Maya Davidovich-Pinhas

Evaluating the mucoadhesive properties of drug delivery systems based on hydrated thiolated alginate.

Mucoadhesive polymers have been proposed as drug delivery carriers due to their ability to adhere to the mucus layer. A relatively new class of mucoadhesive polymers, termed thiomers, was suggested as an improved carrier capable of creating disulfide covalent bond with the mucus. Since the wet physiological environment is likely to cause any delivery system to adsorb water and arrive hydrated to its target, studying the performance of mucoadhesive systems in their hydrated form is of major importance. Model thiomer, alginate-thiol, were synthesized and characterized the product using Nuclear Magnetic Resonance (NMR), Fourier Transform Infra Red spectroscopy (FTIR). The swelling behavior was determined gravimetrically and found to be affected from the thiolation. Interactions between the alginate-thiol and mucin glycoproteins, which are believed to be an outcome of disulfide bonds, were verified using rheology experiments. Adhesion of hydrated tablets with different cross linking densities to porcines fresh small intestine tissue were characterized using a Lloyd Tensile Machine. It was shown that the thiolation did not improve the adhesion properties of hydrated tablets. It appears that the benefit achieved by adding thiol group to the polymer in dry tablet form was flawed in hydrated form due to formation of inter-molecular disulfide junctions.

Mucoadhesion: a review of characterization techniques

Importance of the field: Mucoadhesive drug delivery vehicles attract much attention owing to benefits such as extended residence time of the drug at the site of application, a relatively rapid uptake of a drug into the systemic circulation, and enhanced bioavailability of therapeutic agents. Mucoadhesion, defined as the ability to adhere to the mucus gel layer covering organs that are exposed to the outer surface of the body yet are not covered with skin, such as the mouth and the respiratory tract, is a key element in the design of these drug delivery systems. Areas covered in this review: This review focuses on the numerous experimental methods that have been proposed over the years for mucoadhesion characterization. These techniques are categorized into directs methods, which measure the force or time required to detach the mocoadhesive from a mucus, and indirect methods, which asses the interactions between the mucoadhesive and mucin type glycoproteins. What the reader will gain: The comprehensive description of the available techniques could facilitate the selection of a characterization method that meets the requirements of a specific study. Moreover, a comparison between the results obtained in different laboratories is given whenever possible. Take home message: The challenge of adopting a universal test method that could be used to compare data from different research groups and rank new mucoadhesion candidates has not yet been met.

Alginate-PEGAc: a new mucoadhesive polymer.

We have synthesized a novel mucoadhesive polymer, alginate-polyethylenglycol acrylate (alginate-PEGAc), in which an alginate backbone carries acrylated polyethylenglycol. This polymer combines the strength, simplicity and gelation ability of alginate with the mucoadhesion properties arising from the characteristics and acrylate functionality of PEG. The strong bonding to the mucus results from a combination of PEGs ability to interpenetrate the mucus surface and a Michael-type addition reaction between an acrylate end group on a polymer and the sulfide end group of the mucin-type glycoprotein. We have synthesized alginate-PEGAc, verified the formation of the desired product by nuclear magnetic resonance, demonstrated the lack of cytotoxicity, and evaluated the ability of this polymer to function as a novel mucoadhesive material for controlled drug release. Based on our findings we believe that modifying other polymers with PEG-acrylate can open the way for the development of many other multifunctional biomaterials for a variety of biotechnological and biomedical applications.

Novel mucoadhesive system based on sulfhydryl-acrylate interactions

We propose a novel cross-linked mucoadhesive system that can interact covalently with mucin type glycoprotein, thus providing both strong bonding to mucosa as well as ability to function as a sustained release matrix. The strong bonding results from Michael type addition reaction between an acrylate end group on a polymer and the sulfide end group of the mucin type glycoprotein. A proof of concept is provided using a polyehtylene glycol hydrogel formed in situ from polyehtylene glycol di-acrylate (PEG-DA) macromers. The ability of PEG-DA to create interactions with mucin type glycoproteins was verified using nuclear magnetic resonance (NMR) and rheology experiments. NMR studies have detected disappearance of the PEG-DA’s vinyl protons upon mucin addition, whereas rheology measurements have shown a viscosity increase. These results provide an evidence for the formation of mucin-polymer covalent bond. The ability PEG-DA to attach to mucus and promote mucoadhesion was evaluated by tensile measurements. PEG-DA adhered at strength comparable to other covalently interacting mucoadhesive polymers. Furthermore, PEG-DA was found to be a suitable candidate for sustained release of the hydrophilic drug Ibuprofen.

Development, Characterization, and Utilization of Food-Grade Polymer Oleogels

The potential of organogels (oleogels) for oil structuring has been identified and investigated extensively using different gelator-oil systems in recent years. This review provides a comprehensive summary of all oil-structuring systems found in the literature, with an emphasis on ethyl-cellulose (EC), the only direct food-grade polymer oleogelator. EC is a semicrystalline material that undergoes a thermoreversible sol-gel transition in the presence of liquid oil. This unique behavior is based on the polymers ability to associate through physical bonds. These interactions are strongly affected by external fields such as shear and temperature, as well as by solvent chemistry, which in turn strongly affect final gel properties. Recently, EC-based oleogels have been used as a replacement for fats in foods, as heat-resistance agents in chocolate, as oil-binding agents in bakery products, and as the basis for cosmetic pastes. Understanding the characteristics of the EC oleogel is essential for the development of new applications.

Drug Delivery Systems Based On Mucoadhesive Polymers

Transmucosal delivery of therapeutic agents is a non-invasive approach that utilizes human entry paths such as the nasal, buccal, rectal and vaginal routs. Mucoadhesive polymers have the ability to adhere to the mucus layer covering those surfaces and by that promote drug release, targeting and absorption. Mucoadhesive polymers commonly interact with mucus through non-covalent bonds such as hydrogen bonds, ionic interactions and/or chain entanglement. This chapter reviews variety of mucoadhesive polymeric systems with a special emphasis on recent developments in the field. In particular, a new class of covalently interacting mucoadhesive polymers termed acrylated mucoadhesive polymers is described in detail. Acrylated mucoadhesive polymers are macromolecules which carry at least one double bond therefore are capable of forming covalent link with thiol groups on mucin type glycoproteins, the main component of mucus. To date, two acrylated mucoadhesive polymers were synthesized, and their ability to act as a mucoadhesive drug release vehicle was characterized and compare to other covalently binding mucoadhesive polymers. This approach opens a way to additional clinical applications that will benefit from the administration of drugs through the mucosa surface.