In recent decades, collagen is one of the most versatile biomaterials used in biomedical applications, mostly due to its biomimetic and structural composition in the extracellular matrix (ECM). ...Several attempts are proposed for designing innovative collagen‐based biomaterials and applying them in tissue regeneration. The regeneration of different tissues is prompted by different types and diverse physical forms of collagen‐based biomaterials prepared by various methods. Based on such concepts, the source, structure, and classification of collagen are briefly introduced in this review. Here, the commonly used physical forms and modification methods of collagen‐based biomaterials are reviewed, including hydrogels, scaffolds, and microspheres, followed by their applications in the regeneration of tissues and organs. Important proof‐of‐concept examples are described to demonstrate the outcomes on material characteristics, cellular reactions, and tissue regeneration. A concise assessment of the limitations that still exist and the developing trends in the future of collagen‐based biomaterials are put forward.
In this review, an overview of the different physical forms of collagen‐based biomaterials is provided and the corresponding commonly used fabrication methods as well as advanced technologies in detail followed by examples of their applications in the regeneration of tissues and organs are discussed. The limitations and potential development directions are also listed at the end.
Lyophilization has been used to improve the long-term stability of polymeric nanoparticles for drug delivery applications, avoiding their instability in suspension. However, this dehydration process ...may induce stresses to nanoparticles, mitigated by the use of some excipients such as cryo- and lyoprotectants. Still, the lyophilization of polymeric nanoparticles is frequently based in empirical principles, without considering the physical–chemical properties of formulations and the engineering principles of lyophilization. Therefore, the optimization of formulations and the lyophilization cycle is crucial to obtain a good lyophilizate, and guarantee the preservation of nanoparticle stability. The proper characterization of the lyophilizate and nanoparticles has a great importance in achieving these purposes. This review updates the fundaments involved in the optimization procedures for lyophilization of polymeric nanoparticles, with the aim of obtaining the maximum stability of formulations. Different characterization methods to obtain and guarantee a good lyophilized product are also discussed. A special focus is given to encapsulated therapeutic proteins. Overall, this review is a contribution for the understanding of the parameters involved in the lyophilization of polymeric nanoparticles. This may definitely help future works to obtain lyophilized nanoparticles with good quality and with improved therapeutic benefits.
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Solid dispersions are one of the most promising strategies to improve the oral bioavailability of poorly water soluble drugs. By reducing drug particle size to the absolute minimum, and hence ...improving drug wettability, bioavailability may be significantly improved. They are usually presented as amorphous products, mainly obtained by two major different methods, for example, melting and solvent evaporation. Recently, surfactants have been included to stabilize the formulations, thus avoiding drug recrystallization and potentiating their solubility. New manufacturing processes to obtain solid dispersions have also been developed to reduce the drawbacks of the initial process. In this review, it is intended to discuss the recent advances related on the area of solid dispersions.
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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Cellular transport study of RVG-9R-BACE1 siRNA complex included into uncoated (NR) and chitosan coated (C) solid lipid nanoparticles (SLN) using Caco-2 as a model of epithelial-like phenotypes.
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•SLNs were proposed for an efficient and optimal nose-to-brain transport of BACE1 siRNA.•Coated and un-coated SLNs as nasal delivery system of BACE1 siRNA were designed.•RVG-9R/BACE1 siRNA complex was chosen for increasing transcellular nerve pathway.•Total encapsulation of RVG-9R/BACE1 siRNA was obtained with chitosan coating.•Chitosan coated and uncoated SLNs increase siRNA permeation through epithelial cells.
We designed a delivery system to obtain an efficient and optimal nose-to-brain transport of BACE1 siRNA, potentially useful in the treatment of Alzheimer's disease. We selected a cell-penetrating peptide, the short peptide derived from rabies virus glycoprotein known as RVG-9R, to increase the transcellular pathway in neuronal cells. The optimal molar ratio between RVG-9R and BACE1 siRNA was elucidated. The complex between the two was then encapsulated. We propose chitosan-coated and uncoated solid lipid nanoparticles (SLNs) as a nasal delivery system capable of exploiting both olfactory and trigeminal nerve pathways. The coating process had an effect on the zeta potential, obtaining positively-charged nanoparticles, and on siRNA protection. The positive charge of the coating formulation ensured mucoadhesiveness to the particles and also prolonged residence time in the nasal cavity. We studied the cellular transport of siRNA released from the SLNs using Caco-2 as a model of epithelial-like phenotypes. We found that siRNA permeates the monolayer to a greater extent when released from any of the studied formulations than from bare siRNA, and primarily from chitosan-coated SLNs.
Monoclonal antibodies have deserved a remarkable interest for more than 40 years as a vital tool for the treatment of various diseases. Still, there is a raising interest to develop advanced ...monoclonal antibody delivery systems able to tailor pharmacokinetics. Bevacizumab is a humanized immunoglobulin IgG1 used in antiangiogenic therapies due to its capacity to inhibit the interaction between vascular endothelial growth factor and its receptor. However, bevacizumab-based antiangiogenic therapy is not always effective due to poor treatment compliance associated to multiples administrations and drug resistance. In this work, we show a promising strategy of encapsulating bevacizumab to protect and deliver it, in a controlled manner, increasing the time between administrations and formulation shelf-life. Nanoencapsulation of bevacizumab represents a significant advance for selective antiangiogenic therapies since extracellular, cell surface and intracellular targets can be reached. The present study shows that bevacizumab-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles does not impair its native-like structure after encapsulation and fully retain the bioactivity, making this nanosystem a new paradigm for the improvement of angiogenic therapy.
The stratum corneum (SC) is the skin's outermost layer, organized by clusters of corneocytes among a lipid matrix, acting as a barrier. This “brick and mortar” organization is modified in many skin ...diseases. We proposed a lesioned-skin model for assessing the permeability of topical formulations and the impact of skin integrity on the permeability of molecules. We anticipate that removal of the SC compromises the skin barrier function, making it more permeable, affecting the biopharmaceutics of topical formulations. By stripping with 25 strips (Corneofix®), the thickness of the SC was considerably reduced, exposing the viable epidermis. Transversal and upper views of the skin by electronic microscopy and histology confirm the removal of the SC. After, we evaluated the permeability of tacrolimus (Protopic®, 0.1 % and 0.03 %) by HPLC-UV. The non-lesioned skin presented 20–25 % of tacrolimus in the SC and no drug permeated through the skin’s inner layers. Contrary, the lesioned-skin model allowed the permeation of tacrolimus to the epidermis, dermis, and also in the receptor medium. These results highlight the importance of using diseased skin tissue as opposed to normal skin when assessing the permeability of pharmaceutical formulations for local topical delivery, closely mimicking the occurred events in clinical scenario.
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•Lesioned-model by decreasing the stratum corneum thickness and its disruption.•Ex vivo modeling the effect of stratum corneum thickness over drugs’ permeability.•Tacrolimus exhibited an increase of 20 % of permeability in lesioned-model.
Despite its complexity, the human body is composed of only four basic tissue types, namely epithelial, connective, muscular and nervous tissues. Notably, each tissue is an assemblage of similarly ...functional cells united in performing a specific function. Instead of mimicking functionality mechanically, three-dimensional (3D) bioprinting based on histological categories is a strategy designed with multiple materials and techniques, which is a versatile technology able to form functional organ structures in line with simplicity. This review aims to provide an overview of tissue-specific 3D bioprinting based on the biological characteristics of four tissue types, including the histological features, biomaterials and corresponding applications. It first briefly introduces the goals of tissue-specific bioprinting and then summarizes the major techniques and identification of particular material development. Moreover, its remarkable regenerative power in replacement therapy and novel outbreak in particular tissues are assembled by epithelial, connective, nerve and muscle tissues. Finally, we discuss challenges and future prospects of tissue-specific based 3D bioprinting in biomedicine, hoping to further inspire the development.
Despite its complexity, the human body are composed of only four basic tissue types: epithelial, connective, muscular, and nervous tissues and each is an assemblage of similarly functional cells united in performing a specific function. Instead of mimicking functionality mechanically, the three-dimensional bioprinting (3D bioprinting) based on histological categories is a strategy designed with multiple materials and techniques, which is a versatile technology able to form functional organ structures in line with simplicity. Display omitted
Hypericum perforatum is a perennial plant, with worldwide distribution, commonly known as St. John's wort. It has been used for centuries in traditional medicine for the treatment of several ...disorders, such as minor burns, anxiety, and mild to moderate depression. In the past years, its antidepressant properties have been extensively studied. Despite that, other H. perforatum biological activities, as its neuroprotective properties have also been evaluated. The present review aims to provide a comprehensive summary of the main biologically active compounds of H. perforatum, as for its chemistry, pharmacological activities, drug interactions and adverse reactions and gather scattered information about its neuroprotective abilities. As for this, it has been demonstrated that H. perforatum extracts and several of its major molecular components have the ability to protect against toxic insults, either directly, through neuroprotective mechanisms, or indirectly, through is antioxidant properties. H. perforatum has therefore the potential to become an effective neuroprotective therapeutic agent, despite further studies that need to be carried out.
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Stent implantation is a well-accepted alternative to treat benign luminal disease (BLD). Current stents are often fabricated from plastic, mental and biodegradable materials, and the ...latter two have wider clinical application. Self-expanding plastic and mental stents possessed many disadvantages such as stent migration, tissue hyperplasia, in-stent restenosis and are difficult to remove, which catalyzes the development of biodegradable stent (BDS). In fact, BDS are not required to be removed upon implementation and leaves no residues in tissue after complete biodegradation compared to metallic or plastic stents. In vascular system, BDS, also termed bioresorbable vascular scaffold (BVS) have also been used to treat luminal stenotic or occlusive lesions in cardiovascular system, peripheral arteries system and veins. In nonvascular system, BDS, with either bare or covered designs, was employed for the treatment of occlusion, stenosis, anastomosis, leak, fistula or perforation of digestive (esophagus, gastrointestinal, biliary, pancreatobiliary, hepatobiliary), respiratory (airway), and urinary (ureteral, urethral). However, the weak radial force, in-stent thrombosis and restenosis become main issues of BDS or BVS and restrict its further clinical application. Therefore, more intensive researches are expected on the strengthening of the radial force of BDS and development of novel drug eluting techniques on its surface to prevent thrombus or restenosis. In this review it is given an updated outline of the use of BDS to treat BLD in a minimal invasive way and explore its advantages and disadvantages for a vast range of fields ranging from cardiovascular to digestive and urinary system. Further discussion to foster the investigation and development of this approach in clinical is also provided.
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