Showing papers in "Pharmaceutics in 2021"

Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions

Abstract: Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that has gained great attention in the past years as a new therapy for cancer treatment. PDT uses photosensitizers that, after being excited by light at a specific wavelength, react with the molecular oxygen to create reactive oxygen species in the target tissue, resulting in cell death. Compared to conventional therapeutic modalities, PDT presents greater selectivity against tumor cells, due to the use of photosensitizers that are preferably localized in tumor lesions, and the precise light irradiation of these lesions. This paper presents a review of the principles, mechanisms, photosensitizers, and current applications of PDT. Moreover, the future path on the research of new photosensitizers with enhanced tumor selectivity, featuring the improvement of PDT effectiveness, has also been addressed. Finally, new applications of PDT have been covered.

Detection of Microplastic in Human Placenta and Meconium in a Clinical Setting.

Abstract: Environmental pollution with microplastics (MPs) is a major and worldwide concern. Involuntary exposure to MPs by ingestion or inhalation is unavoidable. The effects on human health are still under debate, while in animals, cellular MP translocation and subsequent deleterious effects were shown. First reports indicate a potential intrauterine exposure with MPs, yet readouts are prone to contamination. Method: To establish a thorough protocol for the detection of MPs in human placenta and fetal meconium in a real-life clinical setting, a pilot study was set up to screen for MPs > 50 µm in placental tissue and meconium sampled during two cesarean sections for breech deliveries. After chemical digestion of non-plastic material, Fourier-transform infrared (FTIR) microspectroscopy was used to analyze the presence of 10 common types of microplastic in placenta and stool samples. Results: Human placenta and meconium samples were screened positive for polyethylene, polypropylene, polystyrene, and polyurethane, of which only the latter one was also detected as airborne fallout in the operating room—thus representing potential contamination. Conclusion: We found MPs > 50 µm in placenta and meconium acquired from cesarean delivery. Critical evaluation of potential contamination sources is pivotal and may guide future clinical studies to improve the correct detection of MPs in organ tissue. Studies investigating nano-sized plastics in human tissue are warranted.

Lipid nanoparticles as delivery systems for RNA-based vaccines

Abstract: There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer.

Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management.

Abstract: The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels such as DNA hydrogels are extensively discussed in this review. Different types of cross-linking techniques, materials utilized, procedures, advantages, and disadvantages covering hydrogels are tabulated. The application of hydrogels, particularly in buccal, oral, vaginal, and transdermal drug delivery systems, are described. The review also focuses on composite hydrogels with enhanced properties that are being developed to meet the diverse demand of wound dressing materials. The unique advantages of hydrogel nanoparticles in targeted and intracellular delivery of various therapeutic agents are explained. Furthermore, different types of hydrogel-based materials utilized for tissue engineering applications and fabrication of contact lens are discussed. The article also provides an overview of selected examples of commercial products launched particularly in the area of oral and ocular drug delivery systems and wound dressing materials. Hydrogels can be prepared with a wide variety of properties, achieving biostable, bioresorbable, and biodegradable polymer matrices, whose mechanical properties and degree of swelling are tailored with a specific application. These unique features give them a promising future in the fields of drug delivery systems and applied biomedicine.

Unlocking the Power of Exosomes for Crossing Biological Barriers in Drug Delivery.

Abstract: Since the 2013 Nobel Prize was awarded for the discovery of vesicle trafficking, a subgroup of nanovesicles called exosomes has been driving the research field to a new regime for understanding cellular communication. This exosome-dominated traffic control system has increased understanding of many diseases, including cancer metastasis, diabetes, and HIV. In addition to the important diagnostic role, exosomes are particularly attractive for drug delivery, due to their distinctive properties in cellular information transfer and uptake. Compared to viral and non-viral synthetic systems, the natural, cell-derived exosomes exhibit intrinsic payload and bioavailability. Most importantly, exosomes easily cross biological barriers, obstacles that continue to challenge other drug delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), blood-lymph barrier (BlyB), blood-air barrier (BAB), stromal barrier (SB), blood-labyrinth barrier (BLaB), blood-retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform. However, the systematic reviews summarizing such discoveries are still limited. This review covers state-of-the-art exosome research on crossing several important biological barriers with a focus on the current, accepted models used to explain the mechanisms of barrier crossing, including tight junctions. The potential to design and engineer exosomes to enhance delivery efficacy, leading to future applications in precision medicine and immunotherapy, is discussed.

TLR Agonists as Vaccine Adjuvants Targeting Cancer and Infectious Diseases.

Abstract: Modern vaccines have largely shifted from using whole, killed or attenuated pathogens to being based on subunit components. Since this diminishes immunogenicity, vaccine adjuvants that enhance the immune response to purified antigens are critically needed. Further advantages of adjuvants include dose sparing, increased vaccine efficacy in immunocompromised individuals and the potential to protect against highly variable pathogens by broadening the immune response. Due to their ability to link the innate with the adaptive immune response, Toll-like receptor (TLR) agonists are highly promising as adjuvants in vaccines against life-threatening and complex diseases such as cancer, AIDS and malaria. TLRs are transmembrane receptors, which are predominantly expressed by innate immune cells. They can be classified into cell surface (TLR1, TLR2, TLR4, TLR5, TLR6) and intracellular TLRs (TLR3, TLR7, TLR8, TLR9), expressed on endosomal membranes. Besides a transmembrane domain, each TLR possesses a leucine-rich repeat (LRR) segment that mediates PAMP/DAMP recognition and a TIR domain that delivers the downstream signal transduction and initiates an inflammatory response. Thus, TLRs are excellent targets for adjuvants to provide a "danger" signal to induce an effective immune response that leads to long-lasting protection. The present review will elaborate on applications of TLR ligands as vaccine adjuvants and immunotherapeutic agents, with a focus on clinically relevant adjuvants.

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives.

Abstract: Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.

Scale-up of Electrospinning: Market Overview of Products and Devices for Pharmaceutical and Biomedical Purposes.

Abstract: Recently, the electrospinning (ES) process has been extensively studied due to its potential applications in various fields, particularly pharmaceutical and biomedical purposes. The production rate using typical ES technology is usually around 0.01–1 g/h, which is lower than pharmaceutical industry production requirements. Therefore, different companies have worked to develop electrospinning equipment, technological solutions, and electrospun materials into large-scale production. Different approaches have been explored to scale-up the production mainly by increasing the nanofiber jet through multiple needles, free-surface technologies, and hybrid methods that use an additional energy source. Among them, needleless and centrifugal methods have gained the most attention and applications. Besides, the production rate reached (450 g/h in some cases) makes these methods feasible in the pharmaceutical industry. The present study overviews and compares the most recent ES approaches successfully developed for nanofibers’ large-scale production and accompanying challenges with some examples of applied approaches in drug delivery systems. Besides, various types of commercial products and devices released to the markets have been mentioned.

Multi-Component Hydrogel Beads Incorporated with Reduced Graphene Oxide for pH-Responsive and Controlled Co-Delivery of Multiple Agents.

Abstract: The development of combination therapy has received great attention in recent years because of its potential to achieve higher therapeutic efficacy than that achieved by mono-drug therapy. Carriers for effective and stimuli-responsive co-delivery of multiple agents, however, are highly deficient at the moment. To address this need, this study reports the generation of multi-component hydrogel beads incorporated with reduced graphene oxide (rGO). The beads are prepared by incorporating doxorubicin (DOX)-loaded gelatine (GL) microbeads into hydrogel beads containing rGO and 5-fluorouracil (5-FU). rGO-containing beads are shown to be more effective in inhibiting the growth of MCF-7 cells via the induction of reactive oxygen species (ROS) generation. In addition, the drug release sustainability of the beads is affected by the pH of the release medium, with the release rate increasing in neutral pH but decreasing in the acidic environment. Our beads warrant further development as carriers for pH-responsive and controlled co-delivery of multiple agents.

Magnetic Nanoparticles in Biology and Medicine: Past, Present, and Future Trends.

Abstract: The use of magnetism in medicine has changed dramatically since its first application by the ancient Greeks in 624 BC. Now, by leveraging magnetic nanoparticles, investigators have developed a range of modern applications that use external magnetic fields to manipulate biological systems. Drug delivery systems that incorporate these particles can target therapeutics to specific tissues without the need for biological or chemical cues. Once precisely located within an organism, magnetic nanoparticles can be heated by oscillating magnetic fields, which results in localized inductive heating that can be used for thermal ablation or more subtle cellular manipulation. Biological imaging can also be improved using magnetic nanoparticles as contrast agents; several types of iron oxide nanoparticles are US Food and Drug Administration (FDA)-approved for use in magnetic resonance imaging (MRI) as contrast agents that can improve image resolution and information content. New imaging modalities, such as magnetic particle imaging (MPI), directly detect magnetic nanoparticles within organisms, allowing for background-free imaging of magnetic particle transport and collection. “Lab-on-a-chip” technology benefits from the increased control that magnetic nanoparticles provide over separation, leading to improved cellular separation. Magnetic separation is also becoming important in next-generation immunoassays, in which particles are used to both increase sensitivity and enable multiple analyte detection. More recently, the ability to manipulate material motion with external fields has been applied in magnetically actuated soft robotics that are designed for biomedical interventions. In this review article, the origins of these various areas are introduced, followed by a discussion of current clinical applications, as well as emerging trends in the study and application of these materials.

Naringenin Nano-Delivery Systems and Their Therapeutic Applications

Abstract: Naringenin (NRG) is a polyphenolic phytochemical belonging to the class of flavanones and is widely distributed in citrus fruits and some other fruits such as bergamot, tomatoes, cocoa, and cherries. NRG presents several interesting pharmacological properties, such as anti-cancer, anti-oxidant, and anti-inflammatory activities. However, the therapeutic potential of NRG is hampered due to its hydrophobic nature, which leads to poor bioavailability. Here, we review a wide range of nanocarriers that have been used as delivery systems for NRG, including polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanosuspensions, and nanoemulsions. These nanomedicine formulations of NRG have been applied as a potential treatment for several diseases, using a wide range of in vitro, ex vivo, and in vivo models and different routes of administration. From this review, it can be concluded that NRG is a potential therapeutic option for the treatment of various diseases such as cancer, neurological disorders, liver diseases, ocular disorders, inflammatory diseases, skin diseases, and diabetes when formulated in the appropriate nanocarriers.

Essential Oils: Pharmaceutical Applications and Encapsulation Strategies into Lipid-Based Delivery Systems.

Abstract: Essential oils are being studied for more than 60 years, but a growing interest has emerged in the recent decades due to a desire for a rediscovery of natural remedies. Essential oils are known for millennia and, already in prehistoric times, they were used for medicinal and ritual purposes due to their therapeutic properties. Using a variety of methods refined over the centuries, essential oils are extracted from plant raw materials: the choice of the extraction method is decisive, since it determines the type, quantity, and stereochemical structure of the essential oil molecules. To these components belong all properties that make essential oils so interesting for pharmaceutical uses; the most investigated ones are antioxidant, anti-inflammatory, antimicrobial, wound-healing, and anxiolytic activities. However, the main limitations to their use are their hydrophobicity, instability, high volatility, and risk of toxicity. A successful strategy to overcome these limitations is the encapsulation within delivery systems, which enable the increase of essential oils bioavailability and improve their chemical stability, while reducing their volatility and toxicity. Among all the suitable platforms, our review focused on the lipid-based ones, in particular micro- and nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers.

Biodegradable Alginate Films with ZnO Nanoparticles and Citronella Essential Oil-A Novel Antimicrobial Structure.

Abstract: The petroleum-based materials could be replaced, at least partially, by biodegradable packaging. Adding antimicrobial activity to the new packaging materials can also help improve the shelf life of food and diminish the spoilage. The objective of this research was to obtain a novel antibacterial packaging, based on alginate as biodegradable polymer. The antibacterial activity was induced to the alginate films by adding various amounts of ZnO nanoparticles loaded with citronella (lemongrass) essential oil (CEO). The obtained films were characterized, and antibacterial activity was tested against two Gram-negative (Escherichia coli and Salmonella Typhi) and two Gram-positive (Bacillus cereus and Staphylococcus aureus) bacterial strains. The results suggest the existence of synergy between antibacterial activities of ZnO and CEO against all tested bacterial strains. The obtained films have a good antibacterial coverage, being efficient against several pathogens, the best results being obtained against Bacillus cereus. In addition, the films presented better UV light barrier properties and lower water vapor permeability (WVP) when compared with a simple alginate film. The preliminary tests indicate that the alginate films with ZnO nanoparticles and CEO can be used to successfully preserve the cheese. Therefore, our research evidences the feasibility of using alginate/ZnO/CEO films as antibacterial packaging for cheese in order to extend its shelf life.

Improving Curcumin Bioavailability: Current Strategies and Future Perspectives

Abstract: Curcumin possesses a plethora of interesting pharmacological effects. Unfortunately, it is also characterized by problematic drug delivery and scarce bioavailability, representing the main problem related to the use of this compound. Poor absorption, fast metabolism, and rapid systemic clearance are the most important factors contributing to low curcumin levels in plasma and tissues. Accordingly, to overcome these issues, numerous strategies have been proposed and are investigated in this article. Due to advances in the drug delivery field, we describe here the most promising strategies for increasing curcumin bioavailability, including the use of adjuvant, complexed/encapsulated curcumin, specific curcumin formulations, and curcumin nanoparticles. We analyze current strategies, already available in the market, and the most advanced technologies that can offer a future perspective for effective curcumin formulations. We focus the attention on the effectiveness of curcumin-based formulations in clinical trials, providing a comprehensive summary. Clinical trial results, employing various delivery methods for curcumin, showed that improved bioavailability corresponds to increased therapeutic efficacy. Furthermore, advances in the field of nanoparticles hold great promise for developing curcumin-based complexes as effective therapeutic agents. Summarizing, suitable delivery methods for this polyphenol will ensure the possibility of using curcumin-derived formulations in clinical practice as preventive and disease-modifying therapeutics.

Solid Lipid Nanoparticles (SLNs): An Advanced Drug Delivery System Targeting Brain through BBB.

Abstract: The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

Potential of Cyanine Derived Dyes in Photodynamic Therapy.

Abstract: Photodynamic therapy (PDT) is a method of cancer treatment that leads to the disintegration of cancer cells and has developed significantly in recent years. The clinically used photosensitizers are primarily porphyrin, which absorbs light in the red spectrum and their absorbance maxima are relatively short. This review presents group of compounds and their derivatives that are considered to be potential photosensitizers in PDT. Cyanine dyes are compounds that typically absorb light in the visible to near-infrared-I (NIR-I) spectrum range (750-900 nm). This meta-analysis comprises the current studies on cyanine dye derivatives, such as indocyanine green (so far used solely as a diagnostic agent), heptamethine and pentamethine dyes, squaraine dyes, merocyanines and phthalocyanines. The wide array of the cyanine derivatives arises from their structural modifications (e.g., halogenation, incorporation of metal atoms or organic structures, or synthesis of lactosomes, emulsions or conjugation). All the following modifications aim to increase solubility in aqueous media, enhance phototoxicity, and decrease photobleaching. In addition, the changes introduce new features like pH-sensitivity. The cyanine dyes involved in photodynamic reactions could be incorporated into sets of PDT agents.

Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery.

Abstract: The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

Co-Amorphous Drug Formulations in Numbers: Recent Advances in Co-Amorphous Drug Formulations with Focus on Co-Formability, Molar Ratio, Preparation Methods, Physical Stability, In Vitro and In Vivo Performance, and New Formulation Strategies

Abstract: Co-amorphous drug delivery systems (CAMS) are characterized by the combination of two or more (initially crystalline) low molecular weight components that form a homogeneous single-phase amorphous system. Over the past decades, CAMS have been widely investigated as a promising approach to address the challenge of low water solubility of many active pharmaceutical ingredients. Most of the studies on CAMS were performed on a case-by-case basis, and only a few systematic studies are available. A quantitative analysis of the literature on CAMS under certain aspects highlights not only which aspects have been of great interest, but also which future developments are necessary to expand this research field. This review provides a comprehensive updated overview on the current published work on CAMS using a quantitative approach, focusing on three critical quality attributes of CAMS, i.e., co-formability, physical stability, and dissolution performance. Specifically, co-formability, molar ratio of drug and co-former, preparation methods, physical stability, and in vitro and in vivo performance were covered. For each aspect, a quantitative assessment on the current status was performed, allowing both recent advances and remaining research gaps to be identified. Furthermore, novel research aspects such as the design of ternary CAMS are discussed.

Inorganic Nanoparticles Applied for Active Targeted Photodynamic Therapy of Breast Cancer.

Abstract: Photodynamic therapy (PDT) is an alternative modality to conventional cancer treatment, whereby a specific wavelength of light is applied to a targeted tumor, which has either a photosensitizer or photochemotherapeutic agent localized within it. This light activates the photosensitizer in the presence of molecular oxygen to produce phototoxic species, which in turn obliterate cancer cells. The incidence rate of breast cancer (BC) is regularly growing among women, which are currently being treated with methods, such as chemotherapy, radiotherapy, and surgery. These conventional treatment methods are invasive and often produce unwanted side effects, whereas PDT is more specific and localized method of cancer treatment. The utilization of nanoparticles in PDT has shown great advantages compared to free photosensitizers in terms of solubility, early degradation, and biodistribution, as well as far more effective intercellular penetration and uptake in targeted cancer cells. This review gives an overview of the use of inorganic nanoparticles (NPs), including: gold, magnetic, carbon-based, ceramic, and up-conversion NPs, as well as quantum dots in PDT over the last 10 years (2009 to 2019), with a particular focus on the active targeting strategies for the PDT treatment of BC.

Electrically Triggered Drug Delivery from Novel Electrospun Poly(Lactic Acid)/Graphene Oxide/Quercetin Fibrous Scaffolds for Wound Dressing Applications

Abstract: The novel controlled and localized delivery of drug molecules to target tissues using an external electric stimulus makes electro-responsive drug delivery systems both feasible and desirable, as well as entailing a reduction in the side effects. Novel micro-scaffold matrices were designed based on poly(lactic acid) (PLA) and graphene oxide (GO) via electrospinning. Quercetin (Q), a natural flavonoid, was loaded into the fiber matrices in order to investigate the potential as a model drug for wound dressing applications. The physico-chemical properties, electrical triggering capacity, antimicrobial assay and biocompatibility were also investigated. The newly fabricated PLA/GO/Q scaffolds showed uniform and smooth surface morphologies, without any beads, and with diameters ranging from 1107 nm (10%PLA/0.1GO/Q) to 1243 nm (10%PLA). The in vitro release tests of Q from the scaffolds showed that Q can be released much faster (up to 8640 times) when an appropriate electric field is applied compared to traditional drug-release approaches. For instance, 10 s of electric stimulation is enough to ensure the full delivery of the loaded Q from the 10%PLA/1%GO/Q microfiber scaffold at both 10 Hz and at 50 Hz. The antimicrobial tests showed the inhibition of bacterial film growth. Certainly, these materials could be loaded with more potent agents for anti-cancer, anti-infection, and anti-osteoporotic therapies. The L929 fibroblast cells cultured on these scaffolds were distributed homogeneously on the scaffolds, and the highest viability value of 82.3% was obtained for the 10%PLA/0.5%GO/Q microfiber scaffold. Moreover, the addition of Q in the PLA/GO matrix stimulated the production of IL-6 at 24 h, which could be linked to an acute inflammatory response in the exposed fibroblast cells, as a potential effect of wound healing. As a general conclusion, these results demonstrate the possibility of developing graphene oxide-based supports for the electrically triggered delivery of biological active agents, with the delivery rate being externally controlled in order to ensure personalized release.

Current Update of Collagen Nanomaterials—Fabrication, Characterisation and Its Applications: A Review

Abstract: Tissue engineering technology is a promising alternative approach for improvement in health management. Biomaterials play a major role, acting as a provisional bioscaffold for tissue repair and regeneration. Collagen a widely studied natural component largely present in the extracellular matrix (ECM) of the human body. It provides mechanical stability with suitable elasticity and strength to various tissues, including skin, bone, tendon, cornea and others. Even though exogenous collagen is commonly used in bioscaffolds, largely in the medical and pharmaceutical fields, nano collagen is a relatively new material involved in nanotechnology with a plethora of unexplored potential. Nano collagen is a form of collagen reduced to a nanoparticulate size, which has its advantages over the common three-dimensional (3D) collagen design, primarily due to its nano-size contributing to a higher surface area-to-volume ratio, aiding in withstanding large loads with minimal tension. It can be produced through different approaches including the electrospinning technique to produce nano collagen fibres resembling natural ECM. Nano collagen can be applied in various medical fields involving bioscaffold insertion or fillers for wound healing improvement; skin, bone, vascular grafting, nerve tissue and articular cartilage regeneration as well as aiding in drug delivery and incorporation for cosmetic purposes.

pH-Sensitive Alginate/Carboxymethyl Chitosan/Aminated Chitosan Microcapsules for Efficient Encapsulation and Delivery of Diclofenac Sodium.

Abstract: To develop an effective pH-sensitive drug carrier, alginate (Alg), carboxymethyl chitosan (CMCs), and aminated chitosan (AmCs) derivatives were employed in this study. A simple ionic gelation technique was employed to formulate Alg-CMCs@AmCs dual polyelectrolyte complexes (PECs) microcapsules as a pH-sensitive carrier for efficient encapsulation and release of diclofenac sodium (DS) drug. The developed microcapsules were characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analyzer (TGA), and scanning electron microscope (SEM). The results clarified that formation of dual PECs significantly protected Alg microcapsules from rapid disintegration at colon conditions (pH 7.4), and greatly reduced their porosity. In addition, the dual PECs microcapsules can effectively encapsulate 95.4% of DS-drug compared to 86.3 and 68.6% for Alg and Alg-CMCs microcapsules, respectively. Higher DS-release values were achieved in simulated colonic fluid [SCF; pH 7.4] compared to those obtained in simulated gastric fluid [SGF; pH 1.2]. Moreover, the drug burst release was prevented and a sustained DS-release was achieved as the AmCs concentration increased. The results confirmed also that the developed microcapsules were biodegradable in the presence of the lysozyme enzyme. These findings emphasize that the formulated pH-sensitive microcapsules could be applied for the delivery of diclofenac sodium.

Inhalation Delivery for the Treatment and Prevention of COVID-19 Infection

Abstract: Coronavirus disease-2019 (COVID-19) is caused by coronavirus-2 (SARS-CoV-2) and has produced a global pandemic. As of 22 June 2021, 178 million people have been affected worldwide, and 3.87 million people have died from COVID-19. According to the Centers for Disease Control and Prevention (CDC) of the United States, COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes. Since the location of initial infection and disease progression is primarily through the lungs, the inhalation delivery of drugs directly to the lungs may be the most appropriate route of administration for treating COVID-19. This review article aims to present possible inhalation therapeutics and vaccines for the treatment of COVID-19 symptoms. This review covers the comparison between SARS-CoV-2 and other coronaviruses such as SARS-CoV/MERS, inhalation therapeutics for the treatment of COVID-19 symptoms, and vaccines for preventing infection, as well as the current clinical status of inhaled therapeutics and vaccines.

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

Abstract: The efficient and safe delivery of therapeutic drugs, proteins, and nucleic acids are essential for meaningful therapeutic benefits. The field of nanomedicine shows promising implications in the development of therapeutics by delivering diagnostic and therapeutic compounds. Nanomedicine development has led to significant advances in the design and engineering of nanocarrier systems with supra-molecular structures. Smart mesoporous silica nanoparticles (MSNs), with excellent biocompatibility, tunable physicochemical properties, and site-specific functionalization, offer efficient and high loading capacity as well as robust and targeted delivery of a variety of payloads in a controlled fashion. Such unique nanocarriers should have great potential for challenging biomedical applications, such as tissue engineering, bioimaging techniques, stem cell research, and cancer therapies. However, in vivo applications of these nanocarriers should be further validated before clinical translation. To this end, this review begins with a brief introduction of MSNs properties, targeted drug delivery, and controlled release with a particular emphasis on their most recent diagnostic and therapeutic applications.

Marine Polysaccharides for Wound Dressings Application: An Overview.

Abstract: Wound dressings have become a crucial treatment for wound healing due to their convenience, low cost, and prolonged wound management. As cutting-edge biomaterials, marine polysaccharides are divided from most marine organisms. It possesses various bioactivities, which allowing them to be processed into various forms of wound dressings. Therefore, a comprehensive understanding of the application of marine polysaccharides in wound dressings is particularly important for the studies of wound therapy. In this review, we first introduce the wound healing process and describe the characteristics of modern commonly used dressings. Then, the properties of various marine polysaccharides and their application in wound dressing development are outlined. Finally, strategies for developing and enhancing marine polysaccharide wound dressings are described, and an outlook of these dressings is given. The diverse bioactivities of marine polysaccharides including antibacterial, anti-inflammatory, haemostatic properties, etc., providing excellent wound management and accelerate wound healing. Meanwhile, these biomaterials have higher biocompatibility and biodegradability compared to synthetic ones. On the other hand, marine polysaccharides can be combined with copolymers and active substances to prepare various forms of dressings. Among them, emerging types of dressings such as nanofibers, smart hydrogels and injectable hydrogels are at the research frontier of their development. Therefore, marine polysaccharides are essential materials in wound dressings fabrication and have a promising future.

Factors Contributing to Medication Adherence in Patients with a Chronic Condition: A Scoping Review of Qualitative Research

Abstract: Introduction: Medication adherence continues to be a significant challenge in healthcare, and there is a shortage of effective interventions in this area. This scoping review studied the patient-related factors of medication adherence. Methods: We searched Medline Ovid, Scopus, and Cochrane Library from January 2009 to June 2021 to find the most recent original qualitative studies or systematic reviews that addressed the patient-related factors of medication adherence in treating chronic conditions. We used the PRISMA-ScR checklist to ensure the quality of the study. Results: The initial search revealed 4404 studies, of which we included 89 qualitative studies in the scoping review. We inductively organized the patient-related factors causing barriers, as well as the facilitators to medication adherence. The studies more often dealt with barriers than facilitators. We classified the factors as patient-specific, illness-specific, medication-related, healthcare and system-related, sociocultural, as well as logistical and financial factors. Information and knowledge of diseases and their treatment, communication, trust in patient-provider relationships, support, and adequate resources appeared to be the critical facilitators in medication adherence from the patient perspective. Discussion and conclusions: Patients are willing to discuss their concerns about medications. Better communication and better information on medicines appear to be among the critical factors for patients. The findings of this scoping review may help those who plan further interventions to improve medication adherence.

Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Abstract: Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery.

Abstract: The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

Microemulsion-Based Media in Nose-to-Brain Drug Delivery.

Abstract: Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system The most important advantage of this approach is the ability to avoid the blood-brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa These issues could be minimized by using a properly designed drug carrier Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia

Electrospun Nanofibers/Nanofibrous Scaffolds Loaded with Silver Nanoparticles as Effective Antibacterial Wound Dressing Materials

Abstract: The treatment of wounds is expensive and challenging. Most of the available wound dressings are not effective and suffer from limitations such as poor antimicrobial activity, toxicity, inability to provide suitable moisture to the wound and poor mechanical performance. The use of inappropriate wound dressings can result in a delayed wound healing process. Nanosize range scaffolds have triggered great attention because of their attractive properties, which include their capability to deliver bioactive agents, high surface area, improved mechanical properties, mimic the extracellular matrix (ECM), and high porosity. Nanofibrous materials can be further encapsulated/loaded with metal-based nanoparticles to enhance their therapeutic outcomes in wound healing applications. The widely studied metal-based nanoparticles, silver nanoparticles exhibit good properties such as outstanding antibacterial activity, display antioxidant, and anti-inflammatory properties, support cell growth, making it an essential bioactive agent in wound dressings. This review article reports the biological (in vivo and in vitro) and mechanical outcomes of nanofibrous scaffolds loaded with silver nanoparticles on wound healing.