Effects of pellet starch levels in automatic milking systems on rumen fermentation, plasma metabolites, and milk production in mid-lactation cows.

The aim of this study was to evaluate whether the starch levels in pellets fed to cows in automatic milking systems (AMS) affect subacute ruminal acidosis (SARA) occurrence and metabolite parameters. Twenty-four lactating cows (124.4 ± 49.9 days in milk) were studied in a crossover design with two periods of 21 days each and two treatment groups-a control group fed AMS pellets containing 30.0% of starch dry matter (DM) and an experimental group fed AMS pellets containing 23.5% of starch DM. All cows received the same partial mixed ration (PMR). The 1-hr mean ruminal pH in both groups decreased over 4 hr after feeding on PMR but recovered by the next morning. The ruminal pH was unaffected by either treatment, and both groups developed SARA. The groups had no significant differences in the concentrations of ruminal volatile fatty acids, lipopolysaccharides, plasma acute-phase proteins, other metabolites, and hormones. The milk yield and composition were not different in both groups. Feeding low-starch pellets in the AMS did not contribute to the risk of SARA occurrence in cows and had no additive effects on rumen fermentation, plasma metabolites, or milk production.

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.

Effect of anti-lipopolysaccharide of Escherichia coli antibody feeding for Holstein calves on ruminal lipopolysaccharide activity and plasma metabolites concentrations during pre- and post-weaning periods.

This study was performed to examine the effects of anti- lipopolysaccharide (LPS) of Escherichia coli chicken egg Yolk immunoglobulin (IgY) provided to calves for 7 weeks during the pre- and post-weaning periods on rumen LPS activity, plasma acute phase protein (APP) concentrations, and metabolic parameters. A total of 30 Holstein calves were randomly assigned to two groups of 15 each: an IgY group fed Anti-E. coli LPS IgY, and a control group fed whole egg powder as a placebo. The study was conducted on calves aged 3-10 weeks, weaned at 7 weeks. The ruminal LPS activity of the IgY group was approximately 60% lower than the control group at 10 weeks of age. Plasma APP and cytokine concentrations in the IgY group did not differ from those in the control group. The daily weight gain in the IgY group was significantly higher than the control group for the whole experimental period. Plasma albumin/globulin was lower (P<0.05), and plasma aspartate transferase concentration was higher (P<0.05) in the IgY group than in the control group during the experimental period. In conclusion, feeding Anti-E. coli LPS IgY for 7 weeks pre- and post-weaning remarkably reduced the rumen LPS activity and improved the daily weight gain. The impact of Anti-E. coli LPS IgY on LPS activities in the lower gastrointestinal tract, and elucidation as to the mechanism responsible for the improvement in daily weight gain require further investigation.

Leveraging Public Data to Predict Global Niches and Distributions of Rhizostome Jellyfishes.

As climate change progresses rapidly, biodiversity declines, and ecosystems shift, it is becoming increasingly difficult to document dynamic populations, track fluctuations, and predict responses to climate change. Concurrently, publicly available databases and tools are improving scientific accessibility, increasing collaboration, and generating more data than ever before. One of the most successful projects is iNaturalist, an AI-driven social network doubling as a public database designed to allow citizen scientists to report personal biodiversity reports with accuracy. iNaturalist is especially useful for the research of rare, dangerous, and charismatic organisms, but requires better integration into the marine system. Despite their abundance and ecological relevance, there are few long-term, high-sample datasets for jellyfish, which makes management difficult. To provide some high-sample datasets and demonstrate the utility of publicly collected data, we synthesized two global datasets for ten genera of jellyfishes in the order Rhizostomeae containing 8412 curated datapoints from both iNaturalist (n = 7807) and the published literature (n = 605). We then used these reports in conjunction with publicly available environmental data to predict global niche partitioning and distributions. Initial niche models inferred that only two of ten genera have distinct niche spaces; however, the application of machine learning-based random forest models suggests genus-specific variation in the relevance of abiotic environmental variables used to predict jellyfish occurrence. Our approach to incorporating reports from the literature with iNaturalist data helped evaluate the quality of the models and, more importantly, the quality of the underlying data. We find that free, accessible online data is valuable, yet subject to biases through limited taxonomic, geographic, and environmental resolution. To improve data resolution, and in turn its informative power, we recommend increasing global participation through collaboration with experts, public figures, and hobbyists in underrepresented regions capable of implementing regionally coordinated projects.

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.

Oncological Ligand-Target Binding Systems and Developmental Approaches for Cancer Theranostics.

Targeted treatment of cancer hinges on the identification of specific intracellular molecular receptors on cancer cells to stimulate apoptosis for eventually inhibiting growth; the development of novel ligands to target biomarkers expressed by the cancer cells; and the creation of novel multifunctional carrier systems for targeted delivery of anticancer drugs to specific malignant sites. There are numerous receptors, antigens, and biomarkers that have been discovered as oncological targets (oncotargets) for cancer diagnosis and treatment applications. Oncotargets are critically important to navigate active anticancer drug ingredients to specific disease sites with no/minimal effect on surrounding normal cells. In silico techniques relating to genomics, proteomics, and bioinformatics have catalyzed the discovery of oncotargets for various cancer types. Effective oncotargeting requires high-affinity probes engineered for specific binding of receptors associated with the malignancy. Computational methods such as structural modeling and molecular dynamic (MD) simulations offer opportunities to structurally design novel ligands and optimize binding affinity for specific oncotargets. This article proposes a streamlined approach for the development of ligand-oncotarget bioaffinity systems via integrated structural modeling and MD simulations, making use of proteomics, genomic, and X-ray crystallographic resources, to support targeted diagnosis and treatment of cancers and tumors.

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.

Atomistic probing of aptameric binding of CD19 outer membrane domain reveals an "aptamer walking" mechanism.

We propose an integrated structural approach to search potential aptamer molecules for targeting cancer receptor proteins. We used the outer cellular domain of the B-lymphocyte antigen, CD19, as the target for this study. First, using available protein-aptamer structures deposited in the protein data bank as resources, structural annotation was performed to seek the most probable binding aptamer and its potential initial configuration to the CD19 structure. Using this initial structure, molecular dynamics (MD) simulations were performed for adjustment of the aptamer-binding. During this process, we observed an "aptamer walking" mechanism of the binding of the single-stranded RNA-aptamer to CD19: the aptamer molecule gradually adjusts its configurations and shifts toward favorable binding positions. However, the target molecule CD19 maintained a relatively stable conformation during this process. The interface area between the RNA-aptamer and CD19 increased from less than 8 nm2 to over 12 nm2 during a 2-µs MD simulation. Using a stable binding pose as the starting structure, we manually mutated the RNA-aptamer to a DNA-aptamer and found that the interface area was further increased to over 16 nm2 , indicating a stronger affinity compared to the RNA-aptamer. The RNA- and DNA-aptamers and their stable binding-poses to the CD19 molecule may be used as templates in designing potential aptamer molecules that target the B-cell marker molecule CD19 with enhanced specificity and stability.

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.

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.

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.

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.

Process evaluation and in vitro selectivity analysis of aptamer-drug polymeric formulation for targeted pharmaceutical delivery.

Targeted drug delivery is a promising strategy to promote effective delivery of conventional and emerging pharmaceuticals. The emergence of aptamers as superior targeting ligands to direct active drug molecules specifically to desired malignant cells has created new opportunities to enhance disease therapies. The application of biodegradable polymers as delivery carriers to develop aptamer-navigated drug delivery system is a promising approach to effectively deliver desired drug dosages to target cells. This study reports the development of a layer-by-layer aptamer-mediated drug delivery system (DPAP) via a w/o/w double emulsion technique homogenized by ultrasonication or magnetic stirring. Experimental results showed no significant differences in the biophysical characteristics of DPAP nanoparticles generated using the two homogenization techniques. The DPAP formulation demonstrated a strong targeting performance and selectivity towards its target receptor molecules in the presence of non-targets. The DPAP formulation demonstrated a controlled and sustained drug release profile under the conditions of pH 7 and temperature 37 °C. Also, the drug release rate of DPAP formulation was successfully accelerated under an endosomal acidic condition of ∼pH 5.5, indicating the potential to enhance drug delivery within the endosomal micro-environment. The findings from this work are useful to understanding polymer-aptamer-drug relationship and their impact on developing effective targeted delivery systems.

Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.

BACKGROUND: The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. OBJECTIVE: The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. RESULTS: This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. CONCLUSION: A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with stage-wise delivery mechanism is presented to illustrate the potential efficacy of aptamer- polymer cargos for enhanced cell targeting and drug delivery.