thriller/survival, and is written over 27 chapters with 454 pages. In this analysis, I will tell you about how the main character Katniss changes through the novel, and tell you a little about the central characters that plays an important role for her. ‘’The Hunger Games’’, is set in the future in the country Panem, and is about the sixteen-year-old girl, Katniss Everdeen. Panem is divided intoRead MoreThe Hunger Games By Suzanne Collins986 Words   |  4 PagesThe Hunger Games by Suzanne Collins is about a sixteen year old girl named Katniss and how she needs to fight for her life. The Hunger Games takes place in an arena in the Capitol of Panem. There are 24 tributes, two from each District. The games were created to punish the Twelve Districts for trying to create an uprising against the Capitol. Suzanne Collins book could be compared to the United States and how people obsess with the way they look, discrimination is still occurring, and how the governmentRead MoreThe Hunger Games By Suzanne Collins3514 Words   |  15 PagesThe Hunger Games is a science fiction, dystopian post-apocalyptic series that takes place in a futuristic North American nation called Panem. The film series is based on the nov el series of the same title written by Suzanne Collins. Many who watch the films view them as an action-packed adventure series, but The Hunger Games, like many other dystopian films, feature social and political subjects that relate back to past and present culture. Dystopian films like the Hunger Games provide messages,Read MoreThe Hunger Games By Suzanne Collins1487 Words   |  6 PagesMy first text is The Hunger Games which is written by Suzanne Collins and it was written in September 14 2008; was set in the future, around the year 2087. My second text which is 1984, which is written by George Orwell and was written on Wednesday June 8 1949 and it was set in 1948. There are many themes in the book hunger games such as ‘the inequality between rich and poor’, ‘suffering as environment’ and ‘the importance of appearances’. In 1984 there is also many themes portrayed such as ‘theRead MoreThe Hunger Games By Suzanne Collins2436 Words   |  10 PagesThe Hunger Games is a science fiction and adventure film, based on the novel written by Suzanne Collins, which explores concepts of Marxism and numerous aspects of its principles through the dystopian world of Panem. The Hunger Games follows Marxist theories on bourgeoisie and proletariat class structure as well as capitalist production and the distribution of good. Thelma and Louise, a 1991 film directed by Ridley Scott, is often referred to by critics as â€Å"the ultimate feminist film†. This film