Doughnut-shaped bovine serum albumin nanoparticles loaded with doxorubicin for overcoming multidrug-resistant in cancer cells (original) (raw)
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Molecules, 2020
Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results show...
Nanoparticular Antineoplastic Drug Delivery System Using Bovine Serum Albumin
2000
Targeted drug delivery is an effective means in cancer chemotherapy. Nanoparticulation is one of the useful means for targeted drug delivery. In the present investigation a broad spectrum anticancer drug methotrexate is nanoparticulated in a foreign protein bovine serum albumin. The particle size distribution was measured using a transmission electron microscope. Two sets of nanoparticles were prepared by varying Protein: drug ratio. The pattern of drug release from the nanoparticles were observed in pH 7.4 at 37o. A non-fickian type of release was observed from both sets.
Enzymatic degradation of bovine serum albumin nanoparticles for drug delivery
2010
Coacervation is a mild process for developing protein NPs. Bovine serum albumin (BSA) NPs formed via this technique were stabilized using poly-L-Lysine (PLL); short interfering ribonucleic acid (siRNA) was used as a model drug for encapsulation. Specific and non-specific degradation of these coated and uncoated BSA NPs were carried using matrix metalloproteinase-2 (MMP-2) and trypsin, respectively. The particles were characterized with atomic force microscopy, zetapotential, and photon correlation spectroscopy measurements. There was a significant increase in the zeta potential of BSA NPs upon coating. Trypsin digested the uncoated and coated BSA NPs and resulted in higher BSA release from the particles. However, MMP-2 treatment did not result in higher release of BSA from coated NPs despite the cleavability of coated polymer by MMP-2. This study described a method for obtaining BSA NPs in a controllable size range. Such particles showed degradability in the presence of trypsin and could be promising for targeted drug delivery applications. I would like to thank my lovely wife for her understanding and patience; her help in thesis writing was invaluable. My sincere thank to the lab members especially Guilin Wang and summer student, Haran Yogasundaram for their contributions in this project. Lastly, I would like to express gratitude to my parents to support me throughout my life in all my decisions.
Human serum albumin nanoparticles (HSA-NPs) are widely-used drug delivery systems with applications in various diseases, like cancer. For intravenous administration of HSA-NPs, the particle size, surface charge, drug loading and in vitro release kinetics are important parameters for consideration. This study focuses on the development of stable HSA-NPs containing the anti-cancer drug paclitaxel (PTX) via the emulsion-solvent evaporation method using a high-pressure homogenizer. The key parameters for the preparation of PTX-HSA-NPs are: the starting concentrations of HSA, PTX and the organic solvent, including the homogenization pressure and its number cycles, were optimized. Results indicate a size of 143.4 ˘ 0.7 nm and 170.2 ˘ 1.4 nm with a surface charge of´5.6 ˘ 0.8 mV and´17.4 ˘ 0.5 mV for HSA-NPs and PTX-HSA-NPs (0.5 mg/mL of PTX), respectively. The yield of the PTX-HSA-NPs was ~93% with an encapsulation efficiency of ~82%. To investigate the safety and effectiveness of the PTX-HSA-NPs, an in vitro drug release and cytotoxicity assay was performed on human breast cancer cell line (MCF-7). The PTX-HSA-NPs showed dose-dependent toxicity on cells of 52%, 39.3% and 22.6% with increasing concentrations of PTX at 8, 20.2 and 31.4 µg/mL, respectively. In summary, all parameters involved in HSA-NPs' preparation, its anticancer efficacy and scale-up are outlined in this research article.
Materials, 2021
Many studies are being performed to develop effective carriers for controlled cytostatic delivery wherein albumin is a promising material due to its tendency to accumulate near cancer cells. The novelty of this work involves the development of the synthesis methodology of albumin nanoparticles and their biological and physicochemical evaluation. Albumin particles were obtained via the salt-induced precipitation and K3PO4 was used as a salting-out agent. Various concentrations of protein and salting-out agent solutions were mixed using a burette or a syringe system. It was proved that the size of the particles depended on the concentrations of the reagents and the methodology applied. As a result of a process performed using a burette and 2 M K3PO4, albumin spheres having a size 5–25 nm were obtained. The size of nanospheres and their spherical shape was confirmed via TEM analysis. The use of a syringe system led to preparation of particles of large polydispersity. The highest albumi...
Nanomaterials, 2018
Solid lipid nanoparticles (SLNs) comprise a versatile drug delivery system that has been developed for the treatment of a variety of diseases. The present study will investigate the feasibility of entrapping an active doxorubicin prodrug (a squalenoyl-derivative) in SLNs. The doxorubicin derivative-loaded SLNs are spherically shaped, have a mean diameter of 300-400 nm and show 85% w/w drug entrapment efficiency. The effects on cell growth of loaded SLNs, free doxorubicin and the prodrug have been examined using cytotoxicity and colony-forming assays in both human ovarian cancer line A2780 wild-type and doxorubicin-resistant cells. Further assessments as to the treatment's ability to induce cell death by apoptosis have been carried out by analyzing annexin-V staining and the activation of caspase-3. The in vitro data demonstrate that the delivery of the squalenoyl-doxorubicin derivative by SLNs increases its cytotoxic activity, as well as its apoptosis effect. This effect was particularly evident in doxorubicin-resistant cells.
Layer-by-Layer Assembled Thin Film of Albumin Nanoparticles for Delivery of Doxorubicin
Protein nanoparticles (NPs) have found significant applications in drug delivery due to their inherent biocompatibility, which is attributed to their natural origin. In this study, bovine serum abumin (BSA) nanoparticles were introduced in multilayer thin film via layer-by-layer self-assembly for localized delivery of the anticancer drug Doxorubicin (Dox). BSA nanoparticles (∼100 nm) show a high negative zeta potential in aqueous medium (−55 mV) and form a stable dispersion in water without agglomeration for a long period. Hence, BSA NPs can be assembled on a substrate via layerby-layer approach using a positively charged polyelectrolyte (chitosan in acidic medium). The protein nature of these BSA nanoparticles ensures the biocompatibility of the film, whereas the availability of functional groups on this protein allows one to tune the property of the self-assembly to have a pH-dependent drug release profile. The growth of multilayer thin film was monitored by UV−visible spectroscopy, and the films were further characterized by atomic force microscopy (AFM) and field emission scanning electron microscopy (FESEM). The drug release kinetics of these BSA nanoparticles and their self-assembled thin film has been compared at a physiological pH of 7.4 and an acidic pH of 6.4.
Nanoparticles (NPs) have been developed as an important strategy to deliver low molecular-weight drugs, as well as biomacromolecules such as proteins or DNA. The body distribution of colloidal drug delivery systems was mainly influenced by two physicochemical properties namely particle size and surface characteristics. Particle size is a crucial parameter, in particular for the in vivo behavior of NPs after intravenous injection. The objective of the present study was the preparation of human serum albumin (HSA) nanoparticle (NP) by desolvation method and optimization of NP by applying the Taguchi method together with characterization of the NP bioproducts for drug delivery application. Several process parameters were examined to achieve a suitable size of NP such as pH, HSA concentration, organic solvent adding rate and the ratio of organic solvent/HSA solution. Taguchi method with L 16 orthogonal array robust design was implemented to optimize experimental conditions of the purpose. This approach facilitates the study of interaction of a large number of variables spanned by factors and their settings with a small number of experiments leading to considerable saving in time and cost for the process optimization. As a result of Taguchi analysis in this study, pH and ratio of organic solvent/HSA solution were the most influencing parameters on the particle size. The minimum size of NPs (53 nm) were obtained at pH 9, 75 mg.ml-1 HSA concentration, ratio of organic solvent/HSA solution of 4 and organic solvent adding rate of 1.5 ml.min-1. The mechanistic of the optimum conditions for preparing protein NPs and their characterization as drug delivery vehicles are discussed.
Biochimica Et Biophysica Acta - General Subjects, 2019
Human serum albumin (HSA) nanoparticles emerge as promising carriers for drug delivery. Among challenges, one important issue is the design of HSA nanoparticles with a low mean size of ca. 50 nm and having a high drug payload. The original strategy developed here is to use sacrificial mesoporous nanosilica templates having a diameter close to 30 nm to drive the protein nanocapsule formation. This new approach ensures first an efficient high drug loading (ca. 30%) of Doxorubicin (DOX) in the porous silica by functionalizing silica with an aminosiloxane layer and then allows the one-step adsorption and the physical cross-linking of HSA by modifying the silica surface with isobutyramide (IBAM) groups. After silica template removal, homogenous DOX-loaded HSA nanocapsules (30-60 nm size) with high drug loading capacity (ca. 88 %) are thus formed. Such nanocapsules are shown efficient in multicellular tumor spheroid models (MCTS) of human hepatocarcinoma cells by their significant growth inhibition with respect to controls. Such a new synthesis approach paves the way toward new protein based nanocarriers for drug delivery.
International Journal of Nanomedicine, 2011
This study deals with the preparation and investigation of a nanoscale delivery system for the anticancer drug doxorubicin (DOX) using its complexation with polyanionic carbohydrate dextran sulfate (DS). Dynamic light scattering, SEM, and zeta potential determination were used to characterize nanocomplexes. DOX-DS complexation was studied in the presence of ethanol as a hydrogen-bond disrupting agent, NaCl as an electrostatic shielding agent, and chitosan as a positively charged polymer. Thermodynamics of DOX-DS interaction was studied using isothermal titration calorimetry (ITC). A dialysis method was applied to investigate the release profile of DOX from DOX-DS nanocomplexes. Spherical and smooth-surfaced DOX-DS nanocomplexes (250-500 nm) with negative zeta potential were formed at a DS/DOX (w/w) ratio of 0.4-0.6, with over 90% drug encapsulation efficiency. DOX when complexed with DS showed lower fluorescence emission and 480 nm absorbance plus a 15 nm bathometric shift in its visible absorbance spectrum. Electrostatic hydrogen bonding and π-π stacking interactions are the main contributing interactions in DOX-DS complexation. Thermal analysis of DOX-DS complexation by ITC revealed that each DOX molecule binds with 3 DS glycosyl monomers. Drug release profile of nanocomplexes showed a fast DOX release followed by a slow sustained release, leading to release of 32% of entrapped DOX within 15 days. DOX-DS nanocomplexes may serve as a drug delivery system with efficient drug encapsulation and also may be taken into consideration in designing DOX controlled-release systems.