Target-Specific Delivery and Bioavailability of Pharmaceuticals via Janus and Dendrimer Particles.

Nanosized Janus and dendrimer particles have emerged as promising nanocarriers for the target-specific delivery and improved bioavailability of pharmaceuticals. Janus particles, with two distinct regions exhibiting different physical and chemical properties, provide a unique platform for the simultaneous delivery of multiple drugs or tissue-specific targeting. Conversely, dendrimers are branched, nanoscale polymers with well-defined surface functionalities that can be designed for improved drug targeting and release. Both Janus particles and dendrimers have demonstrated their potential to improve the solubility and stability of poorly water-soluble drugs, increase the intracellular uptake of drugs, and reduce their toxicity by controlling the release rate. The surface functionalities of these nanocarriers can be tailored to specific targets, such as overexpressed receptors on cancer cells, leading to enhanced drug efficacy The design of these nanocarriers can be optimized by tuning the size, shape, and surface functionalities, among other parameters. The incorporation of Janus and dendrimer particles into composite materials to create hybrid systems for enhancing drug delivery, leveraging the unique properties and functionalities of both materials, can offer promising outcomes. Nanosized Janus and dendrimer particles hold great promise for the delivery and improved bioavailability of pharmaceuticals. Further research is required to optimize these nanocarriers and bring them to the clinical setting to treat various diseases. This article discusses various nanosized Janus and dendrimer particles for target-specific delivery and bioavailability of pharmaceuticals. In addition, the development of Janus-dendrimer hybrid nanoparticles to address some limitations of standalone nanosized Janus and dendrimer particles is discussed.

Development of Janus Particles as Potential Drug Delivery Systems for Diabetes Treatment and Antimicrobial Applications.

Janus particles have emerged as a novel and smart material that could improve pharmaceutical formulation, drug delivery, and theranostics. Janus particles have two distinct compartments that differ in functionality, physicochemical properties, and morphological characteristics, among other conventional particles. Recently, Janus particles have attracted considerable attention as effective particulate drug delivery systems as they can accommodate two opposing pharmaceutical agents that can be engineered at the molecular level to achieve better target affinity, lower drug dosage to achieve a therapeutic effect, and controlled drug release with improved pharmacokinetics and pharmacodynamics. This article discusses the development of Janus particles for tailored and improved delivery of pharmaceutical agents for diabetes treatment and antimicrobial applications. It provides an account of advances in the synthesis of Janus particles from various materials using different approaches. It appraises Janus particles as a promising particulate system with the potential to improve conventional delivery systems, providing a better loading capacity and targeting specificity whilst promoting multi-drugs loading and single-dose-drug administration.

Aptamer-Mediated Antiviral Approaches for SARS-CoV-2.

2020 and 2021 were disastrous years across the world, with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) virus as a pandemic, which continues to be a top global health issue. There are still many countries and regions struggling to fight coronavirus disease 2019 (COVID-19), and, with the emergence of the various variants of the virus, we are still far from considering this global pandemic over. In addition to having good diagnostic tools and a variety of vaccines with high efficacy, it is of utmost importance to develop effective antiviral drugs or therapies to battle COVID-19. Aptamers known as the next-generation targeting elements can offer promising opportunities in developing antiviral drugs against SARS-CoV-2. This is owing to their high specificity and affinity, making them ideal for targeting ligands and neutralizers to impede both, viral entry and replication or even further enhance the anti-infection effects in the infected host cells. Also, aptamers are extremely attractive as they can be rapidly synthesized and scalable with a lower production cost. This work provides in-depth discussions on the potential of aptamers in therapeutic applications, their mode of action, and current progress on the use of aptamer-based therapies against SARS-CoV-2 and other viruses. The article also discusses the limitations associated with aptamer-based SARS-CoV-2-antiviral therapy with several proposed ideas to resolve them. Lastly, theranostic applications of aptamer nanoformulated dendrimers against viral infections are discussed.

Secretomes as an emerging class of bioactive ingredients for enhanced cosmeceutical applications.

Skin ageing is predominantly caused by either intrinsic or extrinsic factors, leading to undesirable skin features. Advancements in both molecular and cellular fields have created possibilities in developing novel stem cell-derived active ingredients for cosmeceutical applications and the beauty industry. Mesenchymal stromal cell (MSC)-derived secretomes or conditioned media hold great promise for advancing skin repair and regeneration due to the presence of varying cytokines. These cytokines signal our cells and trigger biological mechanisms associated with anti-inflammatory, antioxidant, anti-ageing, proliferative and immunomodulatory effects. In this review, we discuss the potential of MSC secretomes as novel biomaterials for skincare and rejuvenation by illustrating their mechanism of action related to wound healing, anti-ageing and whitening properties. The advantages and disadvantages of secretomes are compared with both plant-based and animal-derived extracts. In addition, this paper reviews the current safety standards, regulations, market products and research work related to the cosmeceutical applications of secretomes along with strategies to maintain and improve the therapeutic efficacy and production of secretomes. The future outlook of beauty industry is also presented. Lastly, we highlight significant challenges to be addressed for the clinical realization of MSC secretomes-based skin therapies as well as providing perspectives for the future direction of secretomes.

Therapeutic Applications of Metal and Metal-Oxide Nanoparticles: Dermato-Cosmetic Perspectives.

Invention of novel nanomaterials guaranteeing enhanced biomedical performance in diagnostics and therapeutics, is a perpetual initiative. In this regard, the upsurge and widespread usage of nanoparticles is a ubiquitous phenomenon, focusing predominantly on the application of submicroscopic (< 100 nm) particles. While this is facilitated attributing to their wide range of benefits, a major challenge is to create and maintain a balance, by alleviating the associated toxicity levels. In this minireview, we collate and discuss particularly recent advancements in therapeutic applications of metal and metal oxide nanoparticles in skin and cosmetic applications. On the one hand, we outline the dermatological intrusions, including applications in wound healing. On the other hand, we keep track of the recent trends in the development of cosmeceuticals via nanoparticle engrossments. The dermato-cosmetic applications of metal and metal oxide nanoparticles encompass diverse aspects, including targeted, controlled drug release, and conferring ultraviolet and antimicrobial protections to the skin. Additionally, we deliberate on the critical aspects in comprehending the advantage of rheological assessments, while characterizing the nanoparticulate systems. As an illustration, we single out psoriasis, to capture and comment on the nanodermatology-based curative standpoints. Finally, we lay a broad outlook and examine the imminent prospects.

Formulation Development of a Food-Graded Curcumin-Loaded Medium Chain Triglycerides-Encapsulated Kappa Carrageenan (CUR-MCT-KC) Gel Bead Based Oral Delivery Formulation.

In recent years, curcumin has been a major research endeavor in food and biopharmaceutical industries owing to its miscellaneous health benefits. There is an increasing amount of research ongoing in the development of an ideal curcumin delivery system to resolve its limitations and further enhance its solubility, bioavailability and bioactivity. The emergence of food-graded materials and natural polymers has elicited new research interests into enhanced pharmaceutical delivery due to their unique properties as delivery carriers. The current study is to develop a natural and food-graded drug carrier with food-derived MCT oil and a seaweed-extracted polymer called k-carrageenan for oral delivery of curcumin with improved solubility, high gastric resistance, and high encapsulation of curcumin. The application of k-carrageenan as a structuring agent that gelatinizes o/w emulsion is rarely reported and there is so far no MCT-KC system established for the delivery of hydrophobic/lipophilic molecules. This article reports the synthesis and a series of in vitro bio-physicochemical studies to examine the performance of CUR-MCT-KC as an oral delivery system. The solubility of CUR was increased significantly using MCT with a good encapsulation efficiency of 73.98 ± 1.57% and a loading capacity of 1.32 ± 0.03 mg CUR/mL MCT. CUR was successfully loaded in MCT-KC, which was confirmed using FTIR and SEM with good storage and thermal stability. Dissolution study indicated that the solubility of CUR was enhanced two-fold using heated MCT oil as compared to naked or unformulated CUR. In vitro release study revealed that encapsulated CUR was protected from premature burst under simulated gastric environment and released drastically in simulated intestinal condition. The CUR release was active at intestinal pH with the cumulative release of >90% CUR after 5 h incubation, which is the desired outcome for CUR absorption under human intestinal conditions. A similar release profile was also obtained when CUR was replaced with beta-carotene molecules. Hence, the reported findings demonstrate the potencies of MCT-KC as a promising delivery carrier for hydrophobic candidates such as CUR.

Engineered Aptamers for Enhanced COVID-19 Theranostics.

INTRODUCTION: The 2019-novel coronavirus disease (COVID-19) is an intractable global health challenge resulting in an aberrant rate of morbidity and mortality worldwide. The mode of entry for SARS-CoV-2 into host cells occurs through clathrin-mediated endocytosis. As part of the efforts to mitigate COVID-19 infections, rapid and accurate detection methods, as well as smart vaccine and drug designs with SARS-CoV-2 targeting capabilities are critically needed. This systematic review aimed to present a good mapping between the structural and functional characteristics of aptamers and their potential applications in COVID-19 theranostics. METHODS: In this study, extensive discussions into the potential development of aptameric systems as robust theranostics for rapid mitigation of the virulent SARS-CoV-2 was made. Information required for this study were extracted from a systematic review of literature in PubMed, SCOPUS, Web of Science (WOS), and other official related reports from reputable organisations. RESULTS: The global burden of COVID-19 pandemic was discussed including the progress in rapid detection, repurposing of existing antiviral drugs, and development of prophylactic vaccines. Aptamers have highly specific and stable target binding characteristics which can be generated and engineered with less complexity for COVID-19 targeted theranostic applications. CONCLUSIONS: There is an urgent need to develop safe innovative biomedical technologies to mitigate the dire impact of COVID-19 on public health worldwide. Research advances into aptameric systems bode well with the fact that they can be engineered for the development of effective and affordable diagnostics, therapeutics and prophylactic vaccines for SARS-CoV-2 and other infectious pathogens.

Developing Nano-Delivery Systems for Agriculture and Food Applications with Nature-Derived Polymers.

The applications of nanotechnology are wide ranging, and developing functional nanomaterials for agri-food applications from nature-derived polymers is widely conceived as a sustainable approach that is safer for human and animal consumption. In light of this, this review focuses on the advances in the development of nano-delivery systems using nature-derived polymers for agri-food applications. The review opens with a section detailing the different types of nature-derived polymers currently being used in various applications in the agri-food industry with a special mention on microbial extracellular polymeric materials. The major applications of nano-delivery systems in the food sector, such as food fortification and food preservation, as well as in the agricultural sector for controlled release of agrochemicals using nature-derived polymers are discussed. The review ends with a perspective on the safety and public perception of nano-enabled foods with a concluding remark on future directions of incorporating nano-delivery systems for agri-food purposes.

Prospects of kefiran as a food-derived biopolymer for agri-food and biomedical applications.

There is a huge demand for food-derived polysaccharides in the field of materials research due to the increasing concerns posed by synthetic biopolymers. The scientific community is extensively searching for other natural, food-derived or bio-inspired polymers that possess promising potentials and advantageous properties that can be promptly utilized for multifarious applications. Kefiran, a food-derived microbial exopolysaccharide extracted from kefir grains has exhibited evidence of non-toxicity, anti-microbial activity, nutritional value, and other favourable characteristics. This review aims to shed light on the properties of kefiran and provide an overview of its applications in the agri-food and biomedical sectors. The present work also discusses the challenges and prospects that lie ahead for kefiran in finding its place amongst the existing spectrum of natural and biodegradable polymers.

Aptamers: an emerging class of bioaffinity ligands in bioactive peptide applications.

The food and health applications of bioactive peptides have grown remarkably in the past few decades. Current elucidations have shown that bioactive peptides have unique structural arrangement of amino acids, conferring distinct functionalities, and molecular affinity characteristics. However, whereas interest in the biological potency of bioactive peptides has grown, cost-effective techniques for monitoring the structural changes in these peptides and how these changes affect the biological properties have not grown at the same rate. Due to the high binding affinity of aptamers for other biomolecules, they have a huge potential for use in tracking the structural, conformational, and compositional changes in bioactive peptides. This review provides an overview of bioactive peptides and their essential structure-activity relationship. The review further highlights on the types and methods of synthesis of aptamers before the discussion of the prospects, merits, and challenges in the use of aptamers for bioaffinity interactions with bioactive peptides.

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications-The Role of Molecular Dynamics Simulation.

Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non-targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer-target binding results from several inter-molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer-mediated receptor targeting in targeted cancer therapy. MD simulation offers real-time analysis of the molecular drivers of the aptamer-receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.

Binding Characterization of Aptamer-Drug Layered Microformulations and In Vitro Release Assessment.

Efficient delivery of adequate active ingredients to targeted malignant cells is critical, attributing to recurrent biophysical and biochemical challenges associated with conventional pharmaceutical delivery systems. These challenges include drug leakage, low targeting capability, high systemic cytotoxicity, and poor pharmacokinetics and pharmacodynamics. Targeted delivery system is a promising development to deliver sufficient amounts of drug molecules to target cells in a controlled release pattern mode. Aptameric ligands possess unique affinity targeting capabilities which can be exploited in the design of high pay-load drug formulations to navigate active molecules to the malignant sites. This study focuses on the development of a copolymeric and multifunctional drug-loaded aptamer-conjugated poly(lactide-co-glycolic acid)-polyethylenimine (PLGA-PEI) (DPAP) delivery system, via a layer-by-layer synthesis method, using a water-in-oil-in-water double emulsion approach. The binding characteristics, targeting capability, biophysical properties, encapsulation efficiency, and drug release profile of the DPAP system were investigated under varying conditions of ionic strength, polymer composition and molecular weight (MW), and degree of PEGylation of the synthetic core. Experimental results showed increased drug release rate with increasing buffer ionic strength. DPAP particulate system obtained the highest drug release of 50% at day 9 at 1 M NaCl ionic strength. DPAP formulation, using PLGA 65:35 and PEI MW of ∼800 Da, demonstrated an encapsulation efficiency of 78.93%, and a loading capacity of 0.1605 mg bovine serum albumin per mg PLGA. DPAP (PLGA 65:35, PEI MW∼25 kDa) formulation showed a high release rate with a biphasic release profile. Experimental data depicted a lower targeting power and reduced drug release rate for the PEGylated DPAP formulations. The outcomes from the present study lay the foundation to optimize the performance of DPAP system as an effective synthetic drug carrier for targeted delivery.

Cardiovascular therapies utilizing targeted delivery of nanomedicines and aptamers.

Cardiovascular ailments are the foremost trigger of death in the world today, including myocardial infarction and ischemic heart diseases. To date, extraordinary measures have been prescribed, from the perspectives of both conventional medical therapies and surgeries, to enforce cardiac cell regeneration post cardiac traumas, albeit with limited long-term success. The prospects of successful heart transplants are also grim, considering exorbitant costs and unavailability of suitable donors in most cases. From the perspective of cardiac revascularization, use of nanoparticles and nanoparticle mediated targeted drug delivery have garnered substantial attention, attributing to both active and passive heart targeting, with enhanced target specificity and sensitivity. This review focuses on this aspect, while outlining the progress in targeted delivery of nanomedicines in the prognosis and subsequent therapy of cardiovascular disorders, and recapitulating the benefits and intrinsic challenges associated with the incorporation of nanoparticles. This article categorically provides an overview of nanoparticle-mediated targeted delivery systems and their implications in handling cardiovascular diseases, including their intrinsic benefits and encountered procedural trials and challenges. Additionally, the solicitations of aptamers in targeted drug delivery with identical objectives, are presented. This includes a detailed appraisal on various aptamer-navigated nanoparticle targeted delivery platforms in the diagnosis and treatment of cardiovascular maladies. Despite a few impending challenges, subject to additional investigations, both nanoparticles as well as aptamers show a high degree of promise, and pose as the next generation of drug delivery vehicles, in targeted cardiovascular therapy.

Prospects in the use of aptamers for characterizing the structure and stability of bioactive proteins and peptides in food.

Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.

An overview of the characteristics of the novel avian influenza A H7N9 virus in humans.

The novel avian influenza A H7N9 virus which caused the first human infection in Shanghai, China; was reported on the 31st of March 2013 before spreading rapidly to other Chinese provinces and municipal cities. This is the first time the low pathogenic avian influenza A virus has caused human infections and deaths; with cases of severe respiratory disease with pneumonia being reported. There were 440 confirmed cases with 122 fatalities by 16 May 2014; with a fatality risk of ∼28%. The median age of patients was 61 years with a male-to-female ratio of 2.4:1. The main source of infection was identified as exposure to poultry and there is so far no definitive evidence of sustained person-to-person transmission. The neuraminidase inhibitors, namely oseltamivir, zanamivir, and peramivir; have shown good efficacy in the management of the novel H7N9 virus. Treatment is recommended for all hospitalized patients, and for confirmed and probable outpatient cases; and should ideally be initiated within 48 h of the onset of illness for the best outcome. Phylogenetic analysis found that the novel H7N9 virus is avian in origin and evolved from multiple reassortments of at least four origins. Indeed the novel H7N9 virus acquired human adaptation via mutations in its eight RNA gene segments. Enhanced surveillance and effective global control are essential to prevent pandemic outbreaks of the novel H7N9 virus.