Current Pharmaceutical Design - Volume 21, Issue 33, 2015

Polysaccharide rich gums and mucilages are produced by different natural sources such as plants, animals and microbial organisms to fulfil structural and physiological functions. Their diverse structural compositions with a broad range of physicochemical properties make them useful for inclusion in dosage forms for different purposes such as to improve manufacturing processes and/or to facilitate drug delivery. A number of natural gums and mucilages have been investigated for inclusion in pharmaceutical formulations for a variety of reasons. The search for new excipients continues to be an active topic in dosage form design and drug delivery research. The aim of this review article is to give an overview of the chemical nature of natural gums and mucilages and to discuss their applications in the formulation of pharmaceutical dosage forms. Special emphasis will be placed on the use of gums and mucilages in novel drug delivery systems, such as modified release dosage forms and delivery systems that target specific sites of delivery.

There has been increased interest in novel drug delivery systems to be administered via mucosal routes as an alternative to the currently used traditional routes such as parenteral (injections) and oral routes of administration. This is due to the several advantages they offer including avoiding first pass metabolism in the liver for oral administration and local activity which avoids the need for high systemic doses. To achieve the foregoing objectives, bioadhesive vehicles are required that ensure prolonged residence time to achieve systemic bioavailability via substantial drug absorption or significant drug concentration for local action. The drug delivery system is also required to be non-deleterious to the site of application and be well tolerated by vulnerable groups such as paediatric and geriatric patients. These essential characteristics are mainly satisfied by naturally occurring polymers, including polysaccharide based polymers which have the advantage of biocompatibility, biodegradability and therefore safety. This review discusses various bioadhesive polymers of polysaccharide origin formulated into a variety of dosage forms for drug delivery via the body’s mucosal (moist) surfaces including ocular, oral (buccal and sublingual), nasal, gastrointestinal and vaginal mucosa, as well as moist wound sites. The anatomy and / or physiology of each site, coupled with the unique challenges each poses, the strategies employed for ensuring therapeutic efficacy, as well as the current state of the art will also be covered.

Cancer disease is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and around 8 million cancer-related deaths yearly. Estimates expect to increase these figures over the next few years. Therefore, it is very important to develop more effective and targeted therapies. Polysaccharides are widely used for biomedical and pharmaceutical applications due to their interesting properties, and can be utilised in the production of nanovehicles for drug delivery, since they frequently extend the half-life and improve the stability of chemotherapeutic agents in bloodstream allowing them to reach the tumour tissue. Moreover, polysaccharide-based nanovehicles are generally expected to increase the therapeutic benefit by reducing the undesired side effects and promoting a more efficient cellular uptake. Here, we highlight the application of various polysaccharides as nanovehicles in cancer therapy, focusing mainly on in vivo applications and describing the main advantages of each designed system in a critical way. The use of different polysaccharides interacting with metal nanoparticles to develop new nanovehicles for cancer therapy will also be discussed.

Polysaccharides belong to a special class of biopolymers that has been used in different areas of research and technology for some years now. They present distinctive features attractive for the biomedical field. Among others, as extracted from natural sources, these materials are usually biocompatible and possess a significant ability to absorb water. Moreover, they can be conveniently modified by chemical means so as to display improved biological and physicochemical properties. The last but not the least, they are abundant in the natural Extracellular Matrix (ECM) and have a tremendous affinity for different endogenous macromolecules. Accordingly, these particular materials constitute outstanding candidates for a variety of biomimetic approaches entailing the entrapment/stabilization of bioactive molecules (e.g. growth factors, siRNA, and DNA) that could be delivered and have an effect on relevant cellular mechanisms, such as gene expression and cell viability, -proliferation, and -differentiation. This review will explore the current status of nano-scale drug delivery devices based on polysaccharides that could be used in tissue engineering and regenerative medicine (TERM). Aiming to contextualize the topics here discussed, especially for non-experts in the field, section 1 (Introduction) will present a brief overview of TERM and the principal polysaccharides herein employed. In order to get a broader perspective on both issues, this section will include a brief description of non-nanometric systems with relevant characteristics for TERM, such as injectable microparticles and macroscopic hydrogels, just to cite a few. Section 2 will illustrate the contributions of nanotechnology to the development of TERM, in particular to the development of biomimetic systems capable of replicating the natural, endogenous ECMs. Next, sections 3 to 6 will describe representative systems in the nanometric scale presenting 0D (nanoparticles), 1D (nanorods and nanowires), 2D (thin coatings/films or multilayered systems), and 3D (woven nanofibrillar mats and meshes) configurations, respectively. Special attention will be paid on how nanometric constructs with these configurations can be used as model systems in TERM to understand and/or manipulate biological functions at the cellular level. Finally, section 7 will provide an outlook on future perspectives in the field. Overall, the review is intended to constitute a critical source of information relative to the current status of polysaccharide- based biomaterials for TERM, in particular those at the nanometric scale.

Obtaining successful ocular formulations able to support an efficient drug concentration at the target tissue for an appropriate period of time is an interesting challenge for modern pharmaceutical technology. In this sense, nanotechnology is one of the available strategies to obtain a drug carrier system that allows access to different compartments of the eye in order to deliver drugs to the desired site. Biodegradable polymers such as polysaccharides are promising biomaterials for the production of biocompatible and biodegradable nanocarriers (NCs). Different types of polysaccharide NCs are capable of improving the transport of drugs after ocular application and they can be either polysaccharide-matrix carriers or polysaccharide-coated carriers, depending on whether polysaccharide is used as a matrix or as a coating, respectively. This review focuses on recent advances achieved by polysaccharide-based NCs for the treatment of ocular disorders.

Infectious diseases are an important health concern, as several pathogens have developed the ability to survive inside phagocytic cells (mostly macrophages), encountered at early infection stages, using these cells as trojan horses. In fact, in several cases macrophages have become a nutrient reservoir that helps pathogens to grow in number and spread. It is frequent that conventional therapeutic schedules include long periods of drug intake, at high doses, in some cases leading to severe side effects and clinical relapses due to prolonged intake, along with an increased risk for the development of antibiotic resistances. Therefore, there is a compelling need to develop new therapeutic strategies providing a targeted drug delivery to macrophages. These cells have unique surface receptors that might recognise preferentially several polysaccharide moieties present on the surface of infecting organisms, including in the bacterial cell wall. Benefiting from a similar composition regarding the referred moieties, polysaccharides might be good candidates to compose the matrix of drug carriers aimed at macrophage targeting, as they can use the same recognition pathways of the infecting organisms. This review describes the features and the role of macrophages in infectious conditions, while addressing their potential as therapeutic targets and unravelling the prominent role of polysaccharides as matrix materials of drug delivery systems developed for the therapy of infectious diseases.

The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) stomach infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharides), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario, geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context, the exploration of the biological activity of plant-derived products or polysaccharides commonly present in foods is increasingly becoming more and more attractive. This review aims to present the current state-of-the-art on the antiadhesive capacity of different polysaccharide families, on polysaccharide-based nanosystems and the proof-of-concept evidence of their potential use as alternative medicines against H. pylori.

Arthritics diseases, such as rheumatoid arthritis and osteoarthritis are chronic inflammatory and one of the most prevalent health conditions that cause disability (pain and functional limitation of joints). Despite the research advances, the treatment of those pathological conditions remains ineffective, since the pharmacological therapy is palliative, reducing only the symptoms and, in some cases, the chronic progression of the disease. In this context, the development of new formulations for controlled release would be interesting for reducing the number of injections and would also increase the patient compliance. In this article, we present a review of the cyclodextrin (CD)-based delivery systems focusing from conventional guest-host inclusion complexes and CD-polysulphates, until supramolecular architectures such as drug-CD-polymers conjugates, pseudorotaxanes, hydrogels as well as double-carrier systems and other systems. In particular, this article focuses the main CD-based delivery systems described in the literature emphasizing their possible administration by intra-articular route on the treatment of arthritic diseases, concentrating on their development and also performance as in vivo experimental therapeutic systems.

Alginate represents one of the most appealing biopolymers for pharmaceutical and biomedical applications. Alginate as a biomaterial for clinical use has been established, although not free from issues. Here we provide a critical review on some of the main recent advances in alginate research in drug delivery and its prominent role in cell microencapsulation for the treatment of diseases, such as type 1 diabetes mellitus. A brief description of the basic properties of the polymer will be provided as well. Based on our experience and contributions, as well as wide research in the field, the correlation between physicochemical and biological properties of alginate systems and clinical outcomes will be investigated and discussed to address the actual future clinical impact of alginatebased delivery strategies.