Tool For Delivery Research Articles

Morin loaded mesoporous molecular sieves as novel devices to the potential treatment of tumor pathologies.

Morin is an antioxidant and anticancer flavonoid, extracted from natural sources, that may exert beneficial effects for several pathologies. Despite this, the administration of morin represents a challenge due to its low aqueous solubility. Mesoporous silica materials have emerged as biocompatible tools for drug delivery, as their pore size can be modulated for maximum surface area to volume ratio. In this contribution, we evaluate the ability of iron-modified mesoporous materials, for morin loading and controlled delivery. The SBA-15 and MCM-41 sieves were synthesized and modified with iron (metal content 4.02 and 6.27 % wt, respectivily). Characterization by transmission electron microscopy, XRD and UV-Vis revealed adequate pore size and agglomerates of very small metallic nanospecies (nanoclusters), without larger iron oxide nanoparticles. FT-IR spectra confirmed the presence of silanol groups in the solid hosts, which can interact with different groups present in morin molecules. SBA-15 materials were more efficient in terms of morin loading capacity (LC) due to their larger pore diameter. LC was more than 35% for SBA-15 materials when adsorptions studies were carried out with 9mg of drug. Antioxidant activity were assayed by using DPPH test. Free iron materials presented a significate improvement as antioxidants after morin incorporation, reaching a scavenging activity of almost a 90%. On the other hand, in iron modified mesoporous materials, the presence of morin did not affect the scavenging activity. The results could be related with the formation of a complex between the flavonoid and the iron. Finally, biosafety studies using normal epithelial cells revealed that neither the loaded nor the unloaded materials exerted toxicity, even at doses of 1mg/ml. These findings expand knowledge about mesoporous materials as suitable carriers of flavonoids with the aim of improving therapies for a wide range of pathologies.

Economics Teachers' Integration of ICT for Enhanced Economics Curriculum Implementation

Information and communication technology (ICT) has gained tremendous attention as a tool for instructional delivery and assessment. However, high school Economics teachers have yet to fully utilize this educational tool to implement the Economics curriculum effectively. Information and communication technology enables teachers to communicate with learners outside the physical classroom, encourages learner engagement, facilitates differentiated teaching, simplifies abstract concepts, and helps teachers design, distribute and provide immediate assessment feedback. Nevertheless, there is sparse research on Economics teachers' integration of ICT to enhance Economics curriculum implementation in South Africa. This empirical study explores Economics teachers' ICT integration to enhance Economics curriculum implementation. Mediated learning experience (MLE) was the theoretical framework which guided this study. A qualitative approach was used in this study. Three teachers from three different research sites were purposefully selected for the study. Using a case study design, data were obtained through semi-structured interviews and classroom observations. The study findings reveal that the teachers in this study were utilizing ICT to enhance their teaching. However, there is still room for improvement in teachers' ICT integration. The study recommends continuous teacher development on ICT integration to enhance economics curriculum implementation.

MANUFACTURING A NEW MEDICATED CHEWABLE GUM FROM NATURAL MATERIALS TO CONTROL PERIODONTAL PATHOGENS

Within their multispecies subgingival biofilm in deep pockets, periodontal pathogens are being protected from the attendance of antimicrobial agents, in addition to; the licensed safe concentrations of antibacterials are less effective against biofilm; which leads to unsuccessful treatment and recurrent infections. Therefore, as a first local effort, the medical aim of the present study was to apply the natural material, frankincense, to make a medical chewing gum and an intra-pocket antimicrobial delivery system as a hopeful solution for the ineffectiveness of antimicrobials to control periodontal pathogens. The ability of frankincense film to work as an antibiotic delivery tool was tested by agar diffusion procedure against three types of anaerobic pathogens isolated from periodontal pockets. The usefulness of the currently prepared medical chewing gum from frankincense and other natural additives to control periodontal infections was tested by measuring the level of bacterial hydrolytic enzymes in gingival pockets. The results proved the validity of frankincense film to be a natural delivery tool of antimicrobial ingredients by the denotation of inhibiting the growth on agar plate. The results also proved the validity of frankincense to formulate a medical chewable gum with profound efficiency in reducing the bacterial load inside the gingival tissues. The study claims for the practical application of frankincense in the field of medicines production as a gum base to produce a medical chewable gum and an antimicrobial delivery system. This application can be adopted by pharmaceutical factories and can be dependable by the Ministry of Health and dentists as an alternative to increasing the concentration or combination of chemical medicines

Quantum Dot-based Bio-conjugates as an Emerging Bioimaging Tool for Cancer Theranostic- A Review.

Cancer is the most widely studied disorder in humans, but proper treatment has not yet been developed for it. Conventional therapies, like chemotherapy, radiation therapy, and surgery, have been employed. Such therapies target not only cancerous cells but also harm normal cells. Conventional therapy does not result in specific targeting and hence leads to severe side effects. The main objective of this study is to explore the QDs. QDs are used as nanocarriers for diagnosis and treatment at the same time. They are based on the principle of theranostic approach. QDs can be conjugated with antibodies via various methods that result in targeted therapy. This results in their dual function as a diagnostic and therapeutic tool. Nanotechnology involving such nanocarriers can increase the specificity and reduce the side effects, leaving the normal cells unaffected. This review pays attention to different methods for synthesising QDs. QDs can be obtained using either organic method and synthetic methods. It was found that QDs synthesised naturally are more feasible than the synthetic process. Top or bottom-up approaches have also emerged for the synthesis of QDs. QDs can be conjugated with an antibody via non-covalent and covalent binding. Covalent binding is much more feasible than any other method. Zero-length coupling plays an important role as EDC (1-Ethyl-3-Ethyl dimethylaminopropyl)carbodiimide is a strong crosslinker and is widely used for conjugating molecules. Antibodies work as surface ligands that lead to antigen- antibody interaction, resulting in site-specific targeting and leaving behind the normal cells unaffected. Cellular uptake of the molecule is done by either passive targeting or active targeting. QDs are tiny nanocrystals that are inorganic in nature and vary in size and range. Based on different sizes, they emit light of specific wavelengths. They have their own luminescent and optical properties that lead to the monitoring, imaging, and transport of the therapeutic moiety to a variety of targets in the body. The surface of the QDs is modified to boost their functioning. They act as a tool for diagnosis, imaging, and delivery of therapeutic moieties. For improved therapeutic effects, nanotechnology leads the cellular uptake of nanoparticles via passive targeting or active targeting. It is a crucial platform that not only leads to imaging and diagnosis but also helps to deliver therapeutic moieties to specific sites. Therefore, this review concludes that there are numerous drawbacks to the current cancer treatment options, which ultimately result in treatment failure. Therefore, nanotechnology that involves such a nanocarrier will serve as a tool for overcoming all limitations of the traditional therapeutic approach. This approach helps in reducing the dose of anticancer agents for effective treatment and hence improving the therapeutic index. QDs can not only diagnose a disease but also deliver drugs to the cancerous site.

Development of cationic solid lipid nanoparticles incorporating cholesteryl-9-carboxynonanoate (9CCN) for delivery of antagomiRs to macrophages

Lipid-based nanoparticles are a useful tool for nucleic acids delivery and have been regarded as a promising approach for diverse diseases. However, off-targets effects are a matter of concern and some strategies to improve selectivity of solid lipid nanoparticles (SLNs) were reported. The goal of this study was to test formulations of SLNs incorporating lipid cholesteryl-9-carboxynonanoate (9CCN) as “eat-me” signal to target antagomiR oligonucleotides to macrophages. We formulate four SLNs, and those with a mean diameter of 200 nm and a Z-potential values between 25 and 40 mV, which allowed the antagomiR binding, were selected for in vitro studies. Cell viability, transfection efficiency and cellular uptake assays were performed within in vitro macrophages using flow cytometry and confocal imaging and the SLNs incorporating 25 mg of 9CCN proved to be the best formulation. Subsequently, we used a labeled antagomiR to study tissue distribution in in-vivo ApoE-/- model of atherosclerosis. Using the ApoE-/- model we demonstrated that SLNs with phagocytic signal 9-CCN target macrophages and release the antagomiR cargo in a selective way.

Healthcare Capacity Building in Northwest Syria: Challenges, Successes, and Lessons Learned

The conflict in Syria has caused significant loss of life and widespread displacement. Northwest Syria (NWS) has been heavily impacted, leading to challenges in providing healthcare services. Attacks on healthcare workers and facilities have worsened the situation. Healthcare students and professionals have been specifically targeted, disrupting their education and resulting in migration and a shortage of skilled healthcare workers. To address these challenges, local and international organizations and institutions have supported long-term projects to improve healthcare facilities and provide a trained healthcare workforce. Collaborations with multiple stakeholders have been established to ensure comprehensive and effective training opportunities, enabling healthcare workers to better serve the population's healthcare needs. A range of undergraduate, postgraduate, and research programs have been developed to enhance healthcare capacity building. These programs aim to strengthen the knowledge and skills of healthcare professionals in NWS. Efforts have been made to strengthen the health system and build the capacity of policy makers in utilizing evidence-based knowledge for informed policy decisions. Global and regional partnerships, along with adequate funding, have played a significant role in the successful enhancement of capacity building activities at all levels.
 Building healthcare and health research capacity in underdeveloped and conflict-affected parts of NWS presents numerous challenges. Underdeveloped infrastructure, inadequate teaching and service delivery tools, gender disparities, and the sustainability of funding create obstacles to effective capacity building. The political context, coupled with security concerns further complicate efforts. The accreditation of education, and the brain drain of skilled healthcare professionals, add to the difficulties in strengthening the healthcare system in NWS. Addressing these challenges requires comprehensive and collaborative approaches that prioritize stability, security, gender equity, sustainable funding, and improved coordination and resources for education and service delivery. The lessons learned from capacity-building efforts in the Syrian conflict have broader implications for other regions facing similar challenges.

Nature-inspired peptide of MtDef4 C-terminus tail enables protein delivery in mammalian cells

Cell-penetrating peptides show promise as versatile tools for intracellular delivery of therapeutic agents. Various peptides have originated from natural proteins with antimicrobial activity. We investigated the mammalian cell-penetrating properties of a 16-residue peptide with the sequence GRCRGFRRRCFCTTHC from the C-terminus tail of the Medicago truncatula defensin MtDef4. We evaluated the peptide’s ability to penetrate multiple cell types. Our results demonstrate that the peptide efficiently penetrates mammalian cells within minutes and at a micromolar concentration. Moreover, upon N-terminal fusion to the fluorescent protein GFP, the peptide efficiently delivers GFP into the cells. Despite its remarkable cellular permeability, the peptide has only a minor effect on cellular viability, making it a promising candidate for developing a cell-penetrating peptide with potential therapeutic applications.

Transmembrane modification of tumor vascular targeting peptide A7R as molecular cargo delivery tool

In recent years, targeting tumor angiogenesis has emerged as a prominent research focus in the treatment and prevention of tumor expansion. A7R (ATWLPPR) exhibits high affinity and specificity for VEGFR-2, which is overexpressed in various tumors. To enhance the tumor tissue and cell penetration capabilities of A7R, we substituted its non-critical amino acid with Arginine (R) and Glutamic acid (E), cyclized the mutant peptide, and linked it to the membrane permeation sequence using coordination principles. We designed and synthesized fifteen novel penetrating peptides that target tumor blood vessels and cells, followed by conducting various biological evaluations and cell imaging experiments. The results demonstrated that Cyclo-A7R-RRR and A7R-RLLRLLR exhibited excellent permeability towards tumor cells, with Cyclo-A7R-RRR showing superior serum stability compared to A7R. Furthermore, the modified peptides showed no toxicity towards HeLa cells, U251 cells, HuH-7 cells, and HEK293 cells under 10 μmol/L. Utilizing Cyclo-A7R-RRR or A7R-RLLRLLR for transmembrane delivery of drug molecules could significantly improve their efficacy. Our findings broaden the potential application scenarios of A7R in targeted tumor angiogenesis.

Extracellular Vesicles in Therapeutics: A Comprehensive Review on Applications, Challenges, and Clinical Progress.

Small Extracellular Vesicles (sEVs) are typically 30-150 nm in diameter, produced inside cells, and released into the extracellular space. These vesicles carry RNA, DNA, proteins, and lipids that reflect the characteristics of their parent cells, enabling communication between cells and the alteration of functions or differentiation of target cells. Owing to these properties, sEVs have recently gained attention as potential carriers for functional molecules and drug delivery tools. However, their use as a therapeutic platform faces limitations, such as challenges in mass production, purity issues, and the absence of established protocols and characterization methods. To overcome these, researchers are exploring the characterization and engineering of sEVs for various applications. This review discusses the origins of sEVs and their engineering for therapeutic effects, proposing areas needing intensive study. It covers the use of cell-derived sEVs in their natural state and in engineered forms for specific purposes. Additionally, the review details the sources of sEVs and their subsequent purification methods. It also outlines the potential of therapeutic sEVs and the requirements for successful clinical trials, including methods for large-scale production and purification. Finally, we discuss the progress of ongoing clinical trials and the implications for future healthcare, offering a comprehensive overview of the latest research in sEV applications.

Effects on visual basic programming instructional delivery using web-based tools for students’ interest and academic achievement in universities, Nigeria

AbstractThis research work ascertained the effect of Visual Basic (VBasic) Programming Instructional Delivery using Web-Based Tools on Students’ Interest and Academic Achievement in Universities in Nigeria. The purpose of the study is to determine the effect of Visual Basic (VBasic) Programming Instructional Delivery using Web-Based Tools on Students’ Interest and Academic Achievement in Universities in Nigeria. The study embraced a quasi-experimental research design. The respondent for this study comprised 74 students in year two of Alex Ekwueme Federal University, Ndu-ufu Alike and Ebonyi State University, Abakaliki. For the fact that the population is small and manageable, the entire population were studied. Researchers used VBasic Programming Achievement Test (VBPAT) instrument developed to collect data. Visual Basic Achievement Test contained 50-item questions with letter A to D options for each interest scale were used for data collection. The reliability was tested using Cronbach’s Alpha. To ensure consistency and integrity, lecturers in the study area. The researchers trained the lecturers on how to distribute the instrument for both the experiment and control groups in order to ensure homogeneous instruction. The lecturers taught the experimental group using the utilization of a web-based approach and the control group using the conventional approach. Scores generated from the experimental test using Visual Basic programming Achievement Test (V + B + PAT), were analysed using mean and analysis of covariance (ANCOVA) for answering research questions and to test hypotheses respectively at 0.5 level of significance with the aid of statistical package for social science (SPSS) version 20. The outcome of this study on research question on influence of location on the students’ academic achievement mean gain in Vbasic programming language when taught using web-based tool, showed that with the use of web-based tool in the instructional delivery of VBasic programming language brought about better improvement in students’ academic achievement. Furthermore, the outcomes of hypothesis tested showed that location is significant source of different in mean achievement scores for students taught with Visual Basic Programming language using web-based approach and visual basic programming using conventional approach. This study has implications for facilitators, learners, curriculum planners, ministries in Education among others. This study found out among others that the facilitators use web-based tools in distance education for quiz, assessment, examinations, and instructional delivery of Vbasic programming language to a less extent in Nigerian Universities. It was concluded therefore, that conventional method is less effective than web-based approach in improving student’s achievement in Visual Basic Programming. Hence Nigerian Universities should adopt the use of web-based approach in computer programming lecturers.

Inhibition of mevalonate pathway by macrophage-specific delivery of atorvastatin prevents their pro-inflammatory polarisation.

Adjustment of the cellular metabolism of pro-inflammatory macrophages is essential for their bactericidal function; however, it underlies the development of many human diseases if induced chronically. Therefore, intervention of macrophage metabolic polarisation has been recognised as a potent strategy for their treatment. Although many small-molecule inhibitors affecting macrophage metabolism have been identified, their in vivo administration requires a tool for macrophage-specific delivery to limit their potential side effects. Here, we establish Drosophila melanogaster as a simple experimental model for in vivo testing of macrophage-specific delivery tools. We found that yeast-derived glucan particles (GPs) are suitable for macrophage-specific delivery of small-molecule inhibitors. Systemic administration of GPs loaded with atorvastatin, the inhibitor of hydroxy-methyl-glutaryl-CoA reductase (Hmgcr), leads to intervention of mevalonate pathway specifically in macrophages, without affecting HMGCR activity in other tissues. Using this tool, we demonstrate that mevalonate pathway is essential for macrophage pro-inflammatory polarisation and individual's survival of infection.

A37 POSTBIOTIC BACTERIAL MEMBRANE VESICLES FROM B. SUBTILIS DELIVER NOD2 LIGANDS AND PROMOTE IN VITRO WOUND RE-EPITHLIALIZATION THROUGH RIPK2 SIGNALING

Abstract Background Bacterial membrane vesicles (MVs) are bilipid nanoparticles secreted as a conserved method of intercellular communication. MVs from Gram-positive bacteria carry diverse bacterial products and represent a unique opportunity in the growing field of postbiotics. This native machinery for mediating microbe-host interactions makes MVs a promising tool for intestinal drug delivery in the context of Crohn’s disease (CD). CD is a chronic inflammatory bowel disease characterized by relapsing inflammation of the digestive tract. CD is associated with (1) loss of function mutations in the host gene encoding the nuclear-binding oligomerization domain 2 (NOD2) pattern recognition receptor and (2) a gut microbiome with reduced capabilities to generate NOD2 stimulating muropeptides from peptidoglycan. Nod2-/- mice have decreased barrier integrity and impaired epithelial restitution upon challenge. However, there are currently no therapeutic strategies targeting NOD2 for CD management. Aims The aims of this study were to (1) leverage MVs as a biological system for NOD2 ligand delivery to intestinal epithelial cells and (2) determine the roll of probiotic MVs and bacterial ligand synergy in wound re-epithelialization. Methods MVs were purified from B. subtilis through filtration and ultracentrifugation. MVs were characterized through nanoparticle tracking analysis using NanoSight300. WT and NOD2-/- HCT116 cells, a human colorectal carcinoma cell line, were utilized for IL-8 secretion quantification by ELISA, gene expression by qPCR, and in vitro scratch wound assay by Incucyte quantification. Results Here, we demonstrate for the first time that MVs from B. subtilis deliver NOD2 ligands in vitro. Treatment with isolated MVs induces IL8 secretion and CXCL1 expression in a NOD2-dependent manner. Furthermore, MVs promote re-epithelialization after in vitro scratch wounding. This effect was completely blunted by the addition of an inhibitor for RIPK2, a downstream transducer required for NOD2 signaling. Through bacterial pathogen-associated molecular patterns (PAMPs) screening, we found that wound re-epithelialization is promoted by PAMP synergy but dependent on RIPK2 signaling. Conclusions This work suggests that delivery of muropeptides by probiotic-derived MVs is a promising strategy to promote epithelial regeneration during injury through targeting NOD2. Future directions will work towards validating these findings in human ileal primary cells and murine models of intestinal injury. Funding Agencies CIHRMedicine by Design

3D and 4D printing of biomedical materials: current trends, challenges, and future outlook

Three-dimensional (3D) and four-dimensional (4D) printing have emerged as the next-generation fabrication technologies, covering a broad spectrum of areas, including construction, medicine, transportation, and textiles. 3D printing, also known as additive manufacturing (AM), allows the fabrication of complex structures with high precision via a layer-by-layer addition of various materials. On the other hand, 4D printing technology enables printing smart materials that can alter their shape, properties, and functions upon a stimulus, such as solvent, radiation, heat, pH, magnetism, current, pressure, and relative humidity (RH). Myriad of biomedical materials (BMMs) currently serve in many biomedical engineering fields aiding patients’ needs and expanding their life-span. 3D printing of BMMs provides geometries that are impossible via conventional processing techniques, while 4D printing yields dynamic BMMs, which are intended to be in long-term contact with biological systems owing to their time-dependent stimuli responsiveness. This review comprehensively covers the most recent technological advances in 3D and 4D printing towards fabricating BMMs for tissue engineering, drug delivery, surgical and diagnostic tools, and implants and prosthetics. In addition, the challenges and gaps of 3D and 4D printed BMMs, along with their future outlook, are also extensively discussed. The current review also addresses the scarcity in the literature on the composition, properties, and performances of 3D and 4D printed BMMs in medical applications and their pros and cons. Moreover, the content presented would be immensely beneficial for material scientists, chemists, and engineers engaged in AM manufacturing and clinicians in the biomedical field. Graphical abstract. 3D and 4D printing towards biomedical applications

Therapeutic factors and biomaterial-based delivery tools for degenerative intervertebral disc repair.

Intervertebral disc degeneration (IDD) is the main cause of low back pain (LBP), which significantly impacts global wellbeing and contributes to global productivity declines. Conventional treatment approaches, encompassing conservative and surgical interventions, merely serve to postpone the advancement of IDD without offering a fundamental reversal. Consequently, there is an urgent demand for an effective approach to prevent the progression of IDD. Recent investigations focusing on the treatment of IDD utilizing diverse bioactive substances integrated within various biomaterials have exhibited promising outcomes. Various bioactive substances, encompassing conventional small molecule drugs, small molecule nucleic acids, and cell therapies, exhibit distinct capacities for repairing IDD. Additionally, various biological material delivery systems, such as nano micelles, microspheres, and hydrogels, possess diverse biological and release characteristics. Consequently, these diverse materials and drugs hold promise for advancing the treatment of IDD. This article aims to provide a concise overview of the IDD process and investigate the research advancements in biomaterials and bioactive substances for IDD treatment, delving into their mechanisms.

Use of OneNote class notebook as a combined electronic laboratory notebook and content delivery tool in an introductory biochemistry laboratory course.

The COVID-19 pandemic has forced a shift in thinking regarding the safe delivery of wet laboratory courses. While we were fortunate to have the capacity to continue delivering wet laboratory experiments with physical distancing and other measures in place, modifications to the mechanisms of delivery within courses were necessary to minimize risk to students and teaching staff. One such modification was introduced in BCH370H, an introductory biochemistry laboratory course, where a OneNote Class Notebook (ONCN) was used as an electronic laboratory notebook (ELN) in place of the traditional hardbound paper laboratory notebook (PLN) used prior to the pandemic. The initial reasoning for switching to an ELN was around safety-allowing course staff and students to maintain physical distancing whenever possible and eliminating the need for teaching assistants to handle student notebooks; however, the benefits of the ONCN proved to be significantly more. OneNote acted not only as a place for students to record notes but the Class Notebook's unique features allowed easy integration of other important aspects of the course, including delivery of laboratory manuals, posting of student results, notetaking feedback, sharing of instructional materials with teaching assistants, and more. Student and teacher experiences with the ONCN as used within a fully in person biochemistry laboratory course, as well as learned best practices, are reviewed.

Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off-the-shelf versatile tumor delivery vehicle.

Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells(MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.

Balloon dilation for the treatment of male urethral strictures: a systematic review and meta-analysis

ObjectiveThe use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the...

Transforming native exosomes to engineered drug vehicles: A smart solution to modern cancer theranostics.

Exosomes have been the hidden treasure of the cell in terms of cellular interactions, transportation and therapy. The native exosomes (NEx) secreted by the parent cells hold promising aspects in cancer diagnosis and therapy. NEx has low immunogenicity, high biocompatibility, low toxicity and high stability which enables them to be an ideal prognostic biomarker in cancer diagnosis. However, due to heterogeneity, NEx lacks specificity and accuracy to be used as therapeutic drug delivery vehicle in cancer therapy. Transforming these NEx with their innate structure and multiple receptors to engineered exosomes (EEx) can provide better opportunities in the field of cancer theranostics. The surface of the NEx exhibits numeric receptors which can be modified to pave the direction of its therapeutic drug delivery in cancer therapy. Through surface membrane, EEx can be modified with increased drug loading potentiality and higher target specificity to act as a therapeutic nanocarrier for drug delivery. This review provides insights into promising aspects of NEx as a prognostic biomarker and drug delivery tool along with its need for the transformation to EEx in cancer theranostics. We have also highlighted different methods associated with NEx transformations, their nano-bio interaction with recipient cells and major challenges of EEx for clinical application in cancer theranostics.

Virus-Like Particles as a CRISPR-Cas9 Delivery Tool

CRISPR-Cas9 has been explored as a genome editing tool for various conditions, including cancer and genetic diseases. By examining current research studies, clinical trials, and other literature reviews, here we discuss virus-like particles (VLPs) and their effective delivery of the molecular editing components, CRISPR-Cas9, to various target cell types. In this review, we first provide an overview of CRISPR-Cas9, including key clinical studies where this gene editing tool has proven to be successful, followed by an overview of VLPs, discussing both advantages and limitations. Finally, we highlight key preliminary studies where VLPs have been used specifically as gene editing delivery tools, and discuss how coupling these technologies will continue to positively influence the future of CRISPR-Cas9 genome editing in humans.

Co-development and testing of an extended community pharmacy model of service delivery for managing osteoarthritis: protocol for a sequential, multi-methods study (PharmOA)

BackgroundOsteoarthritis is a common, painful and disabling long-term condition. Delivery of high-quality guideline-informed osteoarthritis care that successfully promotes and maintains supported self-management is imperative. However, osteoarthritis care remains inconsistent, including under use of core non-pharmacological approaches of education, exercise and weight loss.Community pharmacies are an accessible healthcare provider. United Kingdom government initiatives are promoting their involvement in a range of long-term conditions, including musculoskeletal conditions. It is not known what an enhanced community pharmacy role for osteoarthritis care should include, what support is needed to deliver such a role, and whether it would be feasible and acceptable to community pharmacy teams. In this (PharmOA) study, we aim to address these gaps, and co-design and test an evidence-based extended community pharmacy model of service delivery for managing osteoarthritis.MethodsInformed by the Theoretical Domains Framework, Normalisation Process Theory, and the Medical Research Council (MRC) framework for developing complex interventions, we will undertake a multi-methods study involving five phases:1. Systematic review to summarise currently available evidence on community pharmacy roles in supporting adults with osteoarthritis and other chronic (non-cancer) pain.2. Cross-sectional surveys and one-to-one qualitative interviews with patients, healthcare professionals and pharmacy staff to explore experiences of current, and potential extended community pharmacy roles, in delivering osteoarthritis care.3. Stakeholder co-design to: a) agree on the extended role of community pharmacies in osteoarthritis care; b) develop a model of osteoarthritis care within which the extended roles could be delivered (PharmOA model of service delivery); and c) refine existing tools to support community pharmacies to deliver extended osteoarthritis care roles (PharmOA tools).4. Feasibility study to explore the acceptability and feasibility of the PharmOA model of service delivery and PharmOA tools to community pharmacy teams.5. Final stakeholder workshop to: a) finalise the PharmOA model of service delivery and PharmOA tools, and b) if applicable, prioritise recommendations for its wider future implementation.DiscussionThis novel study paves the way to improving access to and availability of high-quality guideline-informed, consistent care for people with osteoarthritis from within community pharmacies.