The role of patient-specific variables in protein corona formation and therapeutic efficacy in nanomedicine.

Despite their potential, the adoption of nanotechnology in therapeutics remains limited, with only around eighty nanomedicines approved in the past 30 years. This disparity is partly due to the "one-size-fits-all" approach in medical design, which often overlooks patient-specific variables such as biological sex, genetic ancestry, disease state, environment, and age that influence nanoparticle behavior. Nanoparticles (NPs) must be transported through systemic, microenvironmental, and cellular barriers that vary across heterogeneous patient populations.

siRNA Delivery from Cationic Nanocarriers Prepared by Diffusion-assisted Loading in the Presence and Absence of Electrostatic Interactions.

In this study, we use modified cationic nanocarriers as vehicles for the intracellular delivery of therapeutic siRNA. After developing nanocarrier formulations with appropriate pK, size, swellability, and cytocompatibility, we investigated the importance of siRNA loading methods by studying the impact of the pH and time over which siRNA is loaded into the nanocarriers. We concentrate on diffusion-based loading in the presence and absence of electrostatic interactions.

Design of nanoparticle-based systems for the systemic delivery of chemotherapeutics: Alternative potential routes via sublingual and buccal administration for systemic drug delivery.

Conventional therapeutic approaches for cancer generally involve chemo- and radiation therapies that often exhibit low efficacy and induce toxic side effects. Recent years have seen significant advancements in the use of protein biologics as a promising alternative treatment option. Nanotechnology-based systems have shown great potential in providing more specific and targeted cancer treatments, thus improving upon many of the limitations associated with current treatments.

PEGylated insulin loaded complexation hydrogels for protected oral delivery.

While a number of enteric coatings and pH-sensitive oral delivery vehicles have been developed, they lack the ability to sufficiently protect proteins from proteolytic degradation once released from the carrier. In this work, we show that H-bonded, pH-sensitive poly(methacrylic acid-grafted ethylene glycol) glycol (henceforth designated as P(MAA-g-EG) gels) exhibit great promise as protein carriers, as they utilize poly(ethylene glycol) (PEG) chains to promote mucoadhesion in the small intestine, increasing the chances that the drug is released within the villus of the absorptive intestinal wall. Importantly, PEG was also conjugated to the B29-lysine (LysB29) position of insulin in order to protect the drug from proteolytic degradation once released in the small intestine and adhere the drug to the intestinal epithelium through improved mucoadhesion.

Drug delivery methods for cancer immunotherapy.

Despite the fact that numerous immunotherapy-based drugs have been approved by the FDA for the treatment of primary and metastatic tumors, only a small proportion of the population can benefit from them because of primary and acquired resistances. Moreover, the translation of immunotherapy from the bench to the clinical practice is being challenging because of the short half-lives of the involved molecules, the difficulties to accomplish their delivery to the target sites, and some serious adverse effects that are being associated with these approaches. The emergence of drug delivery vehicles in the field of immunotherapy is helping to overcome these difficulties and limitations and this review describes how, providing some illustrative examples.

Targeted delivery methods for RNA interference are necessary to obtain a potential functional cure for HIV/AIDS.

Ribonucleic acid (RNA) is of great interest in many different therapeutic areas including infectious diseases such as immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Thanks to current, advanced treatments for HIV, the diagnosis is no longer a death sentence. However, even with these treatments, latency is suggested to persist in T-lymphocyte-rich tissues including gut-associated lymphatic tissue (GALT), spleen, and bone marrow making HIV an incurable disease.

Immunotherapy approaches for hematological cancers.

Hematological cancers such as leukemia, lymphoma, and multiple myeloma have traditionally been treated with chemo and radiotherapy approaches. Introduction of immunotherapies for treatment of these diseases has led to patient remissions that would not have been possible with traditional approaches. In this critical review we identify main disease characteristics, symptoms, and current treatment options.

Combining modeling of drug uptake and release of cyclosporine in contact lenses to determine partition coefficient and diffusivity.

Ophthalmic drug delivery via eye drops is inefficient because only about 1-5% of the drug permeates the cornea during the short residence time of a few minutes. Contact lenses are receiving considerable attention for delivering ophthalmic drugs because of higher bioavailability and the possibility of sustained release from hour to days, and possibly longer. The drug release durations from contact lenses are typically measured in vitro and it is challenging to relate the in vitro release to in vivo release, particularly for hydrophobic drugs which may not exhibit sink release in vitro and in vivo.

Review of Approaches for Increasing Ophthalmic Bioavailability for Eye Drop Formulations.

Ophthalmic diseases represent a significant problem as over 2 billion people worldwide suffer from vison impairment and blindness. Eye drops account for around 90% of ophthalmic medications but are limited in success due to poor patient compliance and low bioavailability. Low bioavailability can be attributed to short retention times in the eye caused by rapid tear turnover and the difficulty of drug diffusion through the multi-layered structure of the eye that includes lipid-rich endothelial and epithelial layers as well as the stroma which is high in water content.

Poly (Vinyl Alcohol) Assisted Synthesis and Anti-Solvent Precipitation of Gold Nanoparticles.

Gold nanoparticles (GNPs) are commonly synthesized using the Turkevich method, but there are limitations on the maximum concentration of gold nanoparticles that can be achieved using this method (often < 1 mM (=0.34 mg/mL) gold precursor loading). Here, we report an inverse Turkevich method which significantly increases the concentration of gold nanoparticles (up to 5-fold) in the aqueous phase by introducing poly (vinyl alcohol) (PVA) to the synthesis system for stabilization.

Magnetically Responsive Polymeric Microparticles for the Triggered Delivery of a Complex Mixture of Human Placental Proteins.

Bone loss through traumatic injury is a significant clinical issue. Researchers have created many scaffold types to mimic an extracellular matrix to provide structural support for the formation of new bone, however functional regeneration of larger scaffolds has not been fully achieved. Newer scaffolds aim to deliver bioactive molecules to improve tissue regeneration.

Model of Magnetic Particle Capture Under Physiological Flow Rates for Cytokine Removal During Cardiopulmonary Bypass.

Objective: The objective of this study is to design a physical model of a magnetic filtration system which can separate magnetic nanoparticle (MNP)-tagged cytokines from fluid at physiologically relevant flow rates employed during cardiopulmonary bypass (CPB) procedures.

Methods: The Navier-Stokes equations for the pressure driven flow in the chamber and the quasistatic stray magnetic field produced by an array of permanent magnets were solved using finite element analysis in COMSOL Multiphysics for 2D and 3D representations of the flow chamber. Parameters affecting the drag and magnetic forces including flow chamber dimensions, high gradient magnet array configurations, and particle properties, were changed and evaluated for their effect on MNP capture.

Commercialization challenges for drug eluting contact lenses.

Introduction: Eye drops are commonly used for delivering ophthalmic drugs despite many deficiencies including low bioavailability and poor compliance. Contact lenses can deliver drugs with high bioavailability but commercial contacts release drug rapidly, limiting benefits and necessitating modifications to improve the drug release characteristics.

Areas Covered: This review covers the common approaches to prolong the release rates of drugs from contact lenses including molecular imprinting, incorporation of nano/microparticles, vitamin-E barriers, and layered/implant contact lenses.

Evaluation of magnetic nanoparticles for magnetic fluid hyperthermia.

Magnetic nanoparticles (MNPs) generate heat when exposed to an alternating magnetic field. Consequently, MNPs are used for magnetic fluid hyperthermia (MFH) for cancer treatment, and have been shown to increase the efficacy of chemotherapy and/or radiation treatment in clinical trials. A downfall of current MFH treatment is the inability to deliver sufficient heat to the tumor due to: insufficient amounts of MNPs, unequal distribution of MNPs throughout the tumor, or heat loss to the surrounding environment.

Phenylmethimazole and a thiazole derivative of phenylmethimazole inhibit IL-6 expression by triple negative breast cancer cells.

Inhibition of interleukin-6 (IL-6) holds significant promise as a therapeutic approach for triple negative breast cancer (TNBC). We previously reported that phenylmethimazole (C10) reduces IL-6 expression in several cancer cell lines. We have identified a more potent derivative of C10 termed COB-141.

Simple modifications to methimazole that enhance its inhibitory effect on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression by human endothelial cells.

The expression of vascular cell adhesion molecule-1 (VCAM-1) on the vascular endothelium can be increased by pro-inflammatory cytokines [e.g. tumor necrosis factor-α (TNF-α)].