Cyclodextrin Functionalized Graphene Nanosheets for Targeted Delivery of Doxorubicin

A multifunctional nanocarrier based on cystamine (Cys) and β-cyclodextrin (β-CD) modified graphene oxide (GO) was designed for targeted delivery of Doxorubicin (DOX). The obtained CD-Cys-GO nanosheet was characterized by thermogravimetric analysis, Fourier transform infrared spectroscopy, Raman  spectroscopy, Atomic force microscopy and Field emission scanning electron microscopy, which confirmed that Cys and CD had been effectively functionalized on the surface of GO. DOX loading and delivery were also examined and the results suggested that multi-functionalized GO is an efficient nanocarrier for targeted delivery and controlled release of anticancer drug for biomedical applications. Introduction: Graphene oxide (GO) based drug carriers have been introduced as an important topic of research at the interface of nanotechnology and biomedicine due to their high specific surface area, enriched oxygen-containing groups, low cost and scalable production, excellent biocompatibility, and physiological stability. Cyclodextrin (CD) is a cyclic oligomer which its biological nature makes it attractive in pharmaceutical field. Moreover, the hydrophobic cavity of CD can selectively bind various organic, inorganic and biological molecules to form supramolecular complexes without structural changes. Methods and Results: In this research, GO nanosheet was synthesized according to Hummer’s method and then was functionalized by Cys in order to design a targeted and controlled drug delivery system. In the next step, β-CD was attached to free amine groups of attached Cys moieties on GO surface. DOX was used as a model drug to assess the drug-loading and releasing properties and the effect of pH was examined. The synthesized graphene-based nanomaterials were structurally and morphologically characterized with FT-IR, CHN, Raman, TGA, XRD and FE-SEM techniques. In addition, the CD-Cys-GO exhibited remarkably higher loading capacity for DOX than Cys-GO and GO. The release of drug was pH-sensitive which would control the release in acidic cytoplasm of cancer cells and can be due to the existence of disulfide bonds in the structure of this nanocarrier. Conclusions: In summary, a unique CD-Cys-GO system has been developed. The versatile system combines the advantages of graphene, Cys and CD that provides multifunctional and inter-reversible anchor sites. The hybrid is found to possess a high drug-loading capacity and strong targeting effect

Effect of PEGylation on assembly morphology and cellular uptake of poly ethyleneimine-cholesterol conjugates for delivery of sorafenib tosylate in hepatocellular carcinoma

Introduction: Sorafenib (SFB) is an FDA-approved chemotherapeutic agent with a high partition coefficient (log P = 4.34) for monotherapy of hepatocellular carcinoma (HCC). The oral bioavailability is low and variable, so it was aimed to study the application of the polymeric nanoassembly of cholesterol conjugates of branched polyethyleneimine (PEI) for micellar solubilization of SFB and to investigate the impact of the polymer PEGylation on the physicochemical and cellular characteristics of the lipopolymeric dispersions. Methods: Successful synthesis of cholesterol-PEI lipopolymers, either native or PEGylated, was confirmed by FTIR, 1H-NMR, pyrene assay methods. The nanoassemblies were also characterized in terms of morphology, particle size distribution and zeta-potential by TEM and dynamic light scattering (DLS). The SFB loading was optimized using general factorial design. Finally, the effect of particle characteristics on cellular uptake and specific cytotoxicity was investigated by flow cytometry and MTT assay in HepG2 cells. Results: Transmission electron microscopy (TEM) showed that PEGylation of the lipopolymers reduces the size and changes the morphology of the nanoassembly from rod-like to spherical shape. However, PEGylation of the lipopolymer increased critical micelle concentration (CMC) and reduced the drug loading. Moreover, the particle shape changes from large rods to small spheres promoted the cellular uptake and SFB-related cytotoxicity. Conclusion: The combinatory effects of enhanced cellular uptake and reduced general cytotoxicity can present PEGylated PEI-cholesterol conjugates as a potential carrier for delivery of poorly soluble chemotherapeutic agents such as SFB in HCC that certainly requires further investigations in vitro and in vivo

Recent Advances on Nanotechnology-Based Strategies for Prevention, Diagnosis, and Treatment of Coronavirus Infections

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is exponentially spreading across the world, leading to an outbreak of serious viral pneumonia. Antiviral therapies using chloroquine, hydroxychloroquine, and favipiravir have been approved by several countries to increase the quality of life of SARS-CoV-2-infected patients. Currently, several companies are intensively working on the production of coronavirus (CoV) vaccines, resulting in some specific vaccines that have been approved for CoV infections in humans. Nevertheless, efficient and specific prevention, treatment, and diagnosis are urgently required to combat the biological diversity and rapid mutation in CoV infections. Recently, significant attention has devoted to nanoformulation or nanoparticles (NPs) due to their specific features like high surface-to-volume ratio, drug encapsulation abilities, and specific optical properties to remove the complications of applied conventional therapeutic and diagnosis options. In this regard, NPs are increasingly used as new anti-CoV agents, vaccine carriers or adjuvants, and nanoscale biorecognition elements. The present review article provides a comprehensive discussion on the recent updates regarding the prevention, diagnosis, and treatment of different CoV infections with an emphasis on the application of NPs in vaccination, treatment, and diagnosis of CoV infections

Graphene Family Nanomaterials in Ocular Applications

Publisher Copyright: ©Graphene family nanomaterials (GFNs) are rapidly emerging for ocular applications due to their outstanding physicochemical properties. Since the eyes are very sensitive organs and the contact between the eyes and GFNs in eye drops, contact lenses, intraocular drug delivery systems and biosensors and even the workers handling these nanomaterials is inevitable, it is necessary to investigate their ocular toxicities and physiological interactions with cells as well as their toxicity mechanisms. The toxicity of GFNs can be extremely affected by their physicochemical properties, including composition, size, surface chemistry, and oxidation level as well as dose and the time of exposure. Up to now, there are several studies on the in vitro and in vivo toxicity of GFNs; however, a comprehensive review on ocular toxicity and applications of GFNs is missing, and a knowledge about the health risks of eye exposure to the GFNs is predominantly unspecified. This review highlights the ocular applications of GFNs and systematically covers the most recent advances of GFNs' physicochemical properties, in vitro and in vivo ocular toxicity, and the possible toxicity mechanisms as well as provides some perspectives on the potential risks of GFNs in material development and biomedical applications.Peer reviewe

Application of rapid and simple liquid chromatography method for determination of bioequivalence of generic lamotrigine tablets in healthy Iranian volunteers

A simple and rapid chromatography method was developed for determination of lamotrigine in human plasma. The method was used to compare the pharmacokinetic (PK) parameters of 50 mg generic and the reference lamotrigine (Lamictal) tablets in healthy Iranian volunteers. High performance liquid chromatography-ultraviolet method was developed and validated to determine lamotrigine concentration in plasma samples. The method was linear over the range of 0.1 to 15 μg/ml. The accuracy and precision were within the acceptable range. Limits of detection and quantification were calculated 0.06 and 0.10 μg/mL, respectively. A randomized, single-dose, two-period, two-sequence crossover study was carried out in healthy subjects receiving either the test or the reference products in each period. Pharmacokinetic parameters were determined using non-compartmental calculations. In vivo bioequivalency between the generic and the reference product was investigated according to the guidance for industry issued by US Food Drug Administration. AUC0-t, AUC0-∞ and Cmax were calculated for the generic product 12.50±2.76 μg.h/mL, 15.04±3.66 μg.h/mL and 0.38±0.08 μg/mL, respectively. The 90% confidence interval for the test/reference ratios were laid in the range of 0.80-1.25 for the log-transformed PK parameters. The generic product is bioequivalent and can be prescribed by practitioners while indicated, however the AUC and Cmax were lower in Iranian population if compared to the literature, which requires further investigations

Pharmaceutical Nanoemulsions and Their Potential Topical and Transdermal Applications: Pharmaceutical nanoemulsions potential applications

Topical and transdermal drug delivery systems are noninvasive and can be self-administered with the minimization of side-effects, have received increased attention during the past few years. Nanoemulsions, emulsions sized between 20-200 nm with narrow distributions, offer several advantages for topical and transdermal delivery of pharmaceutical agents including controlled droplet size, the ability to efficiently dissolve lipophilic drugs, enhanced skin permeation and extended release of lipophilic and hydrophilic drugs. Moreover, they exert good sensorial and physical properties such as complete dispersion on skin and skin hydration in cosmetic products. The review deals with nanoemulsion applications in topical and transdermaldrug and gene delivery

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs’ challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines

Biocompatibility of graphene oxide nanosheets functionalized with various amino acids towards mesenchymal stem cells

Graphene and its derivatives have gained popularity due to their numerous applications in various fields, such as biomedicine. Recent reports have revealed the severe toxic effects of these nanomaterials on cells and organs. In general, the chemical composition and surface chemistry of nanomaterials affect their biocompatibility. Therefore, the purpose of the present study was to evaluate the cytotoxicity and genotoxicity of graphene oxide (GO) synthesized by Hummer's method and functionalized by different amino acids such as lysine, methionine, aspartate, and tyrosine. The obtained nanosheets were identified by FT-IR, EDX, RAMAN, FE-SEM, and DLS techniques. In addition, trypan blue and Alamar blue methods were used to assess the cytotoxicity of mesenchymal stem cells extracted from human embryonic umbilical cord Wharton jelly (WJ-MSCs). The annexin V staining procedure was used to determine apoptotic and necrotic death. In addition, COMET and karyotyping techniques were used to assess the extent of DNA and chromosome damage. The results of the cytotoxicity assay showed that amino acid modifications significantly reduced the concentration-dependent cytotoxicity of GO to varying degrees. The GO modified with aspartic acid had the lowest cytotoxicity. There was no evidence of chromosomal damage in the karyotyping method, but in the comet assay, the samples modified with tyrosine and lysine showed the greatest DNA damage and rate of apoptosis. Overall, the aspartic acid-modified GO caused the least cellular and genetic damage to WJ-MSCs, implying its superior biomedical applications such as cell therapy and tissue engineering over GO