Pegylation, a Successful Strategy to Address the Storage and Instability Problems of Blood Products: Review 2011-2021.

Conjugation of polyethylene glycol (PEGylation) to blood proteins and cells has emerged as a successful approach to address some of the issues attributed to the storage of blood products, including their short half-life and instability. In this regard, this review study aims to compare the influence of different PEGylation strategies on the quality of several blood products like red blood cells (RBCs), platelets, plasma proteins, i.e., albumin, coagulation factor VIII, and antibodies. The results indicated that conjugating succinimidyl carbonate methoxyPEG (SCmPEG) to platelets could improve blood transfusion safety by preventing these cells from being attached to low-load hidden bacteria in blood products. Moreover, coating of 20 kD succinimidyl valerate (SVA)-mPEG to RBCs was able to extend the half-life and stability of these cells during storage, as well as immune camouflage their surface antigens to prevent alloimmunisation. As regards albumin products, PEGylation improved the albumin stability, especially during sterilization, and there was a relationship between the molecular weight (MW) of PEG molecules and the biological half-life of the conjugate. Although coating antibodies with short-chain PEG molecules could enhance their stabilities, these modified proteins were cleared from the blood faster. Also, branched PEG molecules enhanced the retention and shielding of the fragmented and bispecific antibodies. Overall, the results of this literature review indicate that PEGylation can be considered a useful tool for enhancing the stability and storage of blood components.

Therapeutic Application of Nanoparticles in Hepatitis Diseases: A Narrative Review (2011-2021).

Hepatitis, an inflammation of the liver parenchyma, is a viral disease. Addressing the challenges of hepatitis is very important. Therefore, using nanoparticles (NPs) in solving the problems of hepatitis diagnosis and treatment can be considered a promising approach. To the best of our knowledge, there are few studies to review the most widely used and effective NPs in the field of hepatitis. A literature review was performed on the publications available on the subject matter from 2011 to 2021. The keywords in different combinations such as "hepatitis," "nanobiosensor," "nanoparticles," "drug delivery," "vaccination," "HBV," and "HCV" were searched in databases of PubMed and Scopus. The collected data were then analyzed. Our review study for introducing the widely used metallic, polymeric and carbon-based NPs with more promising effects in the field of hepatitis virus infection shows that the most effective metallic NPs were gold nanoparticles for designing detection sensors. Also, among polymeric NPs, chitosan NPs seem to be the best nanocarriers in drug delivery and vaccination for hepatitis and among carbon-based NPs, carbon dots had more promising effects for biosensing of hepatitis. According to the results, it is suggested that more studies could be conducted on these NPs for further studies on hepatitis as well as other viral infectious diseases.

A Review of the Use of Metallic Nanoparticles as a Novel Approach for Overcoming the Stability Challenges of Blood Products: A Narrative Review from 2011-2021.

PURPOSE: To obtain safe and qualified blood products (e.g., platelets, plasma, and red blood cells), various limitations such as limited shelf life (especially for platelets) and stability must be addressed. In this review study, the most commonly used metal nanomaterials (e.g., gold, silver, iron, and magnetic) reported in the literature from 2011 to 2021 were discussed owing to their unique properties, which provide exciting approaches to overcome these limitations and improve the stability, safety, and quality of blood products. Novelty: This study reviews for the first time the results of studies (from 2011 to 2021) that consider the effects of various metallic nanoparticles on the different blood products. RESULTS: The results of this review study showed that some metallic nanoparticles are effective in improving the stability of plasma proteins. For this purpose, modified Fe3O4 magnetic nanoparticles and citrate-AuNPs protect albumin products against stressful situations. Also, SiO2 microspheres and silicacoated magnetite nanoparticles are highly capable of improving IgG stability. ZnO nanoparticles also reduced thrombin production, and protein-coated GMNP nanoparticles prevented unwanted leakage of factor VIII through blood vessels. Furthermore, the stability and longevity of erythrocytes can be improved by AuNP nanoparticles and Zr-based organic nanoparticles. In addition, platelet storage time can be improved using PEGylated Au and functionalized iron oxide nanoparticles. SUGGESTION: According to the results of this study, it is suggested that further research should be conducted on metal nanoparticles as the most promising candidates to prepare metal nanoparticles with improved properties to increase the stability of various blood products.

An Overview of the Latest Applications of Platelet-Derived Microparticles and Nanoparticles in Medical Technology 2010-2020.

Today, Platelets and platelet-derived nanoparticles and microparticles have found many applications in nanomedical technology. The results of our review study show that no article has been published in this field to review the current status of applications of these platelet derivatives so far. Therefore, in the present study, our goal is to compare the applications of platelet derivatives and review their latest status between 2010 and 2020 to present the latest findings to researchers. A very interesting point about the role of platelet derivatives is the presence of molecules on their surface, which makes them capable of hiding from the immune system, reaching different target cells, and specifically attaching to different cell types. According to the results of this study, most of their applications include drug delivery, diagnosis of various diseases, and tissue engineering. However, their application in drug delivery is limited due to heterogeneity, large size, and the possibility of interference with cellular pathways in microparticles derived from other cells. On the other hand, platelet nanoparticles are more controllable and have been widely used for drug delivery in the treatment of cancer, atherosclerosis, thrombosis, infectious diseases, repair of damaged tissue, and photothermal therapy. The results of this study show that platelet nanoparticles are more controllable than platelet microparticles and have a higher potential for use in medicine.

Effects and treatment applications of polymeric nanoparticles on improving platelets' storage time: a review of the literature from 2010 to 2020.

Maintaining the quality of platelet products and increasing their storage time are priorities for treatment applications. The formation of platelet storage lesions that limit the storage period and preservation temperature, which can prepare a decent environment for bacterial growth, are the most important challenges that researchers are dealing with in platelet preservation. Nanotechnology is an emerging field of science that has introduced novel solutions to resolve these problems. Here, we reviewed the reported effects of polymeric nanoparticles-including chitosan, dendrimers, polyethylene glycol (PEG), and liposome-on platelets in articles from 2010 to 2020. As a result, we concluded that the presence of dendrimer nanoparticles with a smaller size, negative charge, low molecular weight, and low concentration along with PEGylation can increase the stability and survival of platelets during storage. In addition, PEGylation of platelets can also be a promising approach to improve the quality of platelet bags during storage.

A Review Study about the Effect of Chitosan Nanocarrier on Improving the Efficacy of Amphotericin B in the Treatment of Leishmania from 2010 to 2020.

In the present review study, the published articles from 2010-2020 that evaluated the effect of chitosan nanocarrier on the efficacy of amphotericin B (AmB) in the treatment of leishmaniasis, have been considered. Leishmania is a parasitic tropical disease in the world and is treated with AmB as one of the main therapeutic agents. However, the clinical application of AmB is limited due to its toxicity and insolubility issues. Using nanoparticles and, in particular, chitosan, nanocarrier seems a promising approach to overcome these problems. Therefore, various doses of AmB have been loaded in chitosan nanoparticles in different studies and the results of these studies demonstrated that by increasing the drug loading efficiency and decreasing the toxicity, the potency of the nanoformulation to inhibit and to kill the parasite is increased. In this regard, the results of a study performed in 2018, demonstrated that chitosan nanoparticles with the higher dose of drug loading were the most effective formulation to inhibit and kill the parasite. Thus, chitosan nanocarrier can consider as an appropriate candidate in the future to inhibit and kill the Leishmania parasite without causing side effects.

Novel nano-sized chitosan amphotericin B formulation with considerable improvement against Leishmania 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.

Reduction toxicity of Amphotericin B through loading into a novel nanoformulation of anionic linear globular dendrimer for improve treatment of leishmania major.

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.

Effect of gold nanoparticles on properties of nanoliposomal hydroxyurea: an in vitro study.

New hopes in cancer treatment have been emerged using functional nanoparticles. In this work, we tried to synthesize gold nanoparticles and gold nanoparticles conjugated with DNA extracted from human breast cancer cells. After synthesizing, gold nanoparticles were mixed with nanoliposomal hydroxyurea and corresponding compounds were formed. They were described by UV-Visible spectrophotometry and Zeta sizer. Amount of drug loading into liposomes was determined by spectrophotometry and cytotoxicity effect on MCF-7 cells was measure by MTT assay. Drug loading was determined to be 70 %. Size, size distribution and Zeta potential of particles were 473 nm, 0.46 and -21 mV for control nanoliposomal ones and 351 nm, 0.38 and -25 mV for nanoliposomal particles containing hydroxyurea. This was 29 nm, 0.23 and -30 mV for gold nanoparticles and 502 nm, 0.41 and -38 mV for nanoliposomes containing drug loaded by gold nanoparticles conjugated with DNA. It was found that nano conjugated complex in concentrations less than 20 µM of hydroxyurea can improve efficiency compared with liposomal drug. In maximum concentration of drug (2,500 µM), cytotoxicity was equal to 95 %. In minimum concentration of drug (5 µM), cytotoxicity of liposomal drug and conjugated complex were 70 and 81 %, respectively which probably comes from increased drug entry into cells due to the presence of gold nanoparticles. Free drug resulted in toxicity of 32 % in 5 µM and 88 % in 2,500 µM. Results demonstrated higher drug efficiency in nanoparticle form compared with free form which can be used in in vivo studies.