Green Synthesis and Biomedical Applications of ZnO Nanoparticles: Role of PEGylated-ZnO Nanoparticles as Doxorubicin Drug Carrier against MDA-MB-231(TNBC) Cells Line

The present study aimed to develop the synthesis of zinc oxide nanoparticles (ZnO-NPs) using the green method, with Aloe barbadensis leaf extract as a stabilizing and capping agent. In vitro antitumor cytotoxic activity, as well as the surface-functionalization of ZnO-NPs and their drug loading capacity against doxorubicin (DOX) and gemcitabine (GEM) drugs, were also studied. Morphological and structural properties of the produced ZnO-NPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersion X-ray diffraction (EDX), UV-Vis spectrophotometry, Fourier-transform infrared analysis (FTIR), and X-ray diffraction (XRD). The prepared ZnO-NPs had a hexagonal shape and average particle size of 20–40 nm, with an absorption peak at 325 nm. The weight and atomic percentages of zinc (50.58% and 28.13%) and oxygen (26.71% and 60.71%) were also determined by EDAX (energy dispersive x-ray analysis) compositional analysis. The appearance of the FTIR peak at 3420 m–1 confirmed the synthesis of ZnO-NPs. The drug loading efficiency (LE) and loading capacity (LC) of unstabilized and PEGylated ZnO-NPs were determined by doxorubicin (DOX) and gemcitabine (GEM) drugs. DOX had superior LE 65% (650 mg/g) and higher LC 32% (320 mg/g) than GEM LE 30.5% (30 mg/g) and LC 16.25% (162 mg/g) on ZnO-NPs. Similar observation was observed in the case of PEG-ZnO-NPs, where DOX had enhanced LE 68% (680 mg/g) and LC 35% (350) mg/g in contrast to GEM, which had LE and LC values of 35% (350 mg/g) and 19% (190 mg/g), respectively. Therefore, DOX was chosen to encapsulate nanoparticles, along with the untreated nanoparticles, to check their in vitro antiproliferative potential against the triple-negative breast cancer (TNBC) cell line (MDA-MB-231) through the MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay. This drug delivery strategy implies that the PEGylated biogenically synthesized ZnO-NPs occupy an important position in chemotherapeutic drug loading efficiency and can improve the therapeutic techniques of triple breast cancer.

Preparation and In Vitro Evaluation of a Nano Ultrasound Contrast Agent Targeting Pancreatic Cancer

To prepare a nano-sized ultrasound contrast agent that specifically targets pancreatic cancer cells and to evaluate its targeting effect In Vitro. PLGA-PEG-NHS was synthesized using PLGA, NHS, and PEG and detected using 1H-NMR. PLGA-PEG-NHS and PFOB were used to prepare PLGA nano contrast agent coated with PFOB by emulsification and volatilization, and then a hedgehog antibody was conjugated. The morphology of the nano contrast agent was observed using a transmission electron microscope, and its particle size and potential were measured using the dynamic light scattering method. The entrapment and drug loading efficiency of the nano contrast agent was measured using gas chromatography-mass spectrometry. The In Vitro release characteristics of the nano contrast agent was measured using the dialysis method. Human pancreatic cancer cell lines SW1990 and CFPAC1 were cultured in medium containing the nano contrast agent. The targeting ability of the nano contrast agent was qualitatively and quantitatively verified using fluorescence microscopy and flow cytometry. The average particle size of the targeted ultrasound contrast agent was 198.9 nm, zeta potential was −31.8 mv, entrapment rate was 63.7±3.9%, drug loading efficiency was 14.3±0.9%, and drug release was 85.3% in 48 h. In Vitro cell experiments showed that the targeted ultrasound contrast agent strongly bound to SW1990 cells with high expression of hedgehog antigen, but no specific binding was detected in CFPAC-1 cells which lack the hedgehog antigen. The nano ultrasound contrast agent prepared by emulsification and volatilization method can be potentially used for the diagnosis of pancreatic cancer.

FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

Design of thermoresponsive hydrogels by controlling the chemistry and imprinting of drug molecules within the hydrogel for enhanced loading and smart delivery of drugs

Various drug delivery techniques have contributed significantly to medical practice. In particular, molecular imprinting is a suitable method to increase the drug-loading efficiency in limited 3D spaces, such as hydrogels....

Solvent Diffusion Method: An Effective Approach to Formulate Nanosponges Loaded with Naproxen Sodium

Objective: Solubility of naproxen sodium is limited. In conventional dosage form it causes different gastro intestinal problems. To overcome these difficulties naproxen sodium loaded nano sponges were designed. Methodology: Nanosponges were formulated by using emulsion solvent evaporation technique. To obtain dispersion of nanosponges, homogenization of active drug, with specified quantities of polyvinyl alcohol, dichloromethane, ethyl cellulose and distilled, water was done. Compatibility among excipients and active drug was checked by FTIR and results didn’t show any interaction between them. 11 trial formulations were tested for poly dispersity, zeta potential, particle size and viscosity. Results: Results showed all formulations except NS9, NS10 and NS11 were in nano range. Formulation NS1 to NS6 fall in category of “mid poly dispersity” and formulation NS7 to NS11 were in the category of “very poly dispersity”. Values of Zeta potential of all formulations were in negative range -0.106 to -9.75 mV. The value of viscosity of all formulations were 0.8872. NS2 and NS3 were selected for further testing like Franz cell diffusion study, stability testing and drug loading efficiency. In Franz cell diffusion study, drug release for NS2= 89.62%, for NS3= 89.10% at 50 minutes’ time. Stability studies performed for the 21 days, NS2 and NS3 revealed slight change in percentage drug content at 4°C and 25°C, and major changes were observed at 45°C temperature. Drug loading efficiency was found in NS2= 97.659 % and for NS3= 98.901%. Conclusion: Nanosponges formulations loaded with naproxen sodium have successfully been prepared.

Molecular Dynamics Simulation, Characterization and In Vitro Drug Release of Isoniazid Loaded Poly-ε-caprolactone Magnetite Nanocomposite

Background: This study reports on the development of a controlled-release isoniazid (INH) drug delivery system using poly-є-caprolactone (PCL) functionalized magnetite-nanoparticles (MNPs), as a theoretical potential tool for tuberculosis (TB) chemotherapy. Method: The magnetite Fe3O4 core was fabricated by the co-precipitation method and coated with PCL by emulsion polymerization. INH was loaded onto the PCL-MNP surface to shape an INH-PCL-MNP nanocomposite. Deposing the INH on the nanocomposite surface was demonstrated through the molecular dynamics simulations. To investigate the stability of the polymer, the root-mean-square deviation (RMSD) and the radius of gyration (Rg) were calculated. The composite was characterized by Scanning electron microscopy (SEM) and X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Mycobacterium tuberculosis was used to assess the antimicrobial activity of the nanoparticles. The drug loading efficiency, drug content, and in-vitro release behavior of the INH-PCL-MNPs were evaluated by UV–Vis spectrophotometry. Results: RMSD of PCL show that the structure of polymer after 40 ns is stable. INH molecules interested to spend more time close to the polymer. Rg of PCL indicated that PCL folded and radius of gyration changed near 1nm. The drug loading efficiency and drug content of the NPs were 720±46 mg/g and 69.3±3.8 (%), respectively. The compound showed a strong level of activity in-vitro. The amount of drug release at all times was above the minimum inhibitory concentration (MIC) (6 μg/ml). Conclusion: INH-PCL-MNP nanocomposite have been effectively used as a potential tool to treat TB infections and a magnetic drug carrier system.

Superior antitumor effect of self-assembly supramolecular paclitaxel nanoparticles

Carrier-free paclitaxel nanoparticles with higher drug loading efficiency, less non-specific toxicity and more stable and durable antitumor effect of Ptx.

Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration and is easy for patients to develop into castration-resistant prostate cancer (CRPC) due to resistance to 18-24 months of androgen deprivation therapy (ADT). Moreover, it is hard to delivery Enz for low drug loading (DL) and encapsulation efficiency (EE). Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for castration-resistant prostate cancer (CRPC) intravenous treatment, with high drug loading efficiency and good biocompatibility.Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via a disulfide bond into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could promote the inhibition of cell growth in vitro against CRPC cells, while TP-GQDss alone did not show any obvious cytotoxicity on CRPC cells after 24 h of incubation. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as a intravenous therapy platform for CRPC.