Mannosylated Thiolated Polyethylenimine Nanoparticles for the Enhanced Efficacy of Antimonial Drug Against Leishmaniasis

Sarwar, Hafiz Shoaib; Ashraf, Sehreen; Akhtar, Sohail; Sohail, Muhammad; Hussain, Syed Zajif; Rafay, Muhammad; Yasinzai, Masoom; Hussain, Irshad; Shahnaz, Gul

doi:10.2217/nnm-2017-0255

Cited by 44 publications

(17 citation statements)

References 26 publications

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“…To overcome the failure of anti-leishmanial drug therapies, the design and development of pertinent drugcarrier systems are of immediate importance. Several drug delivery systems have been developed against VL with enhanced efficacy and reduced toxicity concerns [18][19][20][21][22] . In in vivo, the efficacy of the drug is not solely dependent on its physico-chemical properties, but also the carrier system, which could enhance the bioavailability, concede a localized and controlled release of the drug which endow to the explicit requirements of therapy to maximize efficacy, patient safety and compliance 23 .…”

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confidence: 99%

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Parvez

Yadagiri

Gedda

et al. 2020

Sci Rep

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The development of an effective oral therapeutics is an immediate need for the control and elimination of visceral leishmaniasis (VL). We exemplify the preparation and optimization of 2-hydroxypropyl-β-cyclodextrin (HPCD) modified solid lipid nanoparticles (SLNs) based oral combinational cargo system of Amphotericin B (AmB) and Paromomycin (PM) against murine VL. The emulsion solvent evaporation method was employed to prepare HPCD modified dual drugloaded solid lipid nanoparticles (m-DDSLNs). The optimized formulations have a mean particle size of 141 ± 3.2 nm, a polydispersity index of 0.248 ± 0.11 and entrapment efficiency for AmB and PM was found to be 96% and 90% respectively. The morphology of m-DDSLNs was confirmed by scanning electron microscopy and transmission electron microscopy. The developed formulations revealed a sustained drug release profile upto 57% (AmB) and 21.5% (PM) within 72 h and were stable at both 4 °C and 25 °C during short term stability studies performed for 2 months. Confocal laser scanning microscopy confirmed complete cellular internalization of SLNs within 24 h of incubation. In vitro cytotoxicity study against J774A.1 macrophage cells confirmed the safety and biocompatibility of the developed formulations. Further, m-DDSLNs did not induce any hepatic/renal toxicities in Swiss albino mice. The in vitro simulated study was performed to check the stability in simulated gastric fluids and simulated intestinal fluids and the release was found almost negligible. The in vitro anti-leishmanial activity of m-DDSLNs (1 µg/ml) has shown a maximum percentage of inhibition (96.22%) on intracellular amastigote growth of L. donovani. m-DDSLNs (20 mg/kg × 5 days, p.o.) has significantly (P < 0.01) reduced the liver parasite burden as compared to miltefosine (3 mg/kg × 5 days, p.o.) in L. donovani-infected BALB/c mice. This work suggests that the superiority of as-prepared m-DDSLNs as a promising approach towards the oral delivery of anti-leishmanial drugs. Visceral leishmaniasis (VL), also known as Kala-Azar is the most severe form of leishmaniasis, a neglected tropical disease caused by the protozoan parasite Leishmania donovani, The disease is transmitted to human host by the bite of an infected female haemo-flagellate sand fly 1. According to WHO, 0.5-0.9 million new VL cases are reported every year, > 95% of which occur in ten countries Bangladesh,

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confidence: 99%

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Parvez

Yadagiri

Gedda

et al. 2020

Sci Rep

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“…In vitro antileishmanial activity was performed with Leishmania tropica khw23 strain [18]. The Leishmanial parasite was kindly provided by Dr. Gul Shahnaz and protocol was followed as described [18].…”

Section: Methodsmentioning

confidence: 99%

Phytochemical, in-vitro biological and chemo-preventive profiling of Arisaema jacquemontii Blume tuber extracts

Tabassum

Zia

Blanco

et al. 2019

BMC Complement Altern Med

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Background Arisaema jacquemontii is traditionally used in treatment of different diseases. In this study, phytochemical, in vitro biological and chemo-preventive screening of A. jacquemontii was carried out to explore its pharmacological potential. Methods The dried tuber of A. jacquemontii was extracted in 11 organic solvent mixture of different polarity. The extracts were screened for phytochemical assays (phenolics and flavonoids), antioxidants potential (free radical scavenging activity, total antioxidant activity, reducing power), biological activities (antibacterial, antifungal, cytotoxic, antileishmanial, protein kinase inhibition), and chemopreventive activities using different cell lines through standard protocols. Results Significant amount phenolic contents were determined in EtOH and MeOH extracts (210.3 ± 3.05 and 193.2 ± 3.15 μg GAE/mg, respectively). Maximum flavonoid content was determined in MeOH extract (22.4 ± 4.04 μg QE/mg). Noteworthy, DPPH scavenging activity was also recorded for MeOH extract (87.66%) followed by MeOH+EtOAc extract (85.11%). Considerable antioxidant capacity (7.8 ± 0.12 μg AAE/mg) and reducing power (3.1 ± 0.15 μg AAE/mg) was observed in extract of MeOH. The LC50 against brine shrimp and leishmanial parasite was found 9.01 and 12.87 μg/mL for n-Hex and CHCl3 extracts, respectively. The highest zone of inhibition against Streptomyces hyphae formation (12.5 ± 1.77 mm) by n-Hex extract. Growth zone of inhibition 13.8 ± 1.08 mm was recorded for EtOAc and MeOH extracts, respectively against Micrococcus luteus while 10.0 ± 0.11 mm for MeOH extract against Aspergillus flavus. In-vitro cytotoxic assay showed that n-Hex extract had higher cytotoxicity against DU-145 prostate cancer and HL-60 cancer cell lines. NF-kB and MTP potential showed 34.01 and 44.87 μg/mL for n-Hex and CHCl3 extracts, respectively in chemo-preventive potential. Conclusion The study concludes that Arisaema jacquemontii bears significant phytochemical activity and pharmacological activities, this plant can be further explored for isolation of active component against a number of aliments.

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“…Mannosylated thiolated chitosan (MTC) and mannosylated thiolated chitosan-polyethyleneimine (MTCE) were also used to incorporate antimonial compounds and analyze their antileishmanial activity [ 47 ]. While meglumine antimoniate-loaded nanoparticles inhibited the trypanothione reductase with a K i at 2 µM, their macrophage uptake was 33.7- and 18.9-fold higher with MTCE and MTC, respectively, in comparison to Glucantime ® .…”

Section: Chitosan-based Drug Loaded Formulations For the Chemothermentioning

confidence: 99%

Chitosan Contribution to Therapeutic and Vaccinal Approaches for the Control of Leishmaniasis

2020

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The control of leishmaniases, a complex parasitic disease caused by the protozoan parasite Leishmania, requires continuous innovation at the therapeutic and vaccination levels. Chitosan is a biocompatible polymer administrable via different routes and possessing numerous qualities to be used in the antileishmanial strategies. This review presents recent progress in chitosan research for antileishmanial applications. First data on the mechanism of action of chitosan revealed an optimal in vitro intrinsic activity at acidic pH, high-molecular-weight chitosan being the most efficient form, with an uptake by pinocytosis and an accumulation in the parasitophorous vacuole of Leishmania-infected macrophages. In addition, the immunomodulatory effect of chitosan is an added value both for the treatment of leishmaniasis and the development of innovative vaccines. The advances in chitosan chemistry allows pharmacomodulation on amine groups opening various opportunities for new polymers of different size, and physico-chemical properties adapted to the chosen routes of administration. Different formulations have been studied in experimental leishmaniasis models to cure visceral and cutaneous leishmaniasis, and chitosan can act as a booster through drug combinations with classical drugs, such as amphotericin B. The various architectural possibilities given by chitosan chemistry and pharmaceutical technology pave the way for promising further developments.

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Mannosylated Thiolated Polyethylenimine Nanoparticles for the Enhanced Efficacy of Antimonial Drug Against Leishmaniasis

Abstract: These results encouraged the concept that TR and P-gp inhibition by the use of thiomers improves the therapeutic efficacy of antimonial drugs.

Cited by 44 publications

References 26 publications

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Modified solid lipid nanoparticles encapsulated with Amphotericin B and Paromomycin: an effective oral combination against experimental murine visceral leishmaniasis

Phytochemical, in-vitro biological and chemo-preventive profiling of Arisaema jacquemontii Blume tuber extracts

Chitosan Contribution to Therapeutic and Vaccinal Approaches for the Control of Leishmaniasis

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