Alginate and alginate composites for biomedical applications

Alginate is an edible heteropolysaccharide that abundantly available in the brown seaweed and the capsule of bacteria such as Azotobacter sp. and Pseudomonas sp. Owing to alginate gel forming capability, it is widely used in food, textile and paper industries; and to a lesser extent in biomedical applications as biomaterial to promote wound healing and tissue regeneration. This is evident from the rising use of alginate-based dressing for heavily exuding wound and their mass availability in the market nowadays. However, alginate also has limitation. When in contact with physiological environment, alginate could gelate into softer structure, consequently limits its potential in the soft tissue regeneration and becomes inappropriate for the usage related to load bearing body parts. To cater this problem, wide range of materials have been added to alginate structure, producing sturdy composite materials. For instance, the incorporation of adhesive peptide and natural polymer or synthetic polymer to alginate moieties creates an improved composite material, which not only possesses better mechanical properties compared to native alginate, but also grants additional healing capability and promote better tissue regeneration. In addition, drug release kinetic and cell viability can be further improved when alginate composite is used as encapsulating agent. In this review, preparation of alginate and alginate composite in various forms (fibre, bead, hydrogel, and 3D-printed matrices) used for biomedical application is described first, followed by the discussion of latest trend related to alginate composite utilization in wound dressing, drug delivery, and tissue engineering applications.     

Fast-responsive porous thermoresponsive microspheres for controlled delivery of macromolecules

Porous thermoresponsive microspheres with a homogeneous dimension and distribution of the pores are synthesized by an original method. Poly(N-isopropylacrylamide-co-acrylamide) (poly(NIPAAm-co-AAm)) copolymer was obtained as a thermoresponsive material with a lower critical solution temperature (LCST) under physiologic-like conditions (i.e., at 37 °C and pH 7.4, 50 mM phosphate buffer). Semitelechelic oligomers of NIPAAm (ONIPAAm) were also synthesized in the presence of 3-mercaptopropionic acid (MPA) (chain transfer molecule) which acts as a pore-forming agent. Poly(NIPAAm-co-AAm) and ONIPAAm were solubilized in acidified aqueous solution, dispersed in a mineral oil, and transformed in stable microspheres by crosslinking the amide group with glutaraldehyde at temperatures below and above the LCST of the oligomers, and always below the LCST of the polymer. Microspheres obtained at temperatures below the LCST of ONIPAAm are characterized by a homogeneous porous structure with a narrow distribution of the pore size. These microspheres are characterized by a very rapid response rate when the temperature changes below and above the body temperature. The higher is the amount of the porogen in the polymer solution, the larger is the pore size and faster is the response rate. The porous microspheres with suitable pore size are a conveyable matrix for loading and temperature-controlled release of the high molecular weight model drug blue dextran (BD).     

Bacterial biopolymers: From production to applications in biomedicine

Bacterial polymers obtained tremendous attention over the decades owing to its widespread use in biomedical applications. A better understanding on metabolic pathways and development of improved production strategies through metabolic engineering tools to synthesize tailor made polymer materials to meet their applicability in biomedicine. This review focuses on wide range of these biocompatible polymeric materials include polysaccharides, polyesters, polyamides and polyphosphates with wound healing, antioxidant, antitumor, antimicrobial activities. This review focuses on the advantages of various biomaterials to obtain controlled/sustained drug release and tissue engineering applications in biomedical field and the applications of microbial polysaccharides as drugs in pharmaceutical industry. This review describes the most prominent biomedical applications of bacterial biopolymer material as wound healing bandages, drug delivery, tissue engineering, ortho-dental applications and hydrogels. Reviews the future aspects based on economic feasibility and challenges in mass production and downstream processing of biopolymers and its tailor made synthesis to accomplish diverse applications.     

Phototriggered structures: Latest advances in biomedical applications

Non-invasive control of the drug molecules accessibility is a key issue in improving diagnostic and therapeutic procedures. Some studies have explored the spatiotemporal control by light as a peripheral stimulus. Phototriggered drug delivery systems (PTDDSs) have received interest in the past decade among biological researchers due to their capability the control drug release. To this end, a wide range of phototrigger molecular structures participated in the DDSs to serve additional efficiency and a high-conversion release of active fragments under light irradiation. Up to now, several categories of PTDDSs have been extended to upgrade the performance of controlled delivery of therapeutic agents based on well-known phototrigger molecular structures like o-nitrobenzyl, coumarinyl, anthracenyl, quinolinyl, o-hydroxycinnamate and hydroxyphenacyl, where either of one endows an exclusive feature and distinct mechanistic approach. This review conveys the design, photochemical properties and essential mechanism of the most important phototriggered structures for the release of single and dual (similar or different) active molecules that have the ability to quickly reason of the large variety of dynamic biological phenomena for biomedical applications like photo-regulated drug release, synergistic outcomes, real-time monitoring, and biocompatibility potential.     

Hydrogels in ophthalmic applications

More and more people worldwide are affected by severe eye diseases eventually leading to visual impairment or blindness. In most cases, the treatment involves the application of ophthalmic dosage forms such as eye drops, suspensions or ointments. Unfortunately, some of the therapeutic approaches have major shortcomings, especially in the treatment of the posterior segment of the eye, where many vision-threatening diseases originate. Therefore, research focuses on the development of new materials (e.g., for vitreous substitution) and more advanced drug delivery systems. Hydrogels are an extremely versatile class of materials with many potential applications in ophthalmology. They found widespread application as soft contact lenses, foldable intraocular lenses, in situ gelling formulations for ophthalmic drug delivery and ocular adhesives for wound repair; their use as vitreous substitutes and intravitreal drug delivery systems is currently under investigation. In this article, we review the different applications of hydrogels in ophthalmology with special emphasis placed on the used polymers and their suitability as ocular drug delivery systems.     

Significance of release technology in tissue engineering

Regenerative medical therapy has been expected to compensate for the therapeutic disadvantages of reconstructive surgery and organ transplantation, as well as offering a new therapeutic strategy. The objective of regenerative medical therapy is to induce the repair of defective tissues based on the natural healing potential of patients. For successful tissue regeneration, it is indispensable to provide cells with a local environment of artificial extracellular matrix where they can proliferate and differentiate efficiently. Tissue engineering is the key to this regeneration environment; release technology often enhances the in vivo stability of growth factors and related genes and prolongs the maintenance of biological functions for tissue regeneration.     

Electrohydrodynamics: A facile technique to fabricate drug delivery systems

Electrospinning and electrospraying are facile electrohydrodynamic fabrication methods that can generate drug delivery systems (DDS) through a one-step process. The nanostructured fiber and particle morphologies produced by these techniques offer tunable release kinetics applicable to diverse biomedical applications. Coaxial electrospinning/electrospraying, a relatively new technique of fabricating core-shell fibers/particles have added to the versatility of these DDS by affording a near zero-order drug release kinetics, dampening of burst release, and applicability to a wider range of bioactive agents. Controllable electrospinning/spraying of fibers and particles and subsequent drug release from these chiefly polymeric vehicles depends on well-defined solution and process parameters. The additional drug delivery capability from electrospun fibers can further enhance the material's functionality in tissue engineering applications. This review discusses the state-of-the-art of using electrohydrodynamic technique to generate nanofiber/particles as drug delivery devices.     

Controlled polymorphic transformation of continuously crystallized solid lipid nanoparticles in a microstructured device: A feasibility study

The contribution describes the transfer from a batch to a micro-continuous process for the production of stable solid lipid nanoparticles as drug carrier systems. Solid lipid nanoparticles are commonly prepared batch-wise often resulting in poorly defined product qualities with regard to the polymorphic state of their lipid matrix. In order to obtain solid lipid nanoparticle dispersions that meet the requirements for an acceptable pharmaceutical product, the manufacture of reproducible product qualities preferably containing the stable crystal form of the respective matrix lipid is necessary. These requests are addressed by the continuous preparation process of solid lipid nanoparticles. A four step feasibility study for the standardized evaluation whether or not a colloidal lipid dispersion is suitable for continuous crystallization of the particles resulting in stable crystal forms is presented. The process is based on the continuous crystallization and subsequent thermal treatment of differently stabilized, tripalmitin-based nanoparticle formulations in microstructured devices. The successful production of the stable crystal form by means of a continuous process chain is shown for a dispersion stabilized with a blend of hydrogenated soybean lecithin and sodium glycocholate.     

Studies on thermoresponsive polymers: Phase behaviour,drug delivery and biomedical applications

The present review aims to highlight the applications of thermoresponsive polymers. Thermo-responsive polymers show a sharp change in properties upon a small or modest change in temperature. This behaviour can be utilized for the preparation of so-called ‘smart’ drug delivery systems, which mimic biological response behaviour to a certain extent. Such materials are used in the development of several applications, such as drug delivery systems, tissue engineering scaffolds and gene delivery. Advances in this field are particularly relevant to applications in the areas of regenerative medicine and drug delivery. This review addresses summary of the main applications of thermoresponsive polymers which are categorized based on their 3-dimensional structure; hydrogels, interpenetrating networks, micelles, films and particles. The physico-chemical behaviour underlying the phase transition is also discussed in brief.     

The biology,function, and applications of exosomes in cancer

Exosomes are cell-derived nanovesicles with diameters from 30 to 150 nm, released upon fusion of multivesicular bodies with the cell surface. They can transport nucleic acids, proteins, and lipids for intercellular communication and activate signaling pathways in target cells. In cancers, exosomes may participate in growth and metastasis of tumors by regulating the immune response, blocking the epithelial–mesenchymal transition, and promoting angiogenesis. They are also involved in the development of resistance to chemotherapeutic drugs. Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers. Because of their amphipathic structure, exosomes are natural drug delivery vehicles for cancer therapy.     

PROTAC technology: A new drug design for chemical biology with many challenges in drug discovery

Target Protein Degradation TPD is a new avenue and revolutionary for therapeutics because redefining the principles of classical drug discovery and guided by event-based target activity rather than the occupancy-driven activity. Since the discovery of the first PROTAC in 2001, TPD represents a rapidly growing technology, with applications in both drug discovery and chemical biology. Over the last decade, many questions have been raised and today the knowledge gained by each team has elucidated a number of them, although there is still a long way to go. The objective of this work is to present the challenges that the PROTAC strategy has very recently addressed in drug design and discovery by presenting extremely recent results from the literature and to provide guidelines in the drug design of new PROTACs as successful therapeutic modality for medicinal chemists.     

Laponite®: A key nanoplatform for biomedical applications?

Laponite® is a synthetic smectite clay that already has many important technological applications, which go beyond the conventional uses of clays in pharmaceutics and cosmetics. In biomedical applications, particularly in nanomedicine, this material holds great potential. Laponite® is a 2-dimensional (2D) nanomaterial composed of disk-shaped nanoscale crystals that have a high aspect ratio. These disks can strongly interact with many types of chemical entities (from small molecules or ions, to natural or synthetic polymers, to different inorganic nanoparticles) and are also easily functionalized and readily degraded in the physiological environment giving rise to non-toxic and even bioactive products. This review will highlight the potential of Laponite® as a nanomaterial in the fields of drug delivery, bioimaging, tissue engineering and regenerative medicine. New concepts, as well as novel innovative materials that stand out from the usual ones due to the unique properties of Laponite®, will also be presented and discussed.     

Recent advances in developing polymeric micelles for treating cancer: Breakthroughs and bottlenecks in their clinical translation

Polymeric micelles (PMs) have been explored pre-clinically for the delivery of chemotherapeutics to treat cancer. Their unique features, such as easy surface functionalization, stimuli-responsiveness, good stability, ability to modify drug release, enhanced permeation and retention effect, and potential to encapsulate more than one type of therapeutic molecules at a time, make them unique carriers for the targeted delivery or for enhancing the bioavailability of chemotherapeutics. PMs can also be used as theranostic nanocarriers for the mapping of drug therapy along with tumor imaging in patients with cancer. This review focuses on the limitations of existing treatment strategies and on innovative approaches employed for the functionalization of PMs for targeting cancer cells. In addition, the bottlenecks associated with the translation of PMs from the laboratory to clinics are also discussed.