Search results for: drug delivery to the brain

Authors: Kaarunya Sampathkumar, Say Chye Joachim Loo

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Oral delivery is regarded as the facile method for the administration of active pharmaceutical ingredients (API) and drug carriers. In an initiative towards sustainable nanotechnology, an oral nano-delivery system has been developed that is made entirely of food-based materials and can also act as a site-specific delivery device depending on the stimulus encountered in different parts of the gastrointestinal tract (GIT). The delivery system has been fabricated from food grade polysaccharide materials like chitosan and starch through electrospraying technique without the use of any organic solvents. A nutraceutical extracted from an Indian medicinal plant, has been loaded into the nano carrier to test its efficacy in encapsulation and stimuli based release of the active ingredient. The release kinetics of the nutraceutical from the carrier was evaluated in simulated gastric, intestinal and colonic fluid and was found to be triggered both by the enzymes and the pH in each part of the intestinal tract depending on the polysaccharide being used. The toxicity of the nanoparticles on the intestinal epithelial cells was tested and found to be relatively safe for up to 24 hours at a concentration of 0.2 mg/mL with cellular uptake also being observed. The developed nano carrier thus serves as a promising delivery vehicle for targeted delivery to different parts of the GIT with the inherent conditions of the GIT itself acting as the stimulus. In addition, being fabricated from food grade materials, the carrier could be potentially used for the targeted delivery of nutrients through functional foods.

Keywords: bioavailability, chitosan, delivery systems, encapsulation

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Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

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Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

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Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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Authors: S. Bouameur, S. Chirani

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The aim of this study was to evaluate the potential use of EthylCellulose in the preparation of microspheres as a Drug Delivery System for sustained release of phenobarbital. The microspheres were prepared by solvent evaporation technique using ethylcellulose as polymer matrix with a ratio 1:2, dichloromethane as solvent and Polyvinyl alcohol 1% as processing medium to solidify the microspheres. Size, shape, drug loading capacity and entrapement efficiency were studied.

Keywords: phenobarbital, microspheres, ethylcellulose, polyvinylacohol

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Authors: N. Fuad, M. N. Taib, R. Jailani, M. E. Marwan

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In this paper, the comparison between k-Nearest Neighbor (kNN) algorithms for classifying the 3D EEG model in brain balancing is presented. The EEG signal recording was conducted on 51 healthy subjects. Development of 3D EEG models involves pre-processing of raw EEG signals and construction of spectrogram images. Then, maximum PSD values were extracted as features from the model. There are three indexes for the balanced brain; index 3, index 4 and index 5. There are significant different of the EEG signals due to the brain balancing index (BBI). Alpha-α (8–13 Hz) and beta-β (13–30 Hz) were used as input signals for the classification model. The k-NN classification result is 88.46% accuracy. These results proved that k-NN can be used in order to predict the brain balancing application.

Keywords: power spectral density, 3D EEG model, brain balancing, kNN

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Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Shiva Shakori Poshteh

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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.

Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery

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Authors: Simona Dostalova, Dita Munzova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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The boom of nanomedicine in recent years has led to the development of numerous new nanomaterials that can be used as nanocarriers in the drug delivery. These nanocarriers can either be synthetic or natural-based. The disadvantage of many synthetic nanocarriers is their toxicity in patient’s body. Protein cages that can naturally be found in human body do not exhibit such disadvantage. However, the release of cargo from some protein cages in target cells can be problematic. As a special type of protein cages can serve the capsid of many viruses, including phage. Phages infect bacterial cells; therefore they are not harmful to human cells. The targeting of phage particles to cancer cells can be solved by producing of empty phage capsids during which the targeting moieties (e.g. peptides) can be cloned into genes of phage capsid to decorate its surface. Moreover, the produced capsids do not contain viral nucleic acid and are therefore not infectious to beneficial bacteria in the patient’s body. The protein cage composed of viral capsid is larger than other frequently used apoferritin cage but its size is still small enough to benefit from passive targeting by Enhanced Permeability and Retention effect. In this work, bacteriophage λ was used, both whole and its empty capsid for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin, etoposide and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2 % maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000 g and 4 °C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 µg/ml). Free molecules of drugs were removed by dialysis. The encapsulation was verified using spectrophotometric and electrochemical methods. The amount of encapsulated drug linearly increased with the amount of applied drug (determination coefficient R2=0.8013). 76% of applied drug was encapsulated in phage λ particles (concentration of 10 µg/ml), even with the highest applied concentration of drugs, 200 µg/ml. Only 1% of encapsulated drug was detected in phage DNA. Similar results were obtained with encapsulation in phage empty capsid. Therefore, it can be concluded that the encapsulation of drugs into phage particles is efficient and mostly occurs by interaction of drugs with protein capsid.

Keywords: cytostatics, drug delivery, nanocarriers, phage capsid

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Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

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Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Razieh Khalafi

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The brain is the information processing centre of the human body. Stimuli in the form of information are transferred to the brain and then brain makes the decision on how to respond to them. In this research, we propose a new partial differential equation which analyses the EEG signals and make a relationship between the incoming stimuli and the brain response to them. In order to test the proposed model, a set of external stimuli applied to the model and the model’s outputs were checked versus the real EEG data. The results show that this model can model the EEG signal well. The proposed model is useful not only for modelling of EEG signal in case external stimuli but it can be used for modelling of brain response in case of internal stimuli.

Keywords: brain, stimuli, partial differential equation, response, EEG signal

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Authors: Alaa Hamed Salama, Rehab Nabil Shamma

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Introduction: Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim of this study was to review the aqueous-based formulation of drug-loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. This study investigated the synergistic performance of mixed polymeric micelles made of linear and branched poly (ethylene oxide)-poly (propylene oxide) for the more effective encapsulation of Lornoxicam (LX) as a hydrophobic model drug. Methods: The co-micellization process of 10% binary systems combining different weight ratios of the highly hydrophilic poloxamers; Synperonic® PE/P84, and Synperonic® PE/F127 and the hydrophobic poloxamine counterpart (Tetronic® T701) was investigated by means of photon correlation spectroscopy and cloud point. The drug-loaded micelles were tested for their solubilizing capacity towards LX. Results: Results showed a sharp solubility increase from 0.46 mg/ml up to more than 4.34 mg/ml, representing about 136-fold increase. Optimized formulation was selected to achieve maximum drug solubilizing power and clarity with lowest possible particle size. The optimized formulation was characterized by 1HNMR analysis which revealed complete encapsulation of the drug within the micelles. Further investigations by histopathological and confocal laser studies revealed the non-irritant nature and good corneal penetrating power of the proposed nano-formulation. Conclusion: LX-loaded polymeric nanomicellar formulation was fabricated allowing easy application of the drug in the form of clear eye drops that do not cause blurred vision or discomfort, thus achieving high patient compliance.

Keywords: confocal laser scanning microscopy, Histopathological studies, Lornoxicam, micellar solubilization

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Lakshmi Sirisha Kotikalapudi

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Atenolol, the widely used antihypertensive drug is ionisable and degrades in the acidic environment of the GIT lessening the bioavailability. Transdermal route may be selected as an alternative to enhance the bioavailability. Half-life of the drug is 6-7 hours suggesting the requirement of prolonged release of the drug. The present work of transdermal niosomal gel aims to extend release of the drug and increase the bioavailability. Ethanol injection method was used for the preparation of niosomes using span-60 and cholesterol at different molar ratios following central composite design. The prepared niosomes were characterized for size, zeta-potential, entrapment efficiency, drug content and in-vitro drug release. Optimized formulation was selected by statistically analyzing the results obtained using the software Stat-Ease Design Expert. The optimized formulation also showed high drug retention inside the vesicles over a period of three months at a temperature of 4 °C indicating stability. Niosomes separated as a pellet were dried and incorporated into the hydrogel prepared using chitosan a natural polymer as a gelling agent. The effect of various chemical permeation enhancers was also studied over the gel formulations. The prepared formulations were characterized for viscosity, pH, drug release using Franz diffusion cells, and skin irritation test as well as in-vivo pharmacological activities. Atenolol niosomal gel preparations showed the prolonged release of the drug and pronounced antihypertensive activity indicating the suitability of niosomal gel for topical and systemic delivery of atenolol.

Keywords: atenolol, chitosan, niosomes, transdermal

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Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

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Authors: Sofia Matoug, Amr Abdel-Dayem

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This paper presents a comprehensive survey of recent research studies to segment and classify brain MR (magnetic resonance) images in order to detect significant changes to brain ventricles. The paper also presents a general framework for detecting regions that atrophy, which can help neurologists in detecting and staging Alzheimer. Furthermore, a prototype was implemented to segment brain MR images in order to extract the region of interest (ROI) and then, a classifier was employed to differentiate between normal and abnormal brain tissues. Experimental results show that the proposed scheme can provide a reliable second opinion that neurologists can benefit from.

Keywords: Alzheimer, brain images, classification techniques, Magnetic Resonance Images MRI

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Authors: Jolanta Pulit-Prociak, Olga Dlugosz, Marcin Banach

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The toxicity of bare zinc oxide nanoparticles used as drug carriers may be the result of releasing zinc ions. Thus, zinc oxide nanoparticles modified with galactose were obtained. The process of their formation was conducted in the microwave field. The physicochemical properties of the obtained products were studied. The size and electrokinetic potential were defined by using dynamic light scattering technique. The crystalline properties were assessed by X-ray diffractometry. In order to confirm the formation of the desired products, Fourier-transform infrared spectroscopy was used. The releasing of zinc ions from the prepared products when comparing to the bare oxide was analyzed. It was found out that modification of zinc oxide nanoparticles with galactose limits the releasing of zinc ions which are responsible for the toxic effect of the whole carrier-drug conjugate.

Keywords: nanomaterials, zinc oxide, drug delivery system, toxicity

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Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

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Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

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Authors: Ravi Sheshala, Annie Lee, Ai Lin Ong, Ling Ling Cheu, Thiagarajan Madheswaran, Thankur R. R. Singh

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The objectives of the present research work were to develop and characterize biodegradable controlled release photo cross-linked implants of Triamcinolone Acetonide (TA) for the treatment of chronic ocular diseases. The photo cross-linked implants were prepared using film casting technique by mixing TA (2.5%) polyethylene glycol diacrylate (PEGDA 700), pore formers (mannitol, maltose, and gelatin) and the photoinitiator (Irgacure 2959). The resulting mixture was injected into moulds using 21 G and subjected to photocrosslinking at 365 nm. Scanning electron microscopy results demonstrated that more pores were formed in the films with the increase in the concentration of pore formers from 2%-10%. The maximum force required to break the films containing 2-10% of pore formers were determined in both dry and wet conditions using texture analyzer and found that films in a dry condition required a higher force to break compared to wet condition and blank films. In vitro drug release from photo cross-linked films were determined by incubating samples in 50 ml PBS pH 7.4 at 37 C and the samples were analyzed for drug release by HPLC. The films demonstrated a biphasic release profile i.e. an initial burst release (<20%) on the first day followed by a constant and continuous drug release in a controlled manner for 42 days. The drug release from all formulations followed the first-order release pattern and the combination of diffusion and erosion release mechanism. In conclusion, the developed formulations were able to provide controlled drug delivery to treat the chronic ocular diseases.

Keywords: controlled release, ophthalmic, PEGDA, photocrosslinking, pore formers

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Authors: Leila Asadollahi

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Dry powder inhalers (DPIs) have come a long way since their creation, starting with the Spinhaler Fisons in 1967. For optimal performance, it is important to consider the interplay between formulation, device, and patient. DPIs have shown great potential in treating systemic disorders, as evidenced by their success in clinical practices. Ongoing clinical trials and market availability of DPI products for systemic disease treatment are also examined. Furthermore, the current COVID-19 pandemic has sparked increased interest in dry powder inhalation as a potential avenue for vaccines and antiviral drugs, prompting further exploration of its applications. To achieve optimal treatment outcomes for respiratory diseases, a thorough understanding of the various types of DPIs currently available is crucial. These include single-dose, multiple-unit dose, and multi-dose DPIs. This informative article delves into the administration of drugs via inhalation, examining its diverse routes of administration. Additionally, it illuminates the exciting advancements in inhalation delivery systems and investigates the latest therapeutic approaches for the treatment of respiratory ailments. Additionally, the article discusses the historical development of DPIs and the need for improved designs to enhance efficacy and patient adherence. The potential of DPIs in treating systemic diseases is also examined. Overall, this review provides valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders. The review aims to provide valuable insights into the advancements, challenges, and future prospects of inhalation drug delivery systems, highlighting the potential they hold for respiratory and systemic disorders.

Keywords: dry powder inhalers (DPIs), respiratory diseases, systemic disorders, pulmonary drug delivery

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Authors: Bruno Baptista, Andreia S. R. Oliveira, Patricia V. Mendonca, Jorge F. J. Coelho, Fani Sousa

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Drug delivery systems are designed to allow adequate protection and controlled delivery of drugs to specific locations. These systems aim to reduce side effects and control the biodistribution profile of drugs, thus improving therapeutic efficacy. This study involved the synthesis of polymeric nanoparticles, based on amphiphilic diblock copolymers, comprising a biocompatible, poly (oligo (ethylene oxide) methyl ether methacrylate (POEOMA) as hydrophilic segment and a pH-sensitive block, the poly (2-diisopropylamino)ethyl methacrylate) (PDPA). The objective of this work was the development of polymeric pH-responsive nanoparticles to encapsulate and carry small RNAs as a model to further develop non-coding RNAs delivery systems with therapeutic value. The responsiveness of PDPA to pH allows the electrostatic interaction of these copolymers with nucleic acids at acidic pH, as a result of the protonation of the tertiary amine groups of this polymer at pH values below its pKa (around 6.2). Initially, the molecular weight parameters and chemical structure of the block copolymers were determined by size exclusion chromatography (SEC) and nuclear magnetic resonance (1H-NMR) spectroscopy, respectively. Then, the complexation with small RNAs was verified, generating polyplexes with sizes ranging from 300 to 600 nm and with encapsulation efficiencies around 80%, depending on the molecular weight of the polymers, their composition, and concentration used. The effect of pH on the morphology of nanoparticles was evaluated by scanning electron microscopy (SEM) being verified that at higher pH values, particles tend to lose their spherical shape. Since this work aims to develop systems for the delivery of non-coding RNAs, studies on RNA protection (contact with RNase, FBS, and Trypsin) and cell viability were also carried out. It was found that they induce some protection against constituents of the cellular environment and have no cellular toxicity. In summary, this research work contributes to the development of pH-sensitive polymers, capable of protecting and encapsulating RNA, in a relatively simple and efficient manner, to further be applied on drug delivery to specific sites where pH may have a critical role, as it can occur in several cancer environments.

Keywords: drug delivery systems, pH-responsive polymers, POEOMA-b-PDPA, small RNAs

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Authors: Ardiansyah I. Ryan, Ashsholih K. R., Fathurrohman G. R., Kurniadi M. R., Huda P. A

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The burden of brain-related disease is very high. There are a lot of brain-related diseases with limited treatment result and thus raise the burden more. The Parkinson Disease (PD), Mental Health Problem, or Paralysis of extremities treatments had risen concern, as the patients for those diseases usually had a low quality of life and low chance to recover fully. There are also many other brain or related neural diseases with the similar condition, mainly the treatments for those conditions are still limited as our understanding of the brain function is insufficient. Brain Implant Technology had given hope to help in treating this condition. In this paper, we examine the current update of the brain implant technology. Neurotechnology is growing very rapidly worldwide. The United States Food and Drug Administration (FDA) has approved the use of Deep Brain Stimulation (DBS) as a brain implant in humans. As for neural implant both the cochlear implant and retinal implant are approved by FDA too. All of them had shown a promising result. DBS worked by stimulating a specific region in the brain with electricity. This device is planted surgically into a very specific region of the brain. This device consists of 3 main parts: Lead (thin wire inserted into the brain), neurostimulator (pacemaker-like device, planted surgically in the chest) and an external controller (to turn on/off the device by patient/programmer). FDA had approved DBS for the treatment of PD, Pain Management, Epilepsy and Obsessive Compulsive Disorder (OCD). The target treatment of DBS in PD is to reduce the tremor and dystonia symptoms. DBS has been showing the promising result in animal and limited human trial for other conditions such as Alzheimer, Mental Health Problem (Major Depression, Tourette Syndrome), etc. Every surgery has risks of complications, although in DBS the chance is very low. DBS itself had a very satisfying result as long as the subject criteria to be implanted this device based on indication and strictly selection. Other than DBS, there are several brain implant devices that still under development. It was included (not limited to) implant to treat paralysis (In Spinal Cord Injury/Amyotrophic Lateral Sclerosis), enhance brain memory, reduce obesity, treat mental health problem and treat epilepsy. The potential of neurotechnology is unlimited. When brain function and brain implant were fully developed, it may be one of the major breakthroughs in human history like when human find ‘fire’ for the first time. Support from every sector for further research is very needed to develop and unveil the true potential of this technology.

Keywords: brain implant, deep brain stimulation (DBS), deep brain stimulation, Parkinson

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Authors: S. S. Pati, L. Herojit Singh, A. C. Oliveira, V. K. Garg

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Chitosan functionalized Fe3O4-Au core shell nanoparticles have been prepared using a two step wet chemical approach using NaBH4 as reducing agent for formation of Au inethylene glycol. X-ray diffraction studies shows individual phases of Fe3O4 and Au in the as prepared samples with crystallite size of 5.9 and 11.4 nm respectively. The functionalization of the core-shell nanostructure with Chitosan has been confirmed using Fourier transform infrared spectroscopy along with signatures of octahedral and tetrahedral sites of Fe3O4 below 600cm-1. Mössbauer spectroscopy shows decrease in particle-particle interaction in presence of Au shell (72% sextet) than pure oleic coated Fe3O4 nanoparticles (88% sextet) at room temperature. At 80K, oleic acid coated Fe3O4 shows only sextets whereas the Chitosan functionalized Fe3O4 and Chitosan functionalized Fe3O4@Au core shell show presence of 5 and 11% doublet, respectively.

Keywords: core shell, drug delivery, gold nanoparticles, magnetic nanoparticles

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Authors: U.V. Suryawanshi, S.S. Chowhan, U.V Kulkarni

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Accuracy of segmentation methods is of great importance in brain image analysis. Tissue classification in Magnetic Resonance brain images (MRI) is an important issue in the analysis of several brain dementias. This paper portraits performance of segmentation techniques that are used on Brain MRI. A large variety of algorithms for segmentation of Brain MRI has been developed. The objective of this paper is to perform a segmentation process on MR images of the human brain, using Fuzzy c-means (FCM), Kernel based Fuzzy c-means clustering (KFCM), Spatial Fuzzy c-means (SFCM) and Improved Fuzzy c-means (IFCM). The review covers imaging modalities, MRI and methods for noise reduction and segmentation approaches. All methods are applied on MRI brain images which are degraded by salt-pepper noise demonstrate that the IFCM algorithm performs more robust to noise than the standard FCM algorithm. We conclude with a discussion on the trend of future research in brain segmentation and changing norms in IFCM for better results.

Keywords: image segmentation, preprocessing, MRI, FCM, KFCM, SFCM, IFCM

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

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Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

Procedia PDF Downloads 305