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Macrophage Targeting: A Promising Strategy for Delivery of Chemotherapeutics in Leishmaniasis and Other Visceral Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Jaya Gopal Meher, Pankaj K. Singh, Yuvraj Singh, Mohini Chaurasia, Anita Singh, Manish K. Chourasia
Chemotherapy in any disease has its limitations and associated adverse effects. In case of leishmaniasis the existing chemotherapeutics have comparatively greater challenges: severe adverse effect, low cure rate as well as the most frightening, drug resistance. Whether it is antimonials, amphotericin B or orally active miltefosine, all reported antileishmanial drugs cause musculoskeletal pain, gastrointestinal disturbances, hypersensitivity, cardiotoxicity, renal failure etc. Long non-ambulatory administrative procedures pose additional discomfort to patients who are already distressed by unwanted adverse effects. Treatment failure is also sometimes encountered. In some parts of Asian countries like India, up to 65% of human treatment cases are found to be unresponsive to antimonials (Sundar, 2001). Investigational reports on such matters suggest a number of reasons viz. expression of multidrug resistance and efflux transporters, down-regulation of aquaporins, overproduction of thiol metabolizing enzyme. Recently, aberrant alteration in the sterol profiles of Leishmania parasite has been noticed where the cholesta–5,7,24-trien–3-ol is observed to be in membrane of parasite instead of ergosterol. This has significantly diminished selectivity of the gold standard drug amphotericin B. Miltefosine, is also on the verge of drug resistance, the reasons for which might be attributed to its long half-life as well as mutations in P-glycoprotein-LdRos3 and LdMT that are directly related to uptake of drug. Drug resistance is also reported for paromomycin, where parasites are observed to develop changes such as up-regulation of glycolytic enzymes and ATP-Binding cassette transporters. These modifications in parasites are acquired progressively with multiple stimulatory factors like inadequate treatment, partial or incomplete treatment as well as long term therapeutic interventions (Yasinzai et al., 2013). Infectious disease tuberculosis requires simultaneous treatment with multiple drugs viz. rifampicin, isoniazid, ethambutol, pyrazinamide, streptomycin, fluoroquinolones, kanamycin, capreomycin, amikacin, viomycinetc for long periods of time. All these drugs are reported to cause an array of adverse drug reactions. Apart from the side effects, the causative organism Mycobacterium has either acquired full or is on the verge of acquiring resistance to most of the listed drugs. Mutation in various genes is known to be responsible for drug resistance in M. tuberculosis. So chemotherapy with the current therapeutics is a challenge. Furthermore role of efflux pumps and porins are also caused drug resistance (Köser et al., 2015). In all of the infectious diseases, co-infection with HIV is reported to aggravate the case and treatment becomes more challenging. In such situations the duration of therapy increases multiple times and the socio-economic conditions of patients, their homelessness, poverty, non-compliance to therapeutic schedule remain the main reason for failure in therapy and development of drug resistance. Often the bioavailability of these drugs at the target site is also uncertain. Conventional therapy underperforms in other visceral diseases like hepatic diseases and cardiovascular diseases too (Acevedo, 2015).
Approaches for designing and delivering solid lipid nanoparticles of distinct antitubercular drugs
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Mallikarjun Vasam, Rama Krishna Goulikar
Conventional therapeutic systems came into existence for the treatment of TB with anti-tubercular drugs. The five main types of drugs used in chemotherapy for tuberculosis are: First-line anti-tubercular drugs (Isoniazid, Rifampicin, Rifabutin, Ethambutol, and Pyrazinamide) work effectively against tuberculosis, while second-line anti-tubercular drugs (Ethionamide, Cycloserine) work well when first-line drugs fail due to drug resistance [4, 9]. In tuberculosis treatment, patients need to take four oral antibiotics every day for six to nine months. Generally, TB is treated in two steps: during the initial phase, most of the live bacilli are killed by treatment with four first-line antibiotics for two months. The second phase is called the continuation phase, in which rifampicin and isoniazid are used daily or three times a week for 4–6 months to kill the bacteria that survived the initiation phase [10], which has complicated long-term conventional treatment has lethal side effects of anti-tubercular drugs may cause poor patients’ compliance, which can lead to the growth of drug-resistant strains.
Molecular characterization and antimicrobial resistance profiles of Mycobacterium tuberculosis complex in environmental substrates from three dairy farms in Eastern Cape, South Africa
Published in International Journal of Environmental Health Research, 2021
Athini Ntloko, Martins Ajibade Adefisoye, Ezekiel Green
First-line anti-tuberculosis agents, including rifampicin, isoniazid, pyrazinamide and streptomycin or ethambutol, represent the standard treatment of TB. Routine monitoring of drug resistance in MTBC is important due to the limited availability of first-line treatment drugs, the high prices of second-line treatment, and a lack of facilities for the detection of multidrug resistance in Mycobacterium strains (MDR-TB) in many health care centres. A better knowledge of the resistance profiles will also provide useful empirical data for better treatment and management of TB, and facilitate epidemiological surveys. Moreover, environmental contamination with MTBC is considered a key factor in bTB persistence in the multiple-host-pathogen systems. This study, therefore, aimed to use molecular methods to detect and evaluate the antimicrobial susceptibility profile of MTBC in environmental substrates (soil, water and hayfeed) collected from three dairy farms in the Eastern Cape region of South Africa.