Mannosylated Thiolated Paromomycin-Loaded PLGA Nanoparticles for The Oral Therapy of Visceral Leishmaniasis

Afzal, Iqra; Sarwar, Hafiz Shoaib; Sohail, Muhammad; Varikuti, Sanjay; Jahan, Sarwat; Akhtar, Sohail; Yasinzai, Masoom; Satoskar, Abhay R.; Shahnaz, Gul

doi:10.2217/nnm-2018-0038

Cited by 52 publications

(26 citation statements)

References 36 publications

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“…As expected, in vitro macrophage uptake of L. donovani amastigote forms was better for MTC‐PLGA‐PM, with IC 50 0.09 μg/ml, result 36 times lower than the free drug. BALB/c mice treated with MTC‐PLGA‐PM (20 mg/kg) reduced the hepatic parasitic load 3.6 times more than the free drug (Afzal et al, 2019).…”

Section: Resultsmentioning

confidence: 99%

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

Souza

Costa

Silva

et al. 2020

Drug Development Research

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Considered prevalent in many countries on five continents, especially in low‐income regions, leishmaniasis is a neglected tropical disease classified by World Health Organization as one of the diseases for which the development of new treatments is a priority. It is an infectious disease caused by protozoa of the genus Leishmania, whose species may cause different clinical manifestations, such as cutaneous and visceral leishmaniasis (VL). Treatment is exclusively by drug therapy, as it has not been possible to develop vaccines yet. Currently available drugs are not fully effective in all cases; they have parenteral administration and exhibit a number of serious and very common adverse effects. The only oral drug available is expensive and it is not available in many endemic countries. Injectable administration is the main problem of treatments, since it requires patients to go to health centers, hospitalization and professional administration, which are conditions that are not adapted to the reality of the poverty conditions of patients with the disease. In this context, the development of an oral medicine has become a focus as it may solve many of these issues. Based on this scenario, this review aimed to investigate which therapeutic alternatives have been studied for the development of oral drugs directed to the treatment of human VL.

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Section: Resultsmentioning

confidence: 99%

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

Souza

Costa

Silva

et al. 2020

Drug Development Research

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“…From n values, it can be concluded that it followed (Fickian) diffusion mechanism i.e. gradual swelling of the TCS bandage released the ZnO-NPs via diffusin through polymer matrix [44]. From CS-Alg-ZnO release followed first order release mechanism with a maximum R 2 value of 0.93 and K 1 value of 0.01 [45].…”

Section: Resultsmentioning

confidence: 99%

ZnO-NPs embedded biodegradable thiolated bandage for postoperative surgical site infection: In vitro and in vivo evaluation

et al. 2019

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Post-operative surgical site infections (SSI) present a serious threat and may lead to complications. Currently available dressings for SSI lack mucoadhesion, safety, efficacy and most importantly patient compliance. We aimed to address these concerns by developing a bioactive thiolated chitosan-alginate bandage embedded with zinc oxide nanoparticles (ZnO-NPs) for localized topical treatment of SSI. The FTIR, XRD, DSC and TGA of bandage confirmed the compatibility of ingredients and modifications made. The porosity, swelling index and lysozyme degradation showed good properties for wound healing and biodegradation. Moreover, in-vitro antibacterial activity showed higher bactericidal effect as compared to ZnO-NPs free bandage. In-vivo wound healing in murine model showed significant improved tissue generation and speedy wound healing as compared to positive and negative controls. Over all, thiolated bandage showed potential as an advanced therapeutic agent for treating surgical site infections, meeting the required features of an ideal surgical dressing.

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“…Notably, macrophages are the central host cells which are infected by intracellular pathogens such as Leishmania and Toxoplasma, and it was well-established that mannosylated PM-SLN not only increase the bioavailability of PM, but also mannosylation enhance uptaking PM by macrophages (Frenz et al, 2015). In the study conducted by Afzal et al (2019), the maximum uptake was observed in macrophages that were treated by mannosylated thiolated chitosan-coated PM-loaded PLGA nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

“…This drug faces many challenges, such as quick renal excretion and short half-life in the blood circulation. Indeed, this drug is hydrophilic and has a high molecular weight that makes its uptake difficult (Ghadiri et al, 2012;Afzal et al, 2019). However, PM can be a good option for treatment of parasitic disease due to its safety, low cost, and short course therapy.…”

Section: Introductionmentioning

confidence: 99%

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

Khosravi

Rahimi

Doroud

et al. 2020

Front. Cell. Infect. Microbiol.

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Toxoplasma gondii is a zoonotic intracellular protozoan with worldwide distribution. Acute and severe toxoplasmosis are commonly reported in patients who suffer from acquired/congenital immune deficiency. This study aimed to synthesize mannosylated paromomycin-loaded solid lipid nanoparticles (PM-SLN-M) and to evaluate them on acute toxoplasmosis. SLN was synthesized and then loaded by 7 mg/mL paromomycin sodium. Mannose coating was performed, and after washing, the size, zeta potential, and loading percentage were calculated. To evaluate the cell toxicity, an MTT assay was performed on Vero cells by different concentrations (log 10 −1) of SLN, PM-SLN-M, and PM-SLN. In addition, the anti-Toxoplasma effects were also evaluated using trypan-blue staining and scanning electron microscopy (SEM). An MTT assay was also employed to evaluate the effects of PM and PM-SLN-M on intracellular Toxoplasma. A 6-month stability test of PM-SLN and PM-SLN-M represented that the characteristics all remained constant. The cell viability assay demonstrated that PM-SLN-M had lower cell toxicity (<20%) compared to PM-SLN (<30%) and PM (<40%). Statistical analysis showed that PM-SLN-M significantly killed ∼97.555 ± 0.629 (95% CI: 91.901 to 103.209; P < 0.05) of T. gondii tachyzoites. More than 50% of Toxoplasma-infected Vero cells remained viable in concentrations more than 0.07 µg/mL and 7 µg/mL of PM and PM-SLN-M, respectively. SEM analysis showed that T. gondii tachyzoites were changed in both size and morphology facing with PM-SLN-M. Our findings indicated that synthesized PM-SLN-M had anti-Toxoplasma activity without significant host cell toxicity at the highest concentration. Our study demonstrated that PM was able to kill intracellular Toxoplasma in lower concentration in comparison to PM-SLN-M, although PM-SLN-M showed lower cytotoxic effects on Vero cells.

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Mannosylated Thiolated Paromomycin-Loaded PLGA Nanoparticles for The Oral Therapy of Visceral Leishmaniasis

Cited by 52 publications

References 36 publications

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

Recent strategies for the development of oral medicines for the treatment of visceral leishmaniasis

ZnO-NPs embedded biodegradable thiolated bandage for postoperative surgical site infection: In vitro and in vivo evaluation

In vitro Evaluation of Mannosylated Paromomycin-Loaded Solid Lipid Nanoparticles on Acute Toxoplasmosis

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