Effect of nanoparticle size on their distribution and retention in chronic inflammation sites.

Nanomedicines are increasingly researched and used for the treatment of chronic inflammatory diseases. Herein, the effect of the size of nanoparticles on their distribution and retention in chronic inflammatory sites, as compared to healthy tissues, was studied in a mouse model with chronic inflammation in one of the hind footpads. Using PEGylated gold nanoparticles of 2, 10, 100, and 200 nm, we found that although the smaller nanoparticles of 2 and 10 nm showed greater distribution and slower clearance in the inflamed footpad than the relatively larger nanoparticles of 100 and 200 nm, the larger nanoparticles of 100 and 200 nm were more selectively distributed in the inflamed hind footpad than in the healthy hind footpad in the same mouse.

Dry powders for inhalation containing monoclonal antibodies made by thin-film freeze-drying.

Thin-film freeze-drying (TFFD) is a rapid freezing and then drying technique used to prepare inhalable dry powders from the liquid form for applications such as drug delivery to the lungs. Herein we report the preparation of aerosolizable dry powders of monoclonal antibodies (mAbs) by TFFD. We first formulated an IgG antibody with lactose/leucine (60:40, w/w) or trehalose/leucine (75:25) and tested their aerosol performance.

4-(N)-Docosahexaenoyl 2', 2'-difluorodeoxycytidine induces immunogenic cell death in colon and pancreatic carcinoma models as a single agent.

Purpose: Docosahexaenoyl difluorodeoxycytidine (DHA-dFdC) is an amide with potent, broad-spectrum antitumor activity. In the present study, DHA-dFdC's ability to induce immunogenic cell death (ICD) was tested using CT26 mouse colorectal cancer cells, an established cell line commonly used for identifying ICD inducers, as well as Panc-02 mouse pancreatic cancer cells.

Methods: The three primary surrogate markers of ICD (i.

Intranasal vaccine: Factors to consider in research and development.

Most existing vaccines for human use are administered by needle-based injection. Administering vaccines needle-free intranasally has numerous advantages over by needle-based injection, but there are only a few intranasal vaccines that are currently approved for human use, and all of them are live attenuated influenza virus vaccines. Clearly, there are immunological as well as non-immunological challenges that prevent vaccine developers from choosing the intranasal route of administration.

PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth : PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles.

The present study was designed to test the hypothesis that programmed cell death-1 (PD-1) siRNA can downregulate PD-1 expression in macrophages in culture and in tumor tissues in mice and inhibit tumor growth in a mouse model. PD-1 siRNA was encapsulated in solid lipid nanoparticles (SLNs), and the physical properties of the resultant SLNs were characterized. The ability of the PD-1 siRNA-SLNs to downregulate PD-1 expression was confirmed in J774A.

Gap Junction Liposomes for Efficient Delivery of Chemotherapeutics to Solid Tumors.

Chemotherapeutic delivery is limited by inefficient transport across cellular membranes. Here, we harness the cellular gap junction network to release therapeutic cargos directly into the cytosol. Specifically, cell-derived vesicles, termed connectosomes, contain gap junction transmembrane proteins that open a direct passageway to the cellular interior.

Rationally Designed Redox-Active Au(I) N-Heterocyclic Carbene: An Immunogenic Cell Death Inducer.

Immunogenic cell death (ICD) is a way of reengaging the tumor-specific immune system. ICD can be induced by treatment with chemotherapeutics. However, only a limited number of drugs and other treatment modalities have been shown to elicit the biomarker responses characteristic of ICD and to provide an anticancer benefit in vivo.

Effect of the Ratio of Betamethasone to TNF-α siRNA Coencapsulated in Solid Lipid Nanoparticles on the Acute Proinflammatory Activity of the Nanoparticles.

There is evidence that encapsulating glucocorticoids into nucleic acid-containing nanoparticles reduces the inflammatory toxicities of the nanoparticles. Herein, using betamethasone acetate (BA), a glucocorticoid, and a solid lipid nanoparticle formulation of siRNA, we confirmed that coencapsulating BA into the siRNA solid lipid nanoparticles significantly reduced the proinflammatory activity of the siRNA nanoparticles in a mouse model. Using TNF-α siRNA, we then showed that the BA and TNF-α siRNA coencapsulated into the solid lipid nanoparticles acted as a dual anti-inflammatory and synergistically reduced TNF-α release by mouse macrophages in culture following stimulation with lipopolysaccharide, as compared to solid lipid nanoparticles encapsulated with TNF-α siRNA or BA alone.

Zoledronic Acid-containing Nanoparticles With Minimum Premature Release Show Enhanced Activity Against Extraskeletal Tumor.

Bisphosphonates are generally used to treat bone diseases, such as bone metastasis from cancer. There is evidence that, through the modification of the pharmacokinetics and biodistribution of bisphosphonates by formulating them into nanoparticles, they may be able to treat extraskeletal tumors. However, many previously reported bisphosphonate nanoparticle formulations show extensive premature release of bisphosphonates.

Aluminum (Oxy)Hydroxide Nanosticks Synthesized in Bicontinuous Reverse Microemulsion Have Potent Vaccine Adjuvant Activity.

Insoluble aluminum salts such as aluminum (oxy)hydroxide are commonly used as vaccine adjuvants. Recently, there is evidence suggesting that the adjuvant activity of aluminum salt-based materials is tightly related to their physicochemical properties, including nanometer-scale size, shape with long aspect ratio, and low degree of crystallinity. Herein, for the first time, the bicontinuous reverse microemulsion (RM) technique was utilized to synthesize stick-like monodisperse aluminum (oxy)hydroxide nanoparticles with a long aspect ratio of ∼10, length of ∼80 nm, and low degree of crystallinity (denoted as Al-nanosticks).

Reverse Microemulsion-Based Synthesis of (Bis)phosphonate-Metal Materials with Controllable Physical Properties: An Example Using Zoledronic Acid-Calcium Complexes.

The development of phosphonate-metal materials is tightly related to the advancement in their synthesis methods. Herein, using zoledronic acid (Zol), a bisphosphonate (bioacitve phosphonate with a "P-C-P" structure), and calcium as model molecules, we applied the reverse microemulsion (RM) method to synthesize a series of Zol-Ca complexes. We comprehensively (i) studied the relationship between RM conditions, including the component ratio of RM, cosurfactants, reaction time, reactant concentration, reaction temperature, and the presence of a phospholipid, 1, 2-dioleoyl-sn-glycero-3-phosphate acid (DOPA), and the physical properties of the complexes synthesized (i.