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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
TLRs, a major class of proteins, also known as immune receptors are a very crucial and abundantly found receptors in immune cells including macrophages. There are 12 TLRs identified in mammals and amongst them TLRs 1–9 are conserved in human beings. Further, these TLRs are located at both extracellular (TLRs–1,–2,–4,–5,–6 and −11) and intracellular (TLRs–3,–7,–8,–9 and −13) regions of the cells and are able to recognize the pathogens at the outer cellular surface or even in the endosomal compartment. After recognizing pathogens, TLRs recruit adaptor proteins (MyD88 or TRIF) and consequently lead to a cascade of cellular events that cause phagocytosis. There are a number of ligands for the TLRs viz. triacyl lipopeptides, LPS, lipoproteins, profilin, alginate, chitosan, and many more that can be employed to target TLRs (Singh et al., 2012). The TLRs have been explored for vaccine delivery and immunotherapy against leishmaniasis. Raman et al. have developed an immunotherapeutic by employing the TLRs-synergy concept for improved immuno-response against cutaneous leishmaniasis. They have selected leishmania poly-protein vaccine (L110f) and combined with TLR4 agonist (monophosphoryl lipid A), and/or TLR9 agonist (CpG) and evaluated them against leishmaniasis. Researchers observed in their in vivo studies that a combination of three performed best against cutaneous leishmaniasis by boosting T cells, reducing parasite burden as well as lesions (Raman et al., 2010). Heuking et al. have worked on development of DNA vaccines for tuberculosis by using TLR2 agonist. They have employed chitosan polymer as a mucoadhesive material and complexed it with TLR2 agonist and plasmid DNA that can act in multiple way by imparting muco-adhesion for enhanced mucosal delivery as well as protection of DNA from degradative factors (Heuking et al., 2009).
Co-delivery of trifluralin and miltefosin with enhanced skin penetration and localization in Leishmania affected macrophages
Published in Journal of Dispersion Science and Technology, 2022
Cutaneous leishmaniasis (CL), is a protozoal skin infection caused by sand fly, associated with cutaneous nodules and diffused skin ulceration.[1] Although CL is not fatal, yet concomitant with scare mark on the lesion site, which is mostly on open areas of the body, and thus leads to social complications including, mental depression and inferiority complex.[2] Currently, this disease is spreading globally encountering 1 million cases every year in around 90 countries.[3] Unfortunately, no vaccine is developed so far against CL. Thus, chemotherapy is the lone choice for management of the Leishmania infection. Among the available chemotherapeutic agents for CL, most of them have poor cure rate owing to the growing resistance, high cost, toxicities and painful drug delivery.[4,5] Moreover, monotherapies for CL management are associated with longer treatment tenacity and partial efficacy.
Polyelectrolytic gelatin nanoparticles as a drug delivery system for the promastigote form of Leishmania amazonensis treatment
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Catarina de Souza, Janicy A. Carvalho, Alexandro S. Abreu, Lucas P. de Paiva, Jéssica A. R. Ambrósio, Milton Beltrame Junior, Marco A. de Oliveira, Josane Mittmann, Andreza R. Simioni
Cutaneous leishmaniasis (CL) is a neglected tropical disease and it is characterized by single or multiple lesions in the skin or in the mucosa tissues which develop into oral, nasal and pharyngeal destruction [1]. According to the World Health Organization (WHO), it is endemic in 98 countries and territories, with an estimate number of 350 million people in risk of infection. In addition, 12 million people are infected and there is the prediction of 45 million new cases and 20,000 to 30,000 deaths each year [2].