Novel Nanosized Chitosan-Betulinic Acid Against Resistant Leishmania Major and First Clinical Observation of such parasite in Kidney

Mehrizi, Tahereh Zadeh; Ardestani, Mehdi Shafiee; Hoseini, Mostafa Haji Molla; Khamesipour, Ali; Mosaffa, Nariman; Ramezani, Amitis

doi:10.1038/s41598-018-30103-7

Cited by 32 publications

(23 citation statements)

References 49 publications

(106 reference statements)

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“…The nanoparticles were characterized using SEM, TEM, AFM, FTIR and H-NMR methods according to the previous study 34…”

Section: Methodsmentioning

confidence: 99%

Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of Leishmania major: real-time PCR assay plus

Mehrizi¹,

Khamesipour²,

Ardestani³

et al. 2019

IJN

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BackgroundAmphotericin B (Amp) and Betulinic acid (BA) as antileishmanial agents have negligible water solubility and high toxicity. To solve these problems, for the first time, chitosan nanoparticles and Anionic Linear Globular Dendrimer (D) were synthesized for the treatment of Leishmania major (L. major).MethodChitosan and dendrimer nanoparticles were synthesized, and Amp and BA were loaded into the nanoparticles. The particles were then characterized using various methods and their efficacy was evaluated in vitro and in vivo environments (parasite burden was confirmed using pathological studies and real-time PCR methods).ResultThe results of docking showed that Amp and BA can be loaded into chitosan and dendrimer nanoparticles. The results of physically drug loading efficiency for AK (Amphotericin B-chitosan), BK (Betulinic acid-chitosan), AD (Amphotericin B-Dendrimer) and BD (Betulinic acid- Dendrimer) were 90, 93, 84 and 96 percent, respectively. The characterization results indicated that the drugs were loaded into nanoparticles physically. Moreover, the increased solubility rate for AD=478, BD=790, AK=80 and BK=300 folds. Furthermore, the results of the drug delivery system showed the slow controlled drug release pattern with cellular uptake of more than 90%. The treatment results showed a 100 percent decrease of toxicity for the all nanodrugs was observed in vivo and in vitro environments. Moreover, AK10 and BK20 mg/kg reduced parasite burden by 83 percent (P<0.001), while AD50 and BD40 mg/kg reduced it to a lesser extent compared to glucantime.ConclusionAll the synthesized nanodrugs were completely succeeded by 100% to recovery the L. major induced pathological effects in the infected footpad. Also, the results of present study were confirmed with real-time PCR and the results showed that AK and BK were succeeded in a large extent to the treatment of L. major infection (P<0.001), therefore AK and BK could be considered as proper alternatives of choices drugs.

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“…The nanoparticles were characterized using SEM, TEM, AFM, FTIR and H-NMR methods according to the previous study 34…”

Section: Methodsmentioning

confidence: 99%

Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of Leishmania major: real-time PCR assay plus

Mehrizi¹,

Khamesipour²,

Ardestani³

et al. 2019

IJN

Self Cite

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“…Several studies have explored the use of nano-delivery system in improving the therapeutic efficacy of different drug molecules in the treatment of diseases. Mehrizi et al (2018) carried out the synthesis of a novel nanosized chitosan-betulinic acid delivery system, against resistant Leishmania, with the first clinical observation of this parasite in the kidney. It was discovered that chitosan nanoparticles synthesized using phase separation; and drug loading by phase separation, improved the therapeutic dose of betulinic acid to 20 mg/kg.…”

Section: An Overview Of Nano-delivery Systemsmentioning

confidence: 99%

“…It was discovered that chitosan nanoparticles synthesized using phase separation; and drug loading by phase separation, improved the therapeutic dose of betulinic acid to 20 mg/kg. More so, the successful improvement in the use of the nanosystem loaded betulinic acid in the treatment of leishmania, displayed both in in vitro and in vivo efficacy (Mehrizi et al, 2018).…”

Section: An Overview Of Nano-delivery Systemsmentioning

confidence: 99%

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

Adekiya

Kondiah

Choonara

et al. 2020

Front. Bioeng. Biotechnol.

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Schistosomiasis is one of the major parasitic diseases and second most prevalent among the group of neglected diseases. The prevalence of schistosomiasis may be due to environmental and socioeconomic factors, as well as the unavailability of vaccines for schistosomiasis. To date, current treatment; mainly the drug praziquantel (PZQ), has not been effective in treating the early forms of schistosome species. The development of drug resistance has been documented in several regions globally, due to the overuse of PZQ, rate of parasitic mutation, poor treatment compliance, co-infection with different strains of schistosomes and the overall parasite load. Hence, exploring the schistosome tegument may be a potential focus for the design and development of targeted anti-schistosomal therapy, with higher bioavailability as molecular targets using nanotechnology. This review aims to provide a concise incursion on the use of various advance approaches to achieve targeted anti-schistosomal therapy, mainly through the use of nano-enabled drug delivery systems. It also assimilates the molecular structure and function of the schistosome tegument and highlights the potential molecular targets found on the tegument, for effective specific interaction with receptors for more efficacious anti-schistosomal therapy.

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“…In L. donovani , BA has been shown to induce apoptosis through DNA topoisomerase I and I inhibition [ 68 ]. More recently, BA was loaded into nanochitosan (K) to try to improve its therapeutic effects and decrease its adverse effects on a Leishmania major -infected BALB/c mice [ 69 ]. The synthesized K particles exhibited a size of 102 nm, whereas BA-nanochitosan (BK) had a size of 124 nm and a drug loading efficiency of 93%.…”

Section: Chitosan-based Drug Loaded Formulations For the Chemothermentioning

confidence: 99%

“…The drug uptake of 97% to 98% by cells, and a slow B release without toxicity were significant advantages. The activity of BK in the L. major BALB/c mice model at 20 mg/kg by intraperitoneal route for six weeks (alternative days) was shown to enhance the wound healing [ 69 ]. Considering these results, BK should be further studied to confirm its interest in the treatment of CL.…”

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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Novel Nanosized Chitosan-Betulinic Acid Against Resistant Leishmania Major and First Clinical Observation of such parasite in Kidney

Cited by 32 publications

References 49 publications

<p>Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of <em>Leishmania major</em>: real-time PCR assay plus</p>

<p>Comparative analysis between four model nanoformulations of amphotericin B-chitosan, amphotericin B-dendrimer, betulinic acid-chitosan and betulinic acid-dendrimer for treatment of <em>Leishmania major</em>: real-time PCR assay plus</p>

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

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

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