Surfactant Proteins A/D-CD14 on Alveolar Macrophages Is a Common Pathway Associated With Phagocytosis of Nanomaterials and Cytokine Production.

Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production, and to determine whether a common pathway for phagocytosis of ENMs with different properties exists. For these purposes, four ENMs, MWCNT-7, TiO2, SiO2, and fullerene C60, with different shapes, sizes, chemical compositions, and surface reactivities, were chosen for this study. Short-term pulmonary exposure to MWCNT-7, TiO2, SiO2, and C60 induced inflammation in the rat lung, and most of the administered ENMs were phagocytosed by alveolar macrophages. The ENMs were phagocytosed by isolated primary alveolar macrophages (PAMs) in vitro, and phagocytosis was enhanced by rat bronchioalveolar lavage fluid (BALF), suggesting that proteins in the BALF were associated with phagocytosis. Analysis of proteins bound to the 4 ENMs by LC/MS indicated that surfactant-associated proteins A and D (SP-A, SP-D) were common binding proteins for all the 4 ENMs. Both BALF and SP-A, but not SP-D, enhanced TNF-α production by MWCNT-7 treated PAMs; BALF, SP-A, and SP-D increased IL-1ß production in TiO2 and SiO2 treated PAMs; and BALF, SP-A, and SP-D enhanced IL-6 production in C60 treated PAMs. Knockdown of CD14, a receptor for SP-A/D, significantly reduced phagocytosis of ENMs and SP-A-enhanced cytokine production by PAMs. These results indicate that SP-A/D can opsonize all the test ENMs and enhance phagocytosis of the ENMs by alveolar macrophages through CD14, suggesting that SP-A/D-CD14 is a common pathway mediating phagocytosis of ENMs. Cytokine production induced by ENMs, however, is dependent on the type of ENM that is phagocytosed. Our results demonstrate a dual role for surfactant proteins as opsonins for both microbes and for inhaled dusts and fibers, including ENMs, allowing macrophages to recognize and remove the vast majority of these particles, thereby, greatly lessening their toxicity in the lung.

Evaluation of the C60 biodistribution in mice in a micellar ExtraOx form and in an oil solution.

The article is devoted to the study of the pharmacokinetics of fullerene C60 in oil and micellar forms, analysis of its content in blood, liver, lungs, kidneys, heart, brain, adrenal glands, thymus, testicles, and spleen. The highest accumulation of C60 was found in the liver and adrenal glands. As a result of the studies carried out, it was shown that the bioavailability of C60 in the micellar form is higher than that in an oil solution.

FULLEROL alleviates myocardial ischemia-reperfusion injury by reducing inflammation and oxidative stress in cardiomyocytes via activating the Nrf2/HO-1 signaling pathway.

OBJECTIVE: Myocardial ischemia-reperfusion injury (MIRI) is myocardial tissue injury caused by blood supply returning to myocardial tissue after ischemia or hypoxia. The purpose of this study was to investigate the protective effect of FULLEROL on myocardial tissue in MIRI rats and its mechanism. MATERIALS AND METHODS: We use rats and ligate their left anterior descending coronary artery to make a MIRI model, and we also subcutaneously injected some MIRI rats with FULLEROL daily for two weeks before modeling. We determined the effects of model building and the therapeutic effect of FULLEROL on MIRI by detecting the changes of myocardial tissue morphology, myocardial injury markers and cardiac function in rats. In addition, we detected the expression changes of inflammatory factors and antioxidative molecules in rat myocardial tissue and serum to determine the effect of FULLEROL on inflammation and oxidative stress in myocardial tissue. Finally, we detected the activity of the Nrf2/HO-1 signaling pathway in rat cardiomyocytes to determine the mechanism of action of FULLEROL. RESULTS: The structure of myocardial tissue in MIRI rats was remarkably damaged, and the range of myocardial infarction was increased. In addition, the concentrations of creatine kinase and lactate dehydrogenase were increased, and the heart function was reduced, while FULLEROL could reverse these conditions. In addition, FULLEROL was found to reduce the concentration of the inflammatory factors in rat myocardial tissue and serum, and to increase the expression of antioxidative molecules in myocardial tissue. The Nrf2/HO-1 signaling pathway was found to be related to MIRI and FULLEROL could increase the activity of the Nrf2/HO-1 signaling pathway in cardiomyocytes. CONCLUSIONS: FULLEROL can alleviate MIRI by promoting the activity of the Nrf2/HO-1 signaling pathway to reduce the expression of inflammatory factors in rats and increase the antioxidative capacity of cardiomyocytes.

Characterization and Cytotoxicity of Polyprenol Lipid and Vitamin E-TPGS Hybrid Nanoparticles for Betulinic Acid and Low-Substituted Hydroxyl Fullerenol in MHCC97H and L02 Cells.

BACKGROUND: This study demonstrated an innovative formulation including the polyprenol (GBP) lipid and vitamin E-TPGS hybrid nanoparticles (NPs) which was aimed to control the transfer of betulinic acid (BA) and low-substituted hydroxyl fullerenol (C60(OH)n). Additionally, it developed BA-C60(OH)n-GBP-TPGS-NPs delivery system and researched the anti-hepatocellular carcinoma (HCC) effects. MATERIALS AND METHODS: The NPs were prepared by nanoprecipitation with ultrasonic-assisted emulsification (UAE) method. It was characterized by scanning electronic microscopy (SEM), transmission electron microscopy (TEM), FTIR spectrum, size distribution and zeta potential. Physical and chemical properties were evaluated through measurement of drug release, stability studies, drug loading efficiency (DE) and encapsulation efficiency (EE). Biological activities were evaluated through measurement of MTT assay, lactate dehydrogenase leakage assay (LDH), cell proliferation assays, cell apoptosis analysis, comet assay, wound healing assay, cell invasion and Western blot analysis. RESULTS AND CONCLUSIONS: The NPs exhibited clear distribution characteristics, improved solubility and stability. BA and C60(OH)n for the NPs displayed a biphasic release pattern with sustained drug release properties. The mixture of C60(OH)n with different hydroxyl groups may have a certain effect on the stability of the NPs system itself. The NPs could effectively inhibit MHCC97H cell proliferation, migration and invasion in vitro. Combined use of C60(OH)n and BA in GBP lipids may improve the inhibit effect of C60(OH)n or BA against HCC cells and reduce cytotoxicity and genotoxicity of C60(OH)n for normal cells. We concluded that one of the important mechanisms of BA-C60(OH)n-GBP-TPGS-NPs inhibiting MHCC97H cells is achieved by up-regulating the expression of Caspase-3, Caspase-8 and Caspase-9.

Water-Soluble C60 Protects Against Bleomycin-Induced Pulmonary Fibrosis in Mice.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia. And, oxidation/antioxidant imbalance plays an important role in the progress of IPF. Fullerene is considered to be a novel "structural" antioxidant. This study aimed to explore if water-soluble C60 (C60(OH)22) can exhibit antifibrotic activity in its antioxidant role. METHODS: Healthy C57BL/6J mice were randomly grouped and induced pulmonary fibrosis by intratracheal injection of bleomycin. RESULTS: The survival rate of mice was observed and found that 10mg/kg was the optimal dose of water-soluble C60 for pulmonary fibrosis. We observed that water-soluble C60 can alleviate the severity of pulmonary fibrosis by observing the chest computed tomography, pulmonary pathology, and content of collagen, alpha smooth muscle actin and fibronectin in lung. Compared with bleomycin group, ROS, the content of TNF-α in BALF, and the number of fibroblasts was significantly decreased and the number of type Ⅱ alveolar epithelial cells was increased after treatment with C60. CONCLUSION: Therefore, thanks to its powerful antioxidant action, water-soluble C60 can reduce the severity of pulmonary fibrosis induced by bleomycin in mice.

Effects of fullerene C60 supplementation on gut microbiota and glucose and lipid homeostasis in rats.

The effects of twelve weeks of supplementation with fullerene C60 olive/coconut oil solution on a broad spectrum of parameters in rats were examined. The tissue bioaccumulation of C60 was shown to be tissue-specific, with the liver, heart, and adrenal glands being the organs of the greatest, and the kidney, brain, and spleen being the organs of the smallest accumulation. C60 did not change aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase serum activities level, nor the damage of liver cells DNA. There were no effects of fullerene on prooxidant-antioxidant balance in the liver, kidney, spleen, heart, and brain, nor any visible harmful effects on the liver, heart, aorta, spleen, kidney, and small intestine histology. Fullerene changed the gut microbiota structure towards the bacteria that ameliorate lipid homeostasis, causing a serum triglycerides concentration decrease. However, C60 significantly increased the insulin resistance, serum ascorbate oxidation, and brain malondialdehyde and advanced oxidation protein products level. The deteriorative effects of C60 on the brain and serum could be attributed to the specific physicochemical composition of these tissues, potentiating the C60 aggregation or biotransformation as the key element of its pro-oxidative action.

Nanoparticles in dermatologic surgery.

Nanotechnology is an emerging branch of science that involves the engineering of functional systems on the nanoscale (1-100 nm). Nanotechnology has been used in biomedical and therapeutic agents with the aim of providing novel treatment solutions where small molecule size may be beneficial for modulation of biologic function. Recent investigation in nanomedicine has become increasingly important to cutaneous pathophysiology, such as functional designs directed towards skin cancers and wound healing. This review outlines the application of nanoparticles relevant to dermatologic surgery.

[Preparation and Evaluation of Fullerene Based Nanomedicine].

Fullerenes, large spherical molecules composed solely of carbon atoms, have gathered much attention for practical applications that take advantage of their unique spherical structure, physical properties, and biological activities. For example, fullerene C60 can function as a photosensitizer, an antioxidant, a bioimaging agent, and as a gene or drug carrier. However, the practical use of C60 for these potential biomedical applications has been hampered by the fact that it is only sparingly soluble in water. In this review, we focus on the development of hydrophilic C60 nanoparticles, the surface of which is covered by cyclodextrin (CD), and then evaluate its biological activities. C60/CD nanoparticles were stable under physiological conditions, and even under much harsher conditions. The nanoparticles generate reactive oxygen species (ROS) under visible light irradiation. Efficient photodynamic therapy against tumor growth was achieved by the intravenous injection of C60/CD nanoparticles to tumor bearing mice, followed by photoirradiation. In addition, C60(OH)10, which is regarded as a potential candidate for use in scavenging ROS, was also prepared in the form of water soluble nanoparticles. C60(OH)10/CD nanoparticles protect the liver from injury by the suppression of oxidative stress occurring in the mitochondria, for example, by scavenging ROS such as superoxide anion radicals (O2・-), nitric oxide (NO) and peroxynitrite (ONOO-), which act as critical mediators in liver injuries. C60-based nanoparticles represent a potentially promising material for use in the treatment of cancer and oxidative stress-related diseases, and are promising as well in terms of extensive biological applications.

Nanocarbons for Biology and Medicine: Sensing, Imaging, and Drug Delivery.

Nanocarbons with different dimensions (e.g., 0D fullerenes and carbon nanodots, 1D carbon nanotubes and graphene nanoribbons, 2D graphene and graphene oxides, and 3D nanodiamonds) have attracted enormous interest for applications ranging from electronics, optoelectronics, and photovoltaics to sensing, bioimaging, and therapeutics due to their unique physical and chemical properties. Among them, nanocarbon-based theranostics (i.e., therapeutics and diagnostics) is one of the most intensively studied applications, as these nanocarbon materials serve as excellent biosensors, versatile drug/gene carriers for specific targeting in vivo, effective photothermal nanoagents for cancer therapy, and promising fluorescent nanolabels for cell and tissue imaging. This review provides a systematic overview of the latest theranostic applications of nanocarbon materials with a comprehensive comparison of the characteristics of different nanocarbon materials and their influences on theranostic applications. We first introduce the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties. Theranostic applications are described separately for both in vitro and in vivo systems by highlighting the protocols and the studied biosystems, followed by the toxicity and biodegradability implications. Finally, this review outlines the design considerations for nanocarbon materials as the key unifying themes that will serve as a foundational first principle for researchers to study, investigate, and generate effective, biocompatible, and nontoxic nanocarbon materials-based models for cancer theranostics applications. Finally, we summarize the review with an outlook on the challenges and novel theranostic protocols using nanocarbon materials for hard-to-treat cancers and other diseases. This review intends to present a comprehensive guideline for researchers in nanotechnology and biomedicine on the selection strategy of nanocarbon materials according to their specific requirements.

Fullerene-based delivery systems.

With the development of new drugs, there have been many attempts to explore innovative delivery routes. Targeted delivery systems are a desired solution designed to overcome the deficiency of routine methods. To transform this idea into reality, a wide range of nanoparticles has been proposed and studied. These nanoparticles should interact well with biological environments and pass through cell membranes to deliver therapeutic molecules. One of the pioneer classes of carbon-based nanoparticles for targeted delivery is the fullerenes. Fullerenes have a unique structure and possess suitable properties for interaction with the cellular environment. This short review concentrates on newly developed fullerene derivatives and their potential as advanced delivery systems for pharmaceutical applications.

Disposition of fullerene C60 in rats following intratracheal or intravenous administration.

Fullerene C60 is used in a variety of industrial and consumer capacities. As part of a comprehensive evaluation of the toxicity of fullerene C60 by the National Toxicology Program, the disposition following intratracheal (IT) instillation and intravenous (IV) administration of 1 or 5 mg/kg b.wt. fullerene C60 was investigated in male Fischer 344 rats. Following IT instillation, fullerene C60 was detected in the lung as early as 0.5 h post-exposure with minimal clearance over the 168 h period; the concentration increased ≥20-fold with a 5-fold increase in the dose. Fullerene C60 was not detected in extrapulmonary tissues. Following IV administration, fullerene C60 was rapidly eliminated from the blood and was undetectable after 0.5 h post-administration. The highest tissue concentrations of fullerene C60 occurred in the liver, followed by the spleen, lung and kidney. Fullerene C60 was cleared slowly from the kidney and the lung with estimated half-lives of 24 and 139 h, respectively. The liver concentration of fullerene C60 did not change much with time; over 90% of the fullerene C60 remained there over the study duration up to 168 h. Fullerene C60 was also not detected in urine or feces. These data support the hypothesis that fullerene C60 accumulates in the body and therefore has the potential to induce detrimental health effects following exposure.

Amino acid modified [70] fullerene derivatives with high radical scavenging activity as promising bodyguards for chemotherapy protection.

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients' organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and ß-alanine were separately employed to chemically modify C70 fullerene, and L-lysine derivative of fullerene (C70-Lys) exhibits superior radical scavenging activity to ß-alanine derivative of C70 (C70-Ala). As expected, C70-Lys show much better protective effect than C70-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.

Fullerenol C60(OH)36 at relatively high concentrations impairs hippocampal theta oscillations (in vivo and in vitro) and triggers epilepsy (in vitro) - A dose response study.

Since the first identification of fullerenes (C60) and their synthesis in 1985, those compounds have been extensively studied in the biomedical field. In particular, their water-soluble derivatives, fullerenols (C60(OH)n, n = 2-48), have recently been the subject of numerous investigations concerning their antioxidant and prooxidant properties in biological systems. A small fraction of that research has focused on the possible use of C60 and C60(OH)n in neuroscience and the therapy of pathologies such as dementia, amyloid-ß (Aß) formation, and Parkinson's disease. However, only a few studies have focused on their direct effects on neuronal network viability and excitability, especially with the use of electrophysiological and electrochemical approaches. Therefore, we addressed the issue of the direct effect of hydroxylated fullerene nanoparticles C60(OH)36 on local field potentials at the hippocampal formation (HPC) level. With the use of in vitro hippocampal formation slices as a stable model of inducing theta oscillations, and an in vivo model of an anesthetized rat, herein we provide the first convergent electropharmacological evidence that C60(OH)36 at relatively high concentrations (60 µM and 80 µM in vitro; 0.2 µg/µl in vivo) is capable of attenuating the amplitude, power, and frequency of theta oscillations in the HPC neuronal network. At the same time, lower concentrations did not induce any apparent changes. Theta band oscillations constitute a key physiological phenotypic property, which served here as a sensitive assay enabling the study of neural network excitability. Moreover, we report that C60(OH)36 at the concentrations of 60 µM and 80 µM is capable of producing epilepsy in the HPC in vitro, which suggests that C60(OH)n, when applied at higher doses, may have a deleterious effect on the functioning of neuronal networks.

Inhalable gadofullerenol/[70] fullerenol as high-efficiency ROS scavengers for pulmonary fibrosis therapy.

Pulmonary fibrosis has become a fatal disease for its high incidence and few effective drugs available in clinic. In this study, gadofullerenol (GF-OH) and [70] fullerenol (C70-OH) nanoparticles (NPs) prepared by a one-pot reaction were designed as nanomedicines to treat this fatal disease. It was revealed that the inhalation of gadofullerenols and [70] fullerenols substantially alleviates the collagen deposition induced by acute lung injury. Based on detailed studies of oxidative stress parameters and transforming growth factor-ß1 (TGF-ß1), we demonstrated they owned the antioxidant and anti-inflammatory functions for the modulation of ROS-mediated inflammation process. Thus the therapeutic effect may be associated with synergistic mechanism of scavenging free radicals and indirectly modulating TGF-ß1 expression. Moreover, GF-OH NPs were observed to show the superiority to C70-OH NPs both in vitro and in vivo due to the structural distinction. These results suggest the inhalable fullerenols are highly potential for clinical therapy of pulmonary fibrosis.

Evaluation of the structure-activity relationship of carbon nanomaterials as antioxidants.

AIM: To develop the potential application of carbon nanomaterials as antioxidants calls for better understanding of how the specific structure affects their antioxidant activity. MATERIALS & METHODS: Several typical carbon nanomaterials, including graphene quantum dots and fullerene derivatives were characterized and their radical scavenging activities were evaluated; in addition, the in vitro and in vivo radioprotection experiments were performed. RESULTS: These carbon nanomaterials can efficiently scavenge free radicals in a structure-dependent manner. In vitro assays demonstrate that administration of these carbon nanomaterials markedly increases the surviving fraction of cells exposed to ionizing radiation. Moreover, in vivo experiments confirm that their administration can also increase the survival rates of mice exposed to radiation. CONCLUSION: All results confirm that large, buckyball-shaped fullerenes show the strongest antioxidant properties and the best radioprotective efficiency. Our work will be useful in guiding the design and optimization of nanomaterials for potential antioxidant and radioprotection bio-applications.

Pharmacokinetics and Toxicology of the Neuroprotective e,e,e-Methanofullerene(60)-63-tris Malonic Acid [C3] in Mice and Primates.

BACKGROUND AND OBJECTIVES: Fullerene-based compounds are a novel class of molecules being developed for a variety of biomedical applications, with nearly 1000 publications in this area in the last 4 years alone. One such compound, the e,e,e-methanofullerene(60)-63-tris malonic acid (designated C3), is a potent catalytic superoxide dismutase mimetic which has shown neuroprotective efficacy in a number of animal models of neurologic disease, including Parkinsonian Macaca fascicularis monkeys. The aim of this study was to characterize its toxicity and pharmacokinetics in mice and monkeys. METHODS: To assess pharmacokinetics in mice, we synthesized and administered 14C-C3 to mice using various routes of delivery, including orally. To assess potential toxicity in primates, serial blood studies and electrocardiograms (ECGs) were obtained from monkeys treated with C3 (3 or 7 mg/kg/day) for 2  months. RESULTS AND CONCLUSIONS: The plasma half-life of C3 was 8.2 ± 0.2 h, and there was wide tissue distribution, including uptake into brain. The compound was cleared by both hepatic and renal excretion. C3 was quite stable, with minimal metabolism of the compound even after 7 days of treatment. The LD50 in mice was 80 mg/kg for a single intraperitoneal injection, and was > 30 mg/kg/day for sustained administration; therapeutic doses are 1-5 mg/kg/day. For primates, no evidence of renal, hepatic, electrolyte, or hematologic abnormalities were noted, and serial ECGs demonstrated no alteration in cardiac electrical activity. Thus, doses of C3 that have therapeutic efficacy appear to be well tolerated after 2 years (mice) or 2 months (non-human primates) of treatment.

RF-assisted gadofullerene nanoparticles induces rapid tumor vascular disruption by down-expression of tumor vascular endothelial cadherin.

The tumor vasculature with unique characteristics offers an attractive target for anti-cancer therapy. Herein, we put forward a novel antitumor therapeutic mechanism based on the gadofullerene nanocrystals (GFNCs), the agent we have previously shown to efficiently disrupt tumor vasculature by size-expansion with assistance of radiofrequency (RF). However, the tumor vascular disrupting mechanism of RF-assisted GFNCs treatment was not further studied. In the present work, a rapid tumor blood flow shutdown has been observed by the vascular perfusion imaging in vivo and vascular damages were evident 6 h after the RF-assisted GFNCs treatment. Importantly, a significant down-expression of tumor vascular endothelial cadherin (VE-cadherin) treated by RF-assisted GFNCs was further investigated, which caused vascular collapse, blood flow shut-down and subsequent tumor hemorrhagic necrosis. These findings set forth a systematic mechanism on the superior anti-tumor efficiency by RF-assisted GFNCs treatment.

Small size fullerenol nanoparticles inhibit thrombosis and blood coagulation through inhibiting activities of thrombin and FXa.

Thrombus is one of main causes of death in the world and also a vital trouble of biomaterials application in vivo. Recently, effect of fullerenol nanomaterials on anticoagulation was found in our research through extension of bleeding times in treated Sprague-Dawley rats via intravenous injection. Inhibiting of fullerenols on thrombosis was ascertained further by thromboembolism model. Effects of fullerenols on intrinsic and extrinsic pathway were distinct in prolonging activated partial thromboplastin time and prothrombin time, which supported that fullerenols induced defects in both pathways. Inhibited activities of activated coagulation factor X (FXa) and thrombin were verified by experiments in vitro and AutoDock Vina. The results suggest that fullerenols depending on small size and certainly surface property occupied the active domain of FXa and thrombin to block their activity; further, thrombosis was inhibited. This putative mechanism offers an insight into how fullerenol NPs were utilized further in biomedical applications.

Fullerene C60 nanoparticles ameliorated cyclophosphamide-induced acute hepatotoxicity in rats.

Cyclophosphamide (CP), a chemotherapeutic agent, induces hepatotoxicity as one of its side effects. Therefore, the aim of the present study is to investigate the potential hepatoprotective effects of fullerene C60 nanoparticles (C60) against the high toxic dose of CP. Twenty five albino rats were randomly assigned to 5 groups (n=5 per group). Group 1 served as a control. Group 2 received 200mg/kg of CP once intraperitoneally, while group 3 treated with the same CP dose plus C60 (4mgkg, orally) daily for 10days. Group 4 exposed CP and ZnCl2 (4mgkg, orally) daily for 10days. Group 5 exposed to CP and co-treated with C60 and ZnCl2. One day after last treatment, blood and livers were collected for hematological, biochemical and histopathological investigations. C60 normalized significantly RBCs, HB, PCV, WBCs and platelets numbers compared to CP-exposed rats. Moreover, liver enzymes namely ALT, AST and ALP revealed that CP elevated their levels and C60 significantly (p<0.05) reduced them to basal levels. The level of oxidative stress marker namely, MDA was elevated upon CP exposure and normalized by C60 treatment. In addition, antioxidant systems e.g. GSH, CAT and SOD were depleted from liver tissue due to CP toxicity these were recovered by C60 administration. The hepatoprotective effects of C60 on tested parameters were comparable with ZnCl2 and neither additive nor synergistic effect was observed. Histopathogically, severe liver degeneration was recorded after CP treatment, however, only mild changes were observed after C60 administration. Our data suggest that C60 improves both blood and hepatic parameters altered by cyclophosphamide-induced toxicities. The current study is of clinical relevance particularly, application of C60 as a monotherapy or in combination to ameliorate the CP side effects in cancer-treated patients.

Recent advances in nanocarrier-loaded gels: Which drug delivery technologies against which diseases?

The combination of pharmaceutical technologies can be a wise choice for developing innovative therapeutic strategies. The association of nanocarriers and gels provides new therapeutic possibilities due to the combined properties of the two technologies. Gels support the nanocarriers, localize their administration to the target tissue, and sustain their release. In addition to the properties afforded by the gel, nanocarriers can provide additional drug sustained release or different pharmacokinetic and biodistribution profiles than those from nanocarriers administered by the conventional route to improve the drug therapeutic index. This review focuses on recent (over the last ten years) in vivo data showing the advances and advantages of using nanocarrier-loaded gels. Liposomes, micelles, liquid and solid lipid nanocapsules, polymeric nanoparticles, dendrimers, and fullerenes are all nanotechnologies which have been recently assessed for medical applications, such as cancer therapy, the treatment of cutaneous and infectious diseases, anesthesia, the administration of antidepressants, and the treatment of unexpected diseases, such as alopecia.