Chitosan is a linear polysaccharide commercially produced by the deacetylation of chitin. It is non-toxic, biodegradable, biocompatible, and acts as a bioadhesive with otherwise unstable biomolecules ...- making it a valuable component in the formulation of biopharmaceutical drugs. Chitosan-Based Systems for Biopharmaceuticals provides an extensive overview of the application of chitosan and its derivatives in the development and optimisation of biopharmaceuticals. The book is divided in four different parts. Part I discusses general aspects of chitosan and its derivatives, with particular emphasis on issues related to the development of biopharmaceutical chitosan-based systems. Part II deals with the use of chitosan and derivatives in the formulation and delivery of biopharmaceuticals, and focuses on the synergistic effects between chitosan and this particular subset of pharmaceuticals. Part III discusses specific applications of chitosan and its derivatives for biopharmaceutical use. Finally, Part IV presents diverse viewpoints on different issues such as regulatory, manufacturing and toxicological requirements of chitosan and its derivatives related to the development of biopharmaceutical products, as well as their patent status, and clinical application and potential. Topics covered include: * chemical and technological advances in chitins and chitosans useful for the formulation of biopharmaceuticals * physical properties of chitosan and derivatives in sol and gel states * absorption promotion properties of chitosan and derivatives * biocompatibility and biodegradation of chitosan and derivatives * biological and pharmacological activity of chitosan and derivatives * biological, chemical and physical compatibility of chitosan and biopharmaceuticals * approaches for functional modification or crosslinking of chitosan * use of chitosan and derivatives in conventional biopharmaceutical dosage forms * manufacture techniques of chitosan-based microparticles and nanoparticles for biopharmaceuticals * chitosan and derivatives for biopharmaceutical use: mucoadhesive properties * chitosan-based systems for mucosal delivery of biopharmaceuticals * chitosan-based delivery systems for mucosal vaccination * chitosan-based nanoparticulates for oral delivery of biopharmaceuticals * chitosan-based systems for ocular delivery of biopharmaceuticals * chemical modification of chitosan for delivery of DNA and siRNA * target-specific chitosan-based nanoparticle systems for nucleic acid delivery * functional PEGylated chitosan systems for biopharmaceuticals * stimuli-sensitive chitosan-based systems for biopharmaceuticals * chitosan copolymers for biopharmaceuticals * application of chitosan for anti-cancer biopharmaceutical delivery * chitosan-based biopharmaceuticals scaffolds in tissue engineering and regenerative medicine * wound healing properties of chitosan and its use in wound dressing biopharmaceuticals * toxicological properties of chitosan and derivatives for biopharmaceutical applications * regulatory status of chitosan and derivatives * patentability and intellectual property issues * quality control and good manufacturing practice * preclinical and clinical use of chitosan and derivatives for biopharmaceuticals Chitosan-Based Systems for Biopharmaceuticals is an important compendium of fundamental concepts, practical tools and applications of chitosan-based biopharmaceuticals for researchers in academia and industry working in drug formulation and delivery, biopharmaceuticals, medicinal chemistry, pharmacy, bioengineering and new materials development.
The presence of a mucus layer that covers the surface of a variety of organs has been capitalized to develop mucoadhesive dosage forms that remain in the administration site for prolonged times, ...increasing the local and/or systemic bioavailability of the administered drug. The emergence of micro and nanotechnologies together with the implementation of non-invasive and painless administration routes has revolutionized the pharmaceutical market and the treatment of disease. Aiming to overcome the main drawbacks of the oral route and to maintain patient compliance high, the engineering of innovative drug delivery systems administrable by mucosal routes has come to light and gained the interest of the scientific community due to the possibility to dramatically change pharmacokinetics. In addition, to achieve the goal of mucosal drug administration, the development of biomaterials has been refined to fit specific applications. The present review initially describes the potential of nano-drug delivery systems conceived for mucosal administration by diverse non-parenteral routes (e.g., oral, inhalatory, etc.). Then, the benefit of the incorporation of mucoadhesive polymers into the structure of these innovative pharmaceutical products to prolong their residence time in the administration site and the release of the drug cargo will be discussed with focus in the developments of the last decade. In addition, the regulatory status of the most extensively used mucoadhesive polymers will be emphasized. Finally, a thorough overview of the different pharmaceutical applications of mucoadhesive polymers will be addressed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The increasing interest in developing tools to predict drug absorption through mucosal surfaces is fostering the establishment of epithelial cell-based models. Cell-based in vitro techniques for drug ...permeability assessment are less laborious, cheaper and address the concerns of using laboratory animals. Simultaneously, in vitro barrier models that thoroughly simulate human epithelia or mucosae may provide useful data to speed up the entrance of new drugs and new drug products into the clinics. Nevertheless, standard cell-based in vitro models that intend to reproduce epithelial surfaces often discard the role of mucus in influencing drug permeation/absorption. Biomimetic models of mucosae in which mucus production has been considered may not be able to fully reproduce the amount and architecture of mucus, resulting in biased characterization of permeability/absorption. In these cases, artificial mucus may be used to supplement cell-based models but still proper identification and quantification are required. In this review, considerations regarding the relevance of mucus in the development of cell-based epithelial and mucosal models mimicking the gastro-intestinal tract, the cervico-vaginal tract and the respiratory tract, and the impact of mucus on the permeability mechanisms are addressed. From simple epithelial monolayers to more complex 3D structures, the impact of the presence of mucus for the extrapolation to the in vivo scenario is critically analyzed. Finally, an overview is provided on several techniques and methods to characterize the mucus layer over cell-based barriers, in order to intimately reproduce human mucosal layer and thereby, improve in vitro/in vivo correlation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Amorphous products and particularly amorphous solid dispersions are currently one of the most exciting areas in the pharmaceutical field. This approach presents huge potential and advantageous ...features concerning the overall improvement of drug bioavailability.
Currently, different manufacturing processes are being developed to produce amorphous solid dispersions with suitable robustness and reproducibility, ranging from solvent evaporation to melting processes. In the present paper, laboratorial and industrial scale processes were reviewed, and guidelines for a rationale selection of manufacturing processes were proposed. This would ensure an adequate development (laboratorial scale) and production according to the good manufacturing practices (GMP) (industrial scale) of amorphous solid dispersions, with further implications on the process validations and drug development pipeline.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
As the twenty-first century unfolds, nanotechnology is no longer just a buzzword in the field of materials science, but rather a tangible reality. This is evident from the surging number of ...commercial nanoproducts and their corresponding revenue generated in different industry sectors. However, it is important to recognize that sustainable growth of nanotechnology is heavily dependent on government funding and relevant national incentive programs. Consequently, proper analyses on publicly available nanotechnology data sets comprising information on the past two decades can be illuminating, facilitate development, and amend previous strategies as we move forward. Along these lines, classical statistics and machine learning (ML) allow processing large data sets to scrutinize patterns in materials science and nanotechnology research. Herein, we provide an analysis on nanotechnology progress and investment from an unbiased, computational vantage point and using orthogonal approaches. Our data reveal both well-established and surprising correlations in the nanotechnology field and its actors, including the interplay between the number of research institutes–industry, publications–patents, collaborative research, and top contributors to nanoproducts. Overall, data suggest that, supported by incentive programs set out by stakeholders (researchers, funding agencies, policy makers, and industry), nanotechnology could experience an exponential growth and become a centerpiece for economical welfare. Indeed, the recent success of COVID-19 vaccines is also likely to boost public trust in nanotechnology and its global impact over the coming years.
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IJS, KILJ, NUK, PNG, UL, UM
Mucosal tissues constitute the largest interface between the body and the surrounding environment and they regulate the access of molecules, supramolecular structures, particulate matter, and ...pathogens into it. All mucosae are characterized by an outer mucus layer that protects the underlying cells from physicochemical, biological and mechanical insults, a mono-layered or stratified epithelium that forms tight junctions and controls the selective transport of solutes across it and associated lymphoid tissues that play a sentinel role. Mucus is a gel-like material comprised mainly of the glycoprotein mucin and water and it displays both hydrophilic and hydrophobic domains, a net negative charge, and high porosity and pore interconnectivity, providing an efficient barrier for the absorption of therapeutic agents. To prolong the residence time, absorption and bioavailability of a broad spectrum of active compounds upon mucosal administration, mucus-penetrating and mucoadhesive particles have been designed by tuning the chemical composition, the size, the density, and the surface properties. The benefits of utilizing nanomaterials that interact intimately with mucosae by different mechanisms in the nanomedicine field have been extensively reported. To ensure the safety of these nanosystems, their compatibility is evaluated
in vitro
and
in vivo
in preclinical and clinical trials. Conversely, there is a growing concern about the toxicity of nanomaterials dispersed in air and water effluents that unintentionally come into contact with the airways and the gastrointestinal tract. Thus, deep understanding of the key nanomaterial properties that govern the interplay with mucus and tissues is crucial for the rational design of more efficient drug delivery nanosystems (nanomedicine) and to anticipate the fate and side-effects of nanoparticulate matter upon acute or chronic exposure (nanotoxicology). This review initially overviews the complex structural features of mucosal tissues, including the structure of mucus, the epithelial barrier, the mucosal-associated lymphatic tissues and microbiota. Then, the most relevant investigations attempting to identify and validate the key particle features that govern nanomaterial-mucosa interactions and that are relevant in both nanomedicine and nanotoxicology are discussed in a holistic manner. Finally, the most popular experimental techniques and the incipient use of mathematical and computational models to characterize these interactions are described.
This review provides an integrative overview of the complex interactions between nanomaterials and mucosae, and their implications to nanomedicine and nanotoxicology.
Electrospun fibrous membranes provide suitable physical anti-adhesion barriers for reducing tissue anti-adhesion following surgery. However, often during the biodegradation process, these barriers ...trigger inflammation and cause a foreign body reaction with subsequent decrease in anti-adhesion efficacy. Here, a facile strategy comprising the incorporation of ibuprofen (IBU) into implantable membranes and its sustained release was proposed in order to improve anti-adhesion effects and neurological outcomes, namely to prevent failed back surgery syndrome (FBSS). The combination of free IBU and a newly synthetized polymeric prodrug of IBU, namely poly(hydroxyethyl methacrylate) with ester-linked IBU, was successfully used in order to reduce initial burst drug release and provide sustained drug release from fibrous membranes throughout several weeks. Such release profile was shown useful in preventing both acute and chronic inflammation in rats following laminectomy and membrane implantation. Moreover, histological analysis provided evidence of an excellent anti-adhesion effect, while associated neurological deficits were effectively reduced. Furthermore, the assessment of macrophage density, neovascularization, and related gene expression at the lesion site revealed that a sustained anti-inflammatory effect was achieved with the IBU-loaded proposed fibrous membranes. Results suggested that the COX2 pathway plays an important role in the development epidural fibrosis and arachnoiditis. Overall, this study provided evidence that precisely engineered IBU-loaded electrospun fibrous membranes may be useful in preventing FBSS and able to potentially impact the outcome of patients undergoing spine surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The vaginal delivery of various drugs is well described and its relevance established in current medical practice. Alongside recent advances and achievements in the fields of pharmaceutical ...nanotechnology and nanomedicine, there is an increasing interest in the potential use of different nanocarriers for the delivery of old and new pharmacologically active molecules with either therapeutic or prophylactic purposes. Nanosystems of polymeric nature in particular have been investigated over the last years and their interactions with mucosal fluids and tissues, as well as genital tract biodistribution upon vaginal administration, are now better understood. While different applications have been envisioned, most of the current research is focusing in the development of nano-formulations with the potential to inhibit the vaginal transmission of HIV upon sexual intercourse. The present work focuses its discussion on the potential and perils of polymer-based nanocarriers for the vaginal administration of different pharmacologically active molecules.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 ...decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood-brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS.
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Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. ...Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box–Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box–Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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