Release Of Therapeutic Molecules Research Articles

Magnetically triggered release of biologics

ABSTRACTThe development of platforms for the controlled release of therapeutic molecules remains a crucial research focus, as controlled release reduces the frequency of administration, minimizes side effects and improves compliance. However, biological conditions and diseases with a progression that exhibits strong temporal dependence, or those that can result in the evolution of tolerance to the therapeutic during continuous exposure, require the development of sophisticated release systems tailored to the needs to the individual and the disease. Thus, there has been emphasis on the development of platforms with remotely controlled release mechanisms. Specifically, magnetically triggered release utilizes magnetic nanoparticles as the remote control modality. Many reviews discuss the magnetically triggered release of small molecule drugs, however, the release of biomacromolecules has not been reviewed. This review examines the limited work on the magnetically triggered release of biomacromolecules and the challenges associated with their delivery. Important material parameters that have been used in this pursuit are discussed.

Near-infrared light for on-demand drug delivery

There are currently many basic technologies for the controlled release of therapeutic molecules for the treatment of chronic pathologies such as arthritis, asthma, and diabetes. Examples of such technologies include selectively dissolvable capsules and tablets that are designed to respond to specific stimuli – such as pH, temperature, or specific enzymes – in a time-specific fashion. However, because of the biological variations between different individuals, which contribute to differences in the environments of therapeutic target locations, these technologies are not fully controllable. In the pursuit of drug-release technologies that are fully controllable, many approaches have been examined. One such approach involves the utilization of various light-sensitive molecules that are designed to release therapeutic agents when stimulated by light of specific wavelengths. Potential light sources that have been explored for this approach include ultraviolet (UV) and near-infrared (NIR) light. UV light, which exists in the range of 10–400 nm, is easily to utilize, and many chemicals and particles can be stimulated with light in this spectrum. Unfortunately, when used extensively – as would be the case for chronic pathologies – UV light can cause cellular damage at the molecular level, potentially leading to skin cancer. A viable alternative to UV light is NIR light, which offers deeper transdermal penetration and does not have many known adverse long-term side effects. Therefore, the purpose of this review is to investigate the use of NIR light and the associated therapeutic molecules for the controlled release of therapeutic agents in the potential treatment of chronic pathologies.

Advanced drug delivery via self-assembled monolayer-coated nanoparticles

Nanotechnology has greatly enhanced the field of medicine over the last decade. Within this field, advances in nanoparticle research have rendered them attractive candidates for drug delivery. Consequently, controlling the chemistry that occurs at the nanoparticle interface influences the efficiency of the drug-delivery system. In this review, we explore the role of coating materials, in the form of self-assembled monolayers (SAMs), in enhancing the interfacial properties of nanoparticles. We discuss how SAMs enhance the properties of particles, such as stability and dispersibility, as well as provide a platform for delivering biomolecules and other therapeutic agents. In addition, we describe recent methods for generating nanoparticles with targeted surface functionality using custom-designed SAMs. These functionalities offer marked advances to the three stages of a drug-delivery system: loading, delivery, and release of therapeutic molecules. A suitable functionalization strategy can provide a means for covalent or non-covalent immobilization of drug molecules. Moreover, a robust coating layer can aid the encapsulation of drug molecules and inhibit molecular degradation during the delivery process. A stimuli-responsive SAM layer can also provide an efficient release mechanism. Thus, we also review how stimuli-responsive coatings allow for the controlled release of therapeutic agents. In addition, we discuss the merits and limitations of stimuli-responsive SAMs as well as possible strategies for future delivery systems. Overall, advances in this research area allow for developing novel drug delivery methodologies with high efficiency and minimal toxicity.

Application of Synthetic Biology to Regenerative Medicine

Synthetic biology uses interchangeable and standardized “bio-parts” to construct complex genetic networks that include sensing, information processing and effector modules: these allow robust and tunable transgene expression in response to a change in signal input. The rise of this field has coincided closely with the emergence of regenerative medicine as a distinct discipline. Unlike synthetic biology, regenerative medicine uses the natural abilities of cells to make trophic factors and to produce new tissues as they would in normal development and tissue maintenance. In this article, we argue that bringing these young fields together, so that synthetic biology techniques are applied to the problem of regeneration, has the potential significantly to enhance our ability to help those in clinical need. We first review the synthetic tool kit available for engineered mammalian networks, then examine the main areas in which synthetic biology techniques might be applied to promote regeneration: (i) biosynthesis and controlled release of therapeutic molecules, (ii) synthesis of scaffold material, (iii) regulation of stem cells, and (iv) programming cells to organize themselves into novel tissues. We finally consider the long-term potential of synthetic biology for regenerative medicine, and the risks and challenges ahead.

Induced Death of Escherichia coli Encapsulated in a Hollow Fiber Membrane as Observed In Vitro or After Subcutaneous Implantation

The encapsulation of bacteria may be used to harness them for longer period of time in order to make them viable, while antibiotic treatment would result in controlled release of therapeutic molecules. Encapsulated bacteria Escherichia coli GFP (green fluorescent protein) (E. coli GFP) were used here as a model for therapeutic substance - GFP fragments release (model of bioactive substances). Our aim was to evaluate the performance of bacteria encapsulated in hollow fibers (HF) treated with antibiotic for induction of cell death. The polypropylene surface modified HF was applied for E. coli encapsulation. The encapsulated bacteria were treated with tetracycline in vitro or in vivo during subcutaneous implantation into mice. The HF content was evaluated in flow cytometer, to assess the bacteria cell membrane permeability changes induced by tetracycline treatment. It was observed that applied membranes prevent release of bacteria through the HF wall. The encapsulated in HF E. coli GFP culture in vitro proves the tetracycline impact on bacteria viability and allows recognition sequence of events within process of bacteria death. Treatment with tetracycline of the SCID mice for 8 hours proves the tetracycline impact on bacteria viability in vivo, rising the necrotic bacteria releasing GFP fragments. It was concluded, that the bacteria may be safely enclosed within the HF at site of implantation, and when the animal is treated with antibiotic bacteria may act as a local source of bioactive factor.

Nanoscale double emulsions stabilized by single-component block copolypeptides

Water-in-oil-in-water emulsions are examples of double emulsions, in which dispersions of small water droplets within larger oil droplets are themselves dispersed in a continuous aqueous phase. Emulsions occur in many forms of processing and are used extensively by the foods, cosmetics and coatings industries. Because of their compartmentalized internal structure, double emulsions can provide advantages over simple oil-in-water emulsions for encapsulation, such as the ability to carry both polar and non-polar cargos, and improved control over release of therapeutic molecules. The preparation of double emulsions typically requires mixtures of surfactants for stability; the formation of double nanoemulsions, where both inner and outer droplets are under 100 nm, has not yet been achieved. Here we show that water-in-oil-in-water double emulsions can be prepared in a simple process and stabilized over many months using single-component, synthetic amphiphilic diblock copolypeptide surfactants. These surfactants even stabilize droplets subjected to extreme flow, leading to direct, mass production of robust double nanoemulsions that are amenable to nanostructured encapsulation applications in foods, cosmetics and drug delivery.

Digestive enzyme targeted polymer therapeutic: MIT WO2007103364

The basic claims of this application involve methods that use a polymer to deliver therapeutic molecules in a targeted fashion using a polymeric carrier, drug and a biologically degradable linker. The release of therapeutic molecule is in response to digestive enzymes that are overexpressed in diseased tissues in the body. Further claims, of the sixteen included, define the digestive enzymes and drug–polymer linkages that may be used and specify tumors as the disease of particular interest. Preclinical examples presented support the idea that this therapeutic design has merit. There does not seem to have a single clinical candidate but future work is expected to develop these molecules into clinical products for cancer and particularly cancer treatment combined with radiation.