Advances in nanotechnology for improving the targeted delivery and activity of amphotericin B (2011-2023): a systematic review.

Amphotericin B (AmB) is a broad-spectrum therapeutic and effective drug, but it has serious side effects of toxicity and solubility. Therefore, reducing its toxicity should be considered in therapeutic applications. Nanotechnology has paved the way to improve drug delivery systems and reduce toxicity. The present study, for the first time, comprehensively reviews the studies from 2011 to 2023 on reducing the in vitro toxicity of AmB. The findings showed that loading AmB with micellar structures, nanostructured lipid carriers, liposomes, emulsions, poly lactide-co-glycolide acid, chitosan, dendrimers, and other polymeric nanoparticles increases the biocompatibility and efficacy of the drug and significantly reduces toxicity. In addition, modified carbon nanoparticles (including graphene, carbon nanotubes, and carbon dots) with positively charged amine groups, PEI, and other components showed favorable drug delivery properties. Uncoated and coated magnetic nanoparticles and silver NPs-AmB composites had less cytotoxicity and more antifungal activity than free AmB. Citrate-reduced GNPs and lipoic acid-functionalized GNPs were also effective nanocarriers to reduce AmB cytotoxicity and improve anti-leishmania efficacy. In addition, zinc oxide-NPs and PEGylated zinc oxide-NPs showed favorable antifungal activity and negligible toxicity. According to a review study, carbon-based nanoparticles, metal nanoparticles, and especially polymer nanoparticles caused some reduction in the toxicity and improved solubility of AmB in water. Overall, considering the discussed nanocarriers, further research on the application of nanotechnology as a cost-effective candidate to improve the efficiency and reduce the cytotoxicity of AmB is recommended.

Application of non-metal nanoparticles, as a novel approach, for improving the stability of blood products: 2011-2021.

Despite the importance of the proper quality of blood products for safe transfusion, conventional methods for preparation and their preservation, they lack significant stability. Non-metal nanoparticles with particular features may overcome these challenges. This review study for the first time provided a comprehensive vision of the interaction of non-metal nanoparticles with each blood product (red blood cells, platelets and plasma proteins). The findings of this review on the most effective nanoparticle for improving the stability of RBCs indicate that graphene quantum dots and nanodiamonds show compatibility with RBCs. For increasing the stability of platelet products, silica nanoparticles exhibited a suppressive impact on platelet aggregation. Pristine graphene also shows compatibility with platelets. For better stability of plasma products, graphene oxide was indicated to preserve free human serum albumin from thermal shocks at low ionic strength. For increased stability of Factor VIII, mesoporous silica nanoparticles with large pores exhibit the superb quality of recovered proteins. Furthermore, 3.2 nm quantum dots exhibited anticoagulant effects. As the best promising nanoparticles for immunoglobulin stability, graphene quantum dots showed compatibility with γ-globulins. Overall, this review recommends further research on the mentioned nanoparticles as the most potential candidates for enhancing the stability and storage of blood components.

Evaluation of the effects of nanoparticles on the therapeutic function of platelet: a review.

OBJECTIVES: Nanotechnology and nanoparticles are used in different applications in disease monitoring and therapy in contact with blood. Nanoparticles showed different effects on blood components and reduced or improved the function of therapeutic platelet during the storage time. This review study was performed to evaluate the impacts of various sizes and charges of nanoparticles on platelet function and storage time. The present review contains the literature between 2010 and 2020. The data have been used from different sites such as PubMed, Wiley, ScienceDirect and online electronic journals. KEY FINDINGS: From the literature survey, it has been demonstrated that among various properties, size and charge of nanoparticles were critical on the function of therapeutic platelet during the storage and inhibition of their aggregation. Overall, this study described that nanoparticles with smaller size and negative charge were more effective in increasing the survival time, inhibition of aggregation and improving the function of therapeutic platelet. SUMMARY: Based on the current review, it can be confirmed that nanoparticles such as dendrimer, Au, Ag and iron oxide nanoparticles with smaller size and negative charge have significant advantages for improving the efficacy of platelets during the storage chain and inhibition of their aggregation.

An overview on the investigation of nanomaterials' effect on plasma components: immunoglobulins and coagulation factor VIII, 2010-2020 review.

FVIII and immunoglobulins (Igs) are the most prominent plasma proteins, which play a vital role in plasma hemostasis. These proteins have been implemented frequently in protein therapy. Therefore, their maintenance, durability, and stability are highly essential. Herein, various approaches to improve protein functions have been investigated, such as using recombinant protein replacement. In comparison, advances in nanotechnology have provided adequate context to boost biomaterial utilization. In this regard, the applications of various nanoparticles such as polymeric nanomaterials (PEG and PLGA), metal nanoparticles, dendrimers, and lipid based nanomaterials (liposomes and lipid nanoparticles) in stability and the functional improvement of antibodies and coagulation factor VIII (FVIII) have been reviewed from 2010 to 2020. Reviewing related articles has shown that not only can nanomaterials adequately protect the structure of proteins, but have also improved proteins' functions in some cases. For example, the high rate of FVIII instability has been successfully enhanced by bio-PEGylation. Also, utilizing PEGylated liposomes, using the PEG-lip technique for coating nanostructures, leads to FIIIV half-life prolongation. Hence, PEGylation had most impact on the stability of FVIII. Likewise, PEG-coated liposome nano-carriers also presented such a good effect on stability improvements for FVIII due to their ability to tune the immune system by reducing FVIII immunogenicity. Similarly, Ig PEGylation and conjugation to magnetic nanoparticles resulted in increased half-life and better purification of Igs, respectively, without any loss in structural or functional features. Consequently, metal-organic frameworks and recent hybrid systems have been introduced as promising nanomaterials in biomedical applications. As far as we know, this is the first study in this field, which considers the applications of nanoparticles for improving the storage and stability of antibodies and coagulation FVIII.

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.

BACKGROUND: Amphotericin 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). METHOD: Chitosan 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). RESULT: The 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. CONCLUSION: All 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.

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

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.

Polybutylcyanoacrylate nanoparticles and drugs of the platinum family: last status.

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 µM) were estimated 64 ± 1 and 67 ± 0.5 %, respectively. These values at the highest concentration (p < 0.01) (160 µM) were measured 28 ± 0.7 and 31 ± 0.4 %. Additionally for carboplatinum and nanoparticles containing carboplatinum at the concentration (p < 0.01) (20 µM) amounts were estimated to be 80 ± 0.6 and 84 ± 0.6 %, while at the concentration (p < 0.01) (160 µM) 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.