Modares Journal of Biotechnology

Abstract Curcumin, a potent antioxidant extracted from the turmeric plant, is known for its ability to suppress reactive oxygen species (ROS) through activation of antioxidant response elements. However, its clinical utility is limited by poor solubility and rapid elimination. In this study, we aimed to enhance the solubility and bioavailability of curcumin by encapsulating it in fifth-generation polyamidoamine dendrimer nanoparticles. UV-Vis and fluorescence spectroscopy confirmed successful encapsulation, with an average nanoparticle size of 275 nm and a positive surface charge of 8 mV. The nanocarrier exhibited a loading capacity of approximately curcumin6 mol per dendrimer 1mol and achieved complete drug release within 72 hours. Cellular uptake assays using a live/dead assay revealed superior uptake of the nanocarrier compared to free curcumin, leading to a significant reduction in cellular ROS levels and apoptosis. Furthermore, in a model of induced oxidative stress using H2O2, curcumin-loaded dendrimer nanoparticles significantly reduced cellular ROS levels compared to free curcumin. These findings highlight the potential of this nanocarrier as an effective and intelligent system for delivering water-insoluble drugs, offering a promising approach for improving the therapeutic efficacy of curcumin.

Abstract Aims: Curcumin is a natural molecule that due to its various curative effects including antibacterial properties, it can be used as a medicine, albeit after reducing its disadvantages. The aim of the present study is to develop a method for preparation of nanoparticles of curcumin using PAA, PVA, and PEI polymers with a view to improve its stability, increasing bioavailability and aqueous solubility as well as study its effectiveness against methicillin-resistant to Staphylococcus aureus.
Materials & Methods: In order to synthesize polymeric nanoparticles including curcumin with the nano-precipitation method, optimizing the effective concentration of polymer, curcumin, and water were determined by using the Response Surface Method (RSM). Synthesized nanoparticles were characterized by Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS) and zeta potential measurement methods. Furthermore, minimal concentration inhibitory of synthesized nanoparticles against the Staphylococcus aureus resistant to methicillin was measured.
Findings: The created nanoparticles were round, discrete and smooth in surface morphology and the average particle size for PAA, PVA, and PEI were 149±7nm, 175±8nm, and 184±9nm respectively. The minimum inhibitory concentration for PAA, PVA and PEI nanoparticles against the Staphylococcus aureus were 0.480±0.024, 0.390±0.019 and 0.340±0.017mg/ml. The concentration of solvent, polymer, and curcumin was important to obtain small size particles.
Conclusion: The results indicated that the water solubility of curcumin significantly improved by particle size reduction up to the nano range. The inhibitory property of curcumin nanoparticles has greatly increased due to the smaller particle size and their increased penetration into the bacteria and nanoparticles loaded with curcumin could be a promising drug carrier for the treatment of cancer, infections and other diseases.

Abstract Nanotechnology is currently one of the promising approaches for cancer diagnosis and treatment. Among different materials that so far have been used for drug delivery, the systems based on the polymers are more attractive, due to their simple manufacturing processes and diversity in polymer functionalization and modification methods. Polyethyleneglycol (PEG) and polycaprolactone (PCL) are two FDA approved and biocompatible synthetic polymers which frequently have been used in the pharmaceutical industry. Apart from the delivery carriers, the active ingredient’s safety is also very challenging in case of cancer therapeutics. The chemotherapy agent’s side effects are one of the main patients’ death in many cancers. The naturally extracted curcumin is one of the most interesting anti-cancer agents with a proven selective effect on the cancerous cells which results in minimum side effects during the treatment. Curcumin has been tested as the main agent or in combination therapy of various cancers. Numerous studies have shown the safety and efficacy of curcumin at different administered doses. However, the main obstacle in the application of curcumin is its low aqueous solubility and low and variable bioavailability after administration. For that, in this study, we tried to enhance the solubility of curcumin using a novel diblock copolymer of PEG-PCL nanoparticulate system. At first, the PEG-PCL copolymer was synthesized and then characterized by GPC, FTIR, and H NMR methods. After that, curcumin was loaded in the micellar structure of PEG-PCL at an optimized encapsulation approach and then the toxicity of the prepared nanoparticles was assessed in MCF-7 cell culture. The results showed that the prepared nanoparticles could efficiently entrap the hydrophobic molecules of curcumin, improve its solubility and increase in vitro activity against cancer cell line.

Abstract Antioxidant, anticancer, anti-inflammatory, and anti-microbial activities are evidences for the invaluable benefit of this herbal extract in human health and therapy. The anticancer effect of curcumin is due to the targeting of a wide range of cellular and molecular pathways involved in cancer progression. However, the limited solubility, low bioavailability and rapid metabolism of curcumin have a serious negative impact on its therapeutic application. In this research, a nano-carrier with appropriate delivery features, prepared through the conjugation of curcumin to the surface of a polyamidoamine dendrimer at generation 4 (PAMAM). The structure of the synthesized dendrimeric curcumin was confirmed by FT-IR and ¹H-NMR methods. The particles size and zeta potential were measured by Zetasizer. The loading rate of curcumin molecules on nano-carrier investigated and the cell viability, intracellular reactive oxygen species and induction of apoptosis were evaluated using MTT assay and flow cytometry technique in the follows. The results of this study showed that the prepared dendrimeric curcumin had a hydrodynamic diameter of about 100 nm. The results show that the rate of curcumin loading on this nanostructure system was about four curcumin molecules per each dendrimer. Cell experiments indicated that the toxicity, cellular reactive oxygen species (ROS), and apoptosis caused by dendrimeric nano-carrier were higher than free curcumin. Better performance of dendrimer-Nano-carrier was been through the improvement of physicochemical properties and increased curcumin solubility. Overall, it seems that the prepared dendrimeric curcumin is able to significantly improve the delivery of hydrophobic drugs on cancerous cells.

Abstract In this study, nano drug delivery system based on graphene oxide and reduced graphene oxide- polyglycerol hybrids were constructed. Functionalization of nano graphene oxide and reduced graphene oxide was accomplished through noncovalent interaction between the π conjugated system of graphene materials and the aromatic segment in the focal point of polyglycerol polymer. Polyglycerol is a hydrophilic and biocompatible polymer that its conjugation with graphene materials was increased the colloidal stability and decreased the nonspecific interaction of graphene materials. Curcumin as an anticancer hydrophobic natural drug with low systemic bioavailability was simply loaded on these nanohybrids via π-π stacking force between the π conjugated systems of graphene materials and curcumin. Result showed that loading capacity of curcumin for reduced graphene oxide hybrid (49%) is higher than graphene oxide hybrid due to restored of π conjugated system in reduced graphene oxide. Anticancer efficiency of these drug hybrids was investigated by MTT assay. Results showed that these drug carriers have sufficient biocompatibility. Also these nano drug delivery systems showed a cytotoxic effect that was comparable to that of free curcumin. The reduced graphene oxide hybrid is preferred for delivery of curcumin due to its higher loading capacity that can provide efficient dose of drug in low level of carrier