Smart pills and drug delivery devices enabling next generation oral dosage forms.

Oral dosage forms are the preferred solution for systemic treatment and prevention of disease conditions. However, traditional dosage forms face challenges regarding treatment adherence and delivery of biologics. Oral therapies that require frequent administrations face difficulties with patient compliance.

Fully Biodegradable Elastomer-Based Device for Oral Macromolecule Delivery.

Oral devices, such as foil-type devices, show great potential for the delivery of poorly permeable macromolecules by enabling unidirectional release of the loaded pharmaceutical composition in close proximity to the epithelium in the small intestine or colon. However, one of the primary concerns associated with the use of foil-type devices so far has been the utilization of nonbiodegradable elastomers in the fabrication of the devices. Therefore, research into biodegradable substitute materials with similar characteristics enables drug delivery in a sustainable and environmentally friendly manner.

Flexible Coatings Facilitate pH-Targeted Drug Release via Self-Unfolding Foils: Applications for Oral Drug Delivery.

Ingestible self-configurable proximity-enabling devices have been developed as a non-invasive platform to improve the bioavailability of drug compounds via swellable or self-unfolding devices. Self-unfolding foils support unidirectional drug release in close proximity to the intestinal epithelium, the main drug absorption site following oral administration. The foils are loaded with a solid-state formulation containing the active pharmaceutical ingredient and then coated and rolled into enteric capsules.

Magnetic and/or Radiopaque Functionalization of Self-Unfolding Foils for Improved Applicability within Oral Drug Delivery.

Various types of microfabricated devices have been proposed for overcoming the gastrointestinal (GI) challenges associated with oral administration of pharmaceutical compounds. However, unidirectional drug release in very close forced proximity to the intestinal wall still appears to be an unresolved issue for many of these microdevices, which typically show low drug absorption and thereby low bioavailabilities. This work explores how recently developed and promising self-unfolding foils (SUFs) can be magnetically and/or radiopaquely (M/R-) functionalized, by the addition of BaSO or FeO nanoparticles, for improving their applicability within oral drug delivery.

A self-unfolding proximity enabling device for oral delivery of macromolecules.

Oral delivery of macromolecules remains highly challenging due to their rapid degradation in the gastrointestinal tract and poor absorption across the tight junctions of the epithelium. In the last decade, researchers have investigated several medical devices to overcome these challenges using various approaches, some of which involve piercing through the intestine using micro and macro needles. We have developed a new generation of medical devices called self-unfolding proximity enabling devices, which makes it possible to orally deliver macromolecules without perforating the intestine.

Microscopic Cascading Devices for Boosting Mucus Penetration in Oral Drug Delivery-Micromotors Nesting Inside Microcontainers.

In the case of macromolecules and poorly permeable drugs, oral drug delivery features low bioavailability and low absorption across the intestinal wall. Intestinal absorption can be improved if the drug formulation could be transported close to the epithelium. To achieve this, a cascade delivery device comprising Magnesium-based Janus micromotors (MMs) nesting inside a microscale containers (MCs) has been conceptualized.

In Vitro Cellular Delivery of Peptide Nucleic Acid (PNA).

Cellular delivery methods are a prerequisite for cellular studies with PNA. This chapter describes PNA cellular delivery using cell-penetrating peptide (CPP)-PNA conjugates and transfection of PNA-ligand conjugates mediated by cationic lipids. Furthermore, two endosomolytic procedures employing chloroquine treatment or photochemical internalization (PCI) for significantly improving PNA delivery efficacy are described.

Enzyme-Triggered Release of the Antisense Octaarginine-PNA Conjugate from Phospholipase A2 Sensitive Liposomes.

Phospholipase sensitive liposomes (PSLs) have attracted great attention in targeted anticancer drug delivery due to cargo release triggered by tumor-secreted phospholipase A (sPLA). Such liposomes could also serve as a vehicle for tissue-specific delivery of antisense therapeutics to (solid) tumors. While extensive studies on developing PSL formulations for small molecules exist, hardly any data are available on delivering larger molecules such as antisense agents.

Impact of plasma concentration of transferrin on targeting capacity of nanoparticles.

It is becoming increasingly accepted that various diseases have a capacity to alter the composition of plasma proteins. This alteration in protein composition may consequently change the targeting capacity of nanoparticles (NPs). In this study, the impact of a model targeting ligand's (i.

Cooperative Cellular Uptake and Activity of Octaarginine Antisense Peptide Nucleic acid (PNA) Conjugates.

Cellular uptake and antisense activity of d-octaarginine conjugated peptide nucleic acids (PNAs) is shown to exhibit pronounced cooperativity in serum-containing medium, in particular by being enhanced by analogous mis-match PNA-cell-penetrating peptide (PNA-CPP) conjugates without inherent antisense activity. This cooperativity does not show cell or PNA sequence dependency, suggesting that it is a common effect in cationic CPP conjugated PNA delivery. Interestingly, our results also indicate that Deca-r8-PNA and r8-PNA could assist each other and even other non-CPP PNAs as an uptake enhancer agent.

One-pot synthesis and characterization of ovalbumin-conjugated gold nanoparticles: A comparative study of adjuvanticity against the physical mixture of ovalbumin and gold nanoparticles.

Only few adjuvants are licensed for use in humans and there is a need to develop safe and improved vaccine adjuvants. In this study, we report the one-pot synthesis of antigen ovalbumin (OVA)-conjugated gold nanoparticles (OVA@GNPs). A systematical study was performed by comparing OVA@GNPs with the simple mixture of OVA and gold nanoparticles (OVA+GNPs), including their physiochemical properties through spectrometric and electrophoretic analysis, in vitro stability, cytotoxicity and cellular uptake, and in vivo humoral immune responses following subcutaneous and transcutaneous immunization in mice.

Theranostic MUC-1 aptamer targeted gold coated superparamagnetic iron oxide nanoparticles for magnetic resonance imaging and photothermal therapy of colon cancer.

Favorable physiochemical properties and the capability to accommodate targeting moieties make superparamegnetic iron oxide nanoparticles (SPIONs) popular theranostic agents. In this study, we engineered SPIONs for magnetic resonance imaging (MRI) and photothermal therapy of colon cancer cells. SPIONs were synthesized by microemulsion method and were then coated with gold to reduce their cytotoxicity and to confer photothermal capabilities.

External magnetic fields affect the biological impacts of superparamagnetic iron nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the promising nanomaterials for applications in various field of nanomedicine such as targeted imaging/drug delivery, tissue engineering, hyperthermia, and gene therapy. Besides their suitable biocompatibility, SPIONs' unique magnetic properties make them an outstanding candidate for theranostic nanomedicine. Very recent progress in the field revealed that the presence of external magnetic fields may cause considerable amount of SPIONs' agglomeration in their colloidal suspension.

Protein corona composition of gold nanoparticles/nanorods affects amyloid beta fibrillation process.

Protein fibrillation process (e.g., from amyloid beta (Aβ) and α-synuclein) is the main cause of several catastrophic neurodegenerative diseases such as Alzheimer's and Parkinson diseases.

Monoclonal antibody conjugated magnetic nanoparticles could target MUC-1-positive cells in vitro but not in vivo.

MUC1 antigen is recognized as a high-molecular-weight glycoprotein that is unexpectedly over-expressed in human breast and other carcinomas. In contrast, C595 a monoclonal antibody (mAb) against the protein core of the human urinary epithelial machine, is commonly expressed in breast carcinomas. The aim of this study was to conjugate ultra-small super paramagnetic iron oxide nanoparticles (USPIO) with C595 mAb, in order to detect in vivo MUC1 expression.

Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade hypothesis.

Physiological temperature has a crucial role in amyloid β in the absence and presence of hydrophobic and hydrophilic nanoparticles.

Amyloid beta fibrillation can lead to major disorder of neurons processes and is associated with several neuronal diseases (e.g., Alzheimer's disease).

Graphene oxide strongly inhibits amyloid beta fibrillation.

Unlabelled: Since amyloid beta fibrillation (AβF) plays an important role in the development of neurodegenerative diseases, we investigated the effect of graphene oxide (GO) and their protein-coated surfaces on the kinetics of Aβ fibrillation in the aqueous solution. We showed that GO and their protein-covered surfaces delay the AβF process via adsorption of amyloid monomers. Also, the large available surface of GO sheets can delay the AβF process by adsorption of amyloid monomers.

Bacterial effects and protein corona evaluations: crucial ignored factors in the prediction of bio-efficacy of various forms of silver nanoparticles.

Because of their unique properties which are strongly dependent on the physicochemical properties of metal nanomaterials, noble metal nanostructures, particularly silver, have attracted much attention in the fields of electronics, chemistry, physics, biology, and medicine. Regarding biology and medical applications, silver nanoparticles (NPs) are recognized as a promising candidate to fight against resistant pathogens because of their significant antimicrobial activities. However, there are two major ignored issues with these NPs.