Sustained-release hydrogels of ivermectin as alternative systems to improve the treatment of cutaneous leishmaniasis

2020 ◽  
Vol 11 (12) ◽  
pp. 779-790
Author(s):  
Analía I Romero ◽  
Alicia G Cid ◽  
Nicolás E Minetti ◽  
Cintia A Briones Nieva ◽  
María F García Bustos ◽  
...  

Background: Leishmaniasis is a neglected tropical disease and its cutaneous form manifests as ulcers or nodules, generally in exposed parts of the body. This work aimed to develop ivermectin (IVM) thermosensitive hydrogels as topical formulations to improve cutaneous leishmaniasis treatment. Materials & methods: Hydrogels based on poloxamers 407 and 188 with different concentrations of IVM were prepared and rheologically characterized. The IVM release profiles were obtained and mathematically analyzed using the Lumped model. Results: The formulation containing 1.5% w/w of IVM presented an adequate gelling temperature, an optimal complex viscosity and elastic modulus. Hydrogels allowed to modulate the release of IVM. Conclusion: IVM thermosensitive hydrogels can be considered a valuable alternative to improve the treatment of cutaneous leishmaniasis.

INDIAN DRUGS ◽  
2014 ◽  
Vol 51 (05) ◽  
pp. 5-13
Author(s):  
Akanksha Bhatt ◽  
◽  
Ganesh Kumar ◽  
Preeti Kothiyal

Visceral leishmaniasis is a protozoan disease which infects the macrophages of body and Kupffer cells (KCs) in the liver resident macrophages, which constitute 80% of tissue macrophages of the body. KCs are the first cellular protective line in liver sinusoid, which come into contact with gut-derived pathogenic microbes, microbial debris and senescent erythrocytes and impede the exogenous materials by producing cytokines and directly phagocytosing and degrading them. Visceral leishmaniasis (VL) is a vector-borne disease and it is widely accredited that the frequency as well as transmission dynamics of VL is closely interrelated to socioeconomic, climatic, and environmental factors. Macrophages act so as to secrete IL-1, TNF and IL-6 at the time of injury and infection, and process and present antigen to help T cells. Mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in tissue. Macrophages are dispersed throughout the body and take up residence in some tissues. Human leishmanial infections may manifest in any of the four most common forms. Depending on the causative species, it can manifest as cutaneous leishmaniasis mucocutaneous leishmaniasis, visceral leishmaniasis or diffused cutaneous leishmaniasis. The cutaneous form of the disease accounts for more than 50% of new cases of leishmaniasis. The current method of VL diagnosis involves evaluating clinical symptoms that include fever for more than 2 week, the presence of splenomegaly and a positive serological rK39 immunochromatographic rapid diagnostic test (RDT). The rK39 RDT is used to detect the presence of antibodies against the Leishmania antigen K39 that contains a repetitive 39 amino acid sequence from the kinesin protein.


Author(s):  
L. Saeednia ◽  
A. Usta ◽  
R. Asmatulu

Hydrogels are the promising classes of polymeric drug delivery systems with the controlled release rates. Among them, injectable thermosensitive hydrogels with transition temperature around the body temperature have been wildly considered. Chitosan is one of the most abundant natural polymers, and its biocompatibility and biodegradability makes it a favorable thermosensitive hydrogel that has been attracted much attention in biomedical field worldwide. In this work, a thermosensitive and injectable hydrogel was prepared using chitosan and β-glycerophosphate (β-GP) incorporated with an antibacterial drug (gentamycin). This drug loaded hydrogel is liquid at room temperature, and becomes more solidified gel when heated to the body temperature. Adding β-GP into chitosan and drug molecules and heating the overall solution makes the whole homogenous liquid into gel through a 3D network formation. The gelation time was found to be a function of temperature and concentration of β-GP. This thermosensitive chitosan based hydrogel system was characterized using FTIR and visual observation to determine the chemical structure and morphology. The results confirmed that chitosan/(β-GP) hydrogels could be a promising controlled-release drug delivery system for many deadly diseases.


2015 ◽  
Vol 25 (2) ◽  
pp. 78-80
Author(s):  
Abdur Rahim ◽  
Md Moniruzzan ◽  
Rashedul Hassan ◽  
Monira Sarmin ◽  
Md Abdullah Yusuf ◽  
...  

Cutaneous leishmaniasis is rare in Bangladesh although very few case reports are seen since last few years. But Visceral Leishmaniasis (kala azar) and PKDL are common in this region. In country like ours where tuberculosis and leprosy are more prevalent Cutaneous Leishmaniasis is very likely to be mistreated as Cutaneous tuberculosis especially lupus vulgaris or leprosy. Cases of Cutaneous Leishmaniasis (CL) are usually imported to Bangladesh from other endemic countries. A patient from an endemic area of Cutaneous Leishmaniasis, a non-healing nodulo-ulcerative lesion on exposed part of the body, dermal infiltration with lymphocytes, histiocytes and plasma cells and demonstration of intracellular parasites in lesional skin establish the diagnosis of Cutaneous Leishmaniasis. We present a case of Cutaneous Leishmaniasis in a Bangladeshi adult working in Saudi Arabia for more than 15 years. He presented with multiple ulcerative lesions on nasal bridge, right ear lobule and dorsum of right ring finger. The patient’s clinical history, morphology of the lesions and laboratory analysis were consistent with Cutaneous Leishmaniasis, a rare entity for Bangladesh.Bangladesh J Medicine Jul 2014; 25 (2) : 78-80


1975 ◽  
Vol 41 (1) ◽  
pp. 291-298 ◽  
Author(s):  
Gerald A. Winer

First graders were tested on trials requiring the discrimination and transposition of right-left relations, with stimuli similar to (dolls) or different from (toy planes) the body. On an initial series of training and practice trials children were allowed to respond to body and external objects as referents providing right-left cues. A later series of test trials was then used to determine the referent the child actually preferred. Results of the test trials indicated that 24 children tested with the dolls preferred the body as referent, while 24 children tested with planes preferred the external referent. The results were interpreted as suggesting two alternative systems through which children develop an undersranding of right-left relations and possibly other concepts as well.


Leprosy ◽  
2020 ◽  
pp. 1-19
Author(s):  
Charlotte A. Roberts

This chapter introduces leprosy, an infection that is still misunderstood and considered a neglected tropical disease but declining in frequency, according to the World Health Organization. The bacteria that cause leprosy, Mycobacterium leprae and Mycobacterium lepromatosis, are outlined, as well as how a relative strength of a person’s immune system determines how leprosy affects the body. Although leprosy is curable, associated stigma and disability remain common challenges for people with the disease in parts of the world. The goals and structure of the book are outlined, ten myths that still pervade society at large are listed, and the use of the word “leper” discussed. Based on World Health Organization data, the chapter also explores the frequency of leprosy today, where the infection remains a challenge, and the history of detecting and reporting evidence for leprosy in living populations. Finally, the reasons why bioarchaeologists have an interest in this infection are explored.


2006 ◽  
Vol 39 (4) ◽  
pp. 323-326 ◽  
Author(s):  
Manoel Paes de Oliveira-Neto ◽  
Marise da Silva Mattos

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86% efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.


2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Masoud Doroodgar ◽  
Moein Doroodgar ◽  
Abbas Doroodgar

The leishmaniases are parasitic diseases that are transmitted to humans by infected female sandflies. Cutaneous leishmaniasis (CL) is one of 3 main forms of the disease. CL is the most common form of the disease and is endemic in many urban and rural parts of Iran and usually caused by two species ofLeishmania:L. majorandL. tropica.We report a case of unusual leishmaniasis with 25 lesions on exposed parts of the body and right eyelid involvement (ocular leishmaniasis). The patient was a 75-year-old male farmer referred to health care center in Aran va Bidgol city. The disease was diagnosed by direct smear, culture, and PCR from the lesions. PCR was positive forLeishmania major.


2014 ◽  
Vol 136 (8) ◽  
Author(s):  
Antonio Campo ◽  
Jaime Sieres

Within the framework of the potent lumped model, unsteady heat conduction takes place in a solid body whose space–mean temperature varies with time. Conceptually, the lumped model subscribes to the notion that the external convective resistance at the body surface dominates the internal conductive resistance inside the body. For forced convection heat exchange between a solid body and a neighboring fluid, the criterion entails to the lumped Biot number Bil=(h¯/ks)(V/A)<0.1, in which the mean convective coefficient h¯ depends on the impressed fluid velocity. However, for natural convection heat exchange between a solid body and a fluid, the mean convective coefficient h¯ depends on the solid-to-fluid temperature difference. As a consequence, the lumped Biot number must be modified to read Bil=(h¯max/ks)(V/A)<0.1, wherein h¯max occurs at the initial temperature Ti for cooling or at a future temperature Tfut for heating. In this paper, the equivalence of the lumped Biot number criterion is deduced from the standpoint of the solid thermal conductivity through the solid-to-fluid thermal conductivity ratio.


2008 ◽  
Vol 52 (8) ◽  
pp. 2855-2860 ◽  
Author(s):  
Thomas P. C. Dorlo ◽  
Pieter P. A. M. van Thiel ◽  
Alwin D. R. Huitema ◽  
Ron J. Keizer ◽  
Henry J. C. de Vries ◽  
...  

ABSTRACT The pharmacokinetics of miltefosine in leishmaniasis patients are, to a great extent, unknown. We examined and characterized the pharmacokinetics of miltefosine in a group of patients with Old World (Leishmania major) cutaneous leishmaniasis. Miltefosine plasma concentrations were determined in samples taken during and up to 5 months after the end of treatment from 31 Dutch military personnel who contracted cutaneous leishmaniasis in Afghanistan and were treated with 150 mg miltefosine/day for 28 days. Samples were analyzed with a validated liquid chromatography-tandem mass spectrometry assay with a lower limit of quantification (LLOQ) of 4 ng/ml. Population pharmacokinetic modeling was performed with nonlinear mixed-effect modeling, using NONMEM. The pharmacokinetics of miltefosine could best be described by an open two-compartment disposition model, with a first elimination half-life of 7.05 days and a terminal elimination half-life of 30.9 days. The median concentration in the last week of treatment (days 22 to 28) was 30,800 ng/ml. The maximum duration of follow-up was 202 days after the start of treatment. All analyzed samples contained a concentration above the LLOQ. Miltefosine is eliminated from the body much slower than previously thought and is therefore still detectable in human plasma samples taken 5 to 6 months after the end of treatment. The presence of subtherapeutic miltefosine concentrations in the blood beyond 5 months after treatment might contribute to the selection of resistant parasites, and moreover, the measures for preventing the teratogenic risks of miltefosine treatment should be reconsidered.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242494
Author(s):  
Aicha Boukthir ◽  
Jihene Bettaieb ◽  
Astrid C. Erber ◽  
Hind Bouguerra ◽  
Rym Mallekh ◽  
...  

Although non-fatal and mostly self-healing in the case of Leishmania (L.) major, cutaneous leishmaniasis (CL) is mainly treated to reduce lesion healing time. Less attention is paid to the improvement of scars, especially in aesthetically relevant areas of the body, which can dramatically affect patients’ wellbeing. We explored patients’ perspectives about treatment options and the social and psychological burden of disease (lesion and scar). Individual in-depth interviews were conducted with ten confirmed CL patients at two L. major endemic sites in Southern Tunisia (Sidi Bouzid and Gafsa). Participants were selected using a sampling approach along a spectrum covering e.g. age, sex, and clinical presentation. Patients’ experiences, opinions and preferences were explored, and their detailed accounts gave an insight on the impact of CL on their everyday lives. The impact of CL was found to be considerable. Most patients were not satisfied with treatment performance and case management. They expected a shorter healing time and better accessibility of the health system. Tolerance of the burden of disease was variable and ranged from acceptance of hidden scars to suicidal thoughts resulting from the fear to become handicapped, and the stress caused by close relatives. Some believed CL to be a form of skin cancer. Unexpectedly, this finding shows the big gap between the perspectives of patients and assumptions of health professionals regarding this disease. This study provided valuable information for better case management emphasizing the importance of improving communication with patients, and accessibility to treatment. It generated context-specific knowledge to policy makers in Tunisia to implement effective case management in a country where access to treatment remains a challenge due to socio-economic and geographic barriers despite a long tradition in CL control.


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