New Nanoparticle Research Articles

Pioglitazone Nanoparticles Development, Characterization, Optimization, and a Zebrafish Model Evaluation of its Teratogenic Safety

Background: New nanoparticles (NPs) and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. Nanomaterials are materials with d50 value from 1 to 100nm. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. background: New nanoparticles and biomaterials are utilized more frequently in biological research for vaccinations, diagnostic procedures, and drug administration. They are also found in various consumer goods, the environment, and work. Thus, it has become crucial for the appropriate development of nanotechnology to assess the safety and potential therapeutic applications of these nanomaterials. The BCS Cass II medication pioglitazone hydrochloride, used to treat hypoglycaemia, has poor bioavailability after oral treatment because it dissolves poorly in gastrointestinal fluids. Objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes. objective: This study aimed to create adjusted pioglitazone nanoparticles to decrease dose-related side effects and prolong its release when used against type 2 diabetes Methods: The emulsion solvent evaporation approach was used to create nanoparticles utilising HPMC K15M and Eudragit S100 as polymers, and Tween 80 as a surfactant. On framed nanoparticles, in-vitro evaluation approaches for drug-polymer compatibility, percentage yield, particle size, zeta potential, polydispersity index, surface morphology, encapsulation effectiveness, and in-vitro drug release study were used, followed by in-vivo acute toxicity experiment. Conclusion: From the obtained data, it can be said that a suitable optimized formulation of pioglitazone nanoparticles was prepared, which offered extended drug release of 95% in 10 hours.

Thymoquinone Nanoparticles (TQ-NPs) in Kidney Toxicity Induced by Ehrlich Ascites Carcinoma (EAC): An In Vivo Study.

Cisplatin (Cis) is potent chemotherapy used to treating already many different types of cancer; however, it is found to correlate with nephrotoxicity and other adverse health consequences. Thymoquinone (TQ) is an antioxidant and anti-inflammatory molecule that may defend against the consequences of different chemotherapies. Thymoquinone uses, although, are negatively impacted by its weak solubility and inadequate biological availability. This investigation examined the efficacy of a new nanoparticle (NP) absorbing TQ in an Ehrlich Ascites Carcinoma (EAC) mice model to address its low solubility, enhance its bioavailability, and protect against Cis-induced nephrotoxicity. Following 4 treatment groups were included in this research: (1) control, (2) EAC, (3) EAC + Cis + Thymoquinone nanoparticle (TQ-NP) treated, and (4) EAC + Cis-treated. The study revealed that TQ-NP was efficacious in avoiding Cis-induced kidney problems in EAC mice, as well as restoring kidney function and pathology. Thymoquinone nanoparticle considerably reduced Cis-induced oxidative damage in renal tissue by augmenting antioxidant levels. According to tumor weight and histological investigation results, TQ-NP did not impair Cis's anticancer efficacy. Thymoquinone nanoparticle might be used as a potential drug along with Cis anticancer therapy to reduce nephrotoxicity and other side effects while maintaining Cis anticancer properties.

Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate Lupus Disease in Fcgr2b-/- Mice by Mediating Antigen-Specific Immune Tolerance.

Dendritic cells (DCs) are the most potent antigen-presenting cells that have multifaceted functions in the control of immune activation and tolerance. Hyperresponsiveness and altered tolerogenicity of DCs contribute to the development and pathogenesis of system lupus erythematosus (SLE); therefore, DC-targeted therapies aimed at inducing specific immune tolerance have become of great importance for the treatment of SLE. This study developed a new nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for target-oriented delivery to DCs in situ. PDMAEMA-PLGA NPs provided sustained drug release and exhibited immunosuppressive activity in FLT3L and GM-CSF-derived bone marrow in conventional DCs (BM-cDCs). PDMAEMA-PLGA NPs improved dexamethasone capability to convert wild-type and Fcgr2b-/- BM-cDCs from an immunogenic to tolerogenic state, and BM-cDCs treated with dexamethasone-incorporated PDMAEMA-PLGA NPs (Dex-NPs) efficiently mediated regulatory T cell (Treg) expansion in vitro. Dex-NP therapy potentially alleviated lupus disease in Fcgr2b-/- mice by mediating Foxp3+ Treg expansion in an antigen-specific manner. Our findings substantiate the superior efficacy of DC-targeted therapy using the PDMAEMA-PLGA NP delivery system and provide further support for clinical development as a potential therapy for SLE. Furthermore, PDMAEMA-PLGA NP may be a versatile platform for DC-targeted therapy to induce antigen-specific immune tolerance to unwanted immune responses that occur in autoimmune disease, allergy, and transplant rejection.

Design and formulation of Eudragit-coated zein/pectin nanoparticles for the colon delivery of resveratrol

Resveratrol (RSV) is a naturally occurring polyphenolic phytoalexin with beneficial effects on human health, including the treatment and prevention of ulcerative colitis and cancer. This work proposes the formulation and characterization of new nanoparticles (NPs) for the specific colon delivery of RSV. RSV was encapsulated in zein (Z) NPs, coated by a hydrophilic pectin (P) shell to significantly increase the dissolution rate of RSV in aqueous environments. Since the dissolved drug was strongly degraded in a simulated gastrointestinal tract, the ZP-NPs were coated with Eudragit S 100. The coated particles, even if aggregated, had a spherical morphology with diameters in the 100–200 nm range. Release studies of RSV from the ZP coated NPs evidenced their potential ability to induce a specific colon delivery of this drug so that this formulation can be proposed to enrich natural food products to enhance their preventive and therapeutic effects in the lower GI tract.

Abstract 1723: Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy

Abstract Background: Activation of the innate immune system and natural killer (NK) cells has been a key effort in cancer immunotherapy research. Several NK-cell-targeted therapeutics are under clinical investigation. Current research is focused on bispecific antibodies that can bind to and target both tumor cells and NK cells. However, NK activation remains a key challenge. One approach is to simultaneously co-activate more than one NK cell stimulatory molecule, such as 4-1BB and CD16 (FcγRIII), to increase immune activation. To achieve this, we developed a new nanoparticle (NP)-based trispecific NK cell engager (nano-TriNKE) platform that can target epidermal growth factor receptor (EGFR) overexpressing tumors and promote the recruitment and activation of NK cells to eradicate these cancer cells. Moreover, the nanoengager platform allows the targeted delivery of chemotherapeutics such as epirubicin (EPI) to further improve the therapeutic efficacy. Methods: EGFR-targeted drug-free/EPI-encapsulated nano-TriNKEs were prepared by conjugating cetuximab (anti-EGFR), anti-4-BB, and anti-CD16 agonistic antibodies to PEG-PLGA NPs. Their binding specificities were evaluated in expanded murine NK cells, EGFR-overexpressed A431 (epidermoid carcinoma), MB468 (mammary gland adenocarcinoma), and HT29 (colorectal adenocarcinoma) cells in vitro. The in vitro NK cell anticancer activities in nano-TriNKE-pretreated A431, MB468, and HT29 cells were evaluated via viability assays. We also performed comprehensive in vivo efficacy studies in A431, MB468, and HT29 tumor model to investigate the anticancer activities of EGFR-targeted drug-free/EPI-encapsulated nano-TriNKEs. Further biodistribution and mechanistic studies were performed to verify the anticancer activities of nano-TriNKEs. Results: In vitro binding assay confirmed that the EGFR-targeted nano-TriNKEs bind selectively to EGFR-overexpressed cancer cells. In vitro anticancer activity studies demonstrated that effective NK cell activation can be achieved by spatiotemporal co-activation of CD16 and 4-1BB stimulatory molecules on NK cells with nanoengagers, and that the nanoengagers are more effective than free antibodies. Comprehensive in vivo efficacy studies in A431, MB468, and HT29 tumor models demonstrated that the EGFR-targeted nano-TriNKEs can augment both NK activating agents and chemotherapy as highly effective anticancer agents, providing robust chemoimmunotherapy against a broad range of EGFR-overexpressed cancers. Conclusions: Our data demonstrated that nano-TriNKEs are more effective in NK activation than free agonistic antibodies, and that the nanoengager platform provides more effective biological targeting, which is critical in NK-mediated cancer immunotherapy. Citation Format: Kin Man Au, Steven Park, Andrew Wang. Trispecific natural killer cell nanoengagers for targeted chemoimmunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1723.

Ultrasmall superparamagnetic iron oxide nanoparticles with titanium-N,N-dialkylcarbamato coating

This work deals with the preparation and physical-chemical characterization of new ultrasmall iron oxide superparamagnetic nanoparticles (USPIONs) functionalized with titanium-N,N-dialkylcarbamato. The preparation was performed starting with monodispersed USPIONs covered with oleic acid, synthesized by thermal-decomposition, and subsequently functionalized with metal-carbamato by a ligand-exchange reaction. The surface and coating structure was characterized by infrared (FT-IR) spectroscopy on the solid powders and thermogravimetry (TG) coupled with an FT-IR detector in order to better investigate the self-assembling properties of the coating. A detailed dimensional and morphological study was carried out by transmission electron microscopy (TEM) and atomic force microscopy (AFM) analysis. Zero-field-cooled (ZFC) and field-cooled (FC) magnetic susceptibility curves as well as the magnetization behavior as a function of temperature were investigated on both the starting oleic-USPIONs and those covered by titanium-N,N-dialkylcarbamato. These results confirmed the superparamagnetic properties of the new nanoparticles (NPs), highlighting the quite high saturation value of the magnetization. Based on the results obtained by combining different experimental techniques, a model of the coating structure and ligand organization around the magnetic core is proposed for both NPs, i.e. the starting USPIONs covered by oleic acid and the new USPIONs functionalized by titanium-N,N-dialkylcarbamato.

Electrokinetic characterization of superparamagnetic nanoparticle–aptamer conjugates: design of new highly specific probes for miniaturized molecular diagnostics

With the view of designing new nanoparticle (NP)-aptamer conjugates and proving their suitability as biorecognition tools for miniaturized molecular diagnostics, new maghemite-silica core-shell NP-aptamer conjugates were characterized for the first time in terms of grafting rate and colloidal stability under electrophoretic conditions using capillary electrophoresis. After the grafting rate (on the order of six to 50) of the lysozyme-binding aptamer had been estimated, the electrophoretic stability and peak dispersion of the resulting oligonucleotide-NP conjugates were estimated so as to determine the optimal separation conditions in terms of buffer pH, ionic strength and nature, as well as temperature and electric field strength. The effective surface charge density of the NPs was close to zero for pH lower than 5, which led to some aggregation. The NPs were stable in the pH range from 5 to 9, and an increase in electrophoretic mobility was evidenced with increasing pH. Colloidal stability was preserved at physiological pH for both non-grafted NPs and grafted NPs in the 10-100 mM ionic strength range and in the 15-60 °C temperature range. A strong influence of the nature of the buffer counterion on NP electrophoretic mobility and peak dispersion was evidenced, thus indicating some interactions between buffer components and NP-aptamer conjugates. Whereas an electric field effect (50-900 V cm(-1)) on NP electrophoretic mobility was evidenced, probably linked to counterion dissociation, temperature seems to have an appreciable effect on the zeta potential and aptamer configuration as well. This information is crucial for estimating the potentialities of such biorecognition tools in electrophoretic systems.

A comparative study of chitosan and chitosan/cyclodextrin nanoparticles as potential carriers for the oral delivery of small peptides☆

The aim of this study was to characterize new nanoparticles (NPs) containing chitosan (CS), or CS/cyclodextrin (CDs), and evaluate their potential for the oral delivery of the peptide glutathione (GSH). More precisely, NP formulations composed of CS, CS/alpha-CD and CS/sulphobutyl ether-beta-cyclodextrin (SBE(7m)-beta-CD) were investigated for this application. CS/CD NPs showed particle sizes ranging from 200 to 500nm. GSH was loaded more efficiently in CS/SBE(7m)-beta-CD NPs by forming a complex between the tripeptide and the CD. X-ray Photoelectron Spectroscopy (XPS) analysis suggested that GSH is located in the core of CS/SBE(7m)-beta-CD NPs and that it is almost absent from the NP surface. Release studies performed in vitro at pH 1.2 and pH 6.8 showed that NP release properties can be modulated by selecting an appropriate CD. Transport studies performed in the frog intestine model confirmed that both CS and CS/CD nanoparticles could induce permeabilization of the intestinal epithelia. However, CS/SBE(7m)-beta-CD NPs provided absorption-enhancing properties in all segments of the duodenum, whereas CS NPs effect was restricted to the first segment of the duodenum. From the data obtained, we believe that CS/CD nanoparticles might represent an interesting technological platform for the oral administration of small peptides.

Highly sensitive non-stripping gold nanoparticles-based chemiluminescent detection of DNA hybridization coupled to magnetic beads

We have developed a new nanoparticle (NP)-based chemiluminescent (CL) method for the sensitive detection of DNA hybridization. The "sandwich-type" DNA technique comprises NH(2)-functionalized capture DNA immobilized on magnetic beads that can hybridize with one end of the target DNA. The other end of the target is recognized by a reporter DNA probe labeled with Au NPs on its 3-terminus. The hybridization events were monitored by a simple and direct luminol-AgNO(3) CL reaction with a detection limit of 0.5 pM through a non-stripping Au NPs catalysis. Moreover, the CL reaction of non-stripping Au NPs-luminol-AgNO(3) offers the advantages of being simpler and faster as compared to previous stripping Ag NPs and CuS methods. This simple and easy-to-use technique holds great promise for clinical applications of DNA hybridization.