Regarding the antiparasitic effects of Betulinic acid (B) against Leishmaniasis, it was loaded into nanochitosan (K) for the first time in order to improve its therapeutic effects and decrease its side effects for the treatment of Leishmania major-infected Balb/c mice. Improvement the therapeutic efficacy of Bas an anti-leishmania agent through increasing the effective dose was achieved by using a novel solvent and phase separation method for K synthesis. The synthesized K with the size of 102 nm and Betulinic acid-nanochitosan (BK) with the size of 124 nm and drug loading efficiency of 93%, cellular uptake of 97.5% with the slow drug release pattern was prepared. To increase the therapeutic dose, a modified 10% acetic acid solvent was used. The in vitro and in vivo results showed that the nanodrug of BK was non toxic by 100% and BK20 mg/kg could completely performed the wound healing and inhibit the parasite in a large extent (P ˂ 0.001) compared to other groups. Therefore, BK could be considered as an alternative regimen for treatment of L. major.

Aim: Improvement in the treatment of Leishmania major's pathological effects through increasing the dose of amphotericin B loaded into nanochitosan. Materials & methods: The phase separation method was used for nanochitosan synthesis and amphotericin loading. Also a novel solvent was designed and the nanodrug efficacy was evaluated in vitro and in vivo (pathology) environments. Results: The drug loading efficiency of 90%, along with slow drug-release with cellular uptake of 98.6% was achieved. The novel solvent was composed of 10% acetic acid, and it was succeeded to dissolve AK10 mg/kg. Also, AK10 mg/kg had no side effects in in vitro and in vivo environments. In addition, the complete wound healing and parasite inhibition were achieved by using AK10 mg/kg in terms of improvement the treatment indicators. Conclusion: Increasing the therapeutic dose of AK to 10 mg/kg caused the successful treatment of L. major's pathological effects in in vitro and in vivo environments.

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.

Amphotericin B (A) as an antileishmanial drug has limited clinical application owing to severe side-effects and low-water solubility. This is the first study reported using Anionic Linear Globular Dendrimer (ALGD) as A carrier for the increase of A solubility rate, decrease its toxicity, and improve its therapeutic effects. ALGD was synthesized and A was loaded into nanoparticles for the first time with the drug-loading efficiency of 82%. Drug loading was confirmed using characterization methods. The drug solubility rate was increased by 478-folds. The results of the study showed that the A toxicity was significantly decreased by 95% in vitro and in vivo environments, which was confirmed by pathology findings and enzymatic evaluation. Furthermore, the nanodrug caused that mortality rate was reached to zero. Moreover, the nanodrug was as potent as the free drug and glucantime (GUL) in reducing the parasite burden and parasite number. These findings indicated the potency of ALGD to decrease the drug side-effects, increase the drug solubility rate, and improve the drug efficacy. Moreover, the nanoformulation was a non-toxic and cost-effective formulation. The conformity between in vitro and in vivo results suggested that the A-loaded ALGD could be considered as a promising candidate in reducing the side-effects of A in leishmaniasis treatment.

Cisplatinum and carboplatinum drugs from platinum-containing family are anti-cancer drugs. Using these drugs causes side effects. Targeted and selective prescription decreases side effects of the drugs. This can be achieved using nanotechnology. In this study, cisplatinum and carboplatinum drugs were loaded on polybutylcyanoacrylate nanoparticles using emulsion polymerization method. To determine amount of loaded drug onto nanoparticle, spectrophotometry method was used. Evaluation of cytotoxicity of such nanoparticles was performed on MCF-7 cell line using MTT assay. Loading percentage of cisplatinum and carboplatinum drugs on nanoparticles were estimated 4 and 6 %, respectively. Cytotoxicity survival rate for cisplatinum and nanoparticle containing cisplatinum at the lowest concentration (p \ 0.01) (20 lM) were estimated 64 ± 1 and 67 ± 0.5 %, respectively. These values at the highest concentration (p \ 0.01) (160 lM) were measured 28 ± 0.7 and 31 ± 0.4 %. Additionally for carboplatinum and nanoparticles containing carboplatinum at the concentration (p \ 0.01) (20 lM) amounts were estimated to be 80 ± 0.6 and 84 ± 0.6 %, while at the concentration (p \ 0.01) (160 lM) were identified to be 44 ± 0.5 and 51 ± 0.2 %, respectively. Probably, due to low level of loading, cytotoxicity of both drugs at nano particle status was decreased in comparison with their standard form.