Revolutionizing Lung Cancer Treatment: Innovative CRISPR-Cas9 Delivery Strategies.

Lung carcinoma, including both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), remains a significant global health challenge due to its high morbidity and mortality rates. The objsective of this review is to meticulously examine the current advancements and strategies in the delivery of CRISPR-Cas9 gene-editing technology for the treatment of lung carcinoma. This technology heralds a new era in molecular biology, offering unprecedented precision in genomic modifications. However, its therapeutic potential is contingent upon the development of effective delivery mechanisms that ensure the efficient and specific transport of gene-editing tools to tumor cells. We explore a variety of delivery approaches, such as viral vectors, lipid-based nanoparticles, and physical methods, highlighting their respective advantages, limitations, and recent breakthroughs. This review also delves into the translational and clinical significance of these strategies, discussing preclinical and clinical studies that investigate the feasibility, efficacy, and safety of CRISPR-Cas9 delivery for lung carcinoma. By scrutinizing the landscape of ongoing clinical trials and offering translational perspectives, we aim to elucidate the current state and future directions of this rapidly evolving field. The review is structured to first introduce the problem and significance of lung carcinoma, followed by an overview of CRISPR-Cas9 technology, a detailed examination of delivery strategies, and an analysis of clinical applications and regulatory considerations. Our discussion concludes with future perspectives and challenges, such as optimizing delivery strategies, enhancing specificity, mitigating immunogenicity concerns, and addressing regulatory issues. This comprehensive overview seeks to provide insights into the potential of CRISPR-Cas9 as a revolutionary approach for targeted therapies and personalized medicine in lung carcinoma, emphasizing the importance of delivery strategy development in realizing the full potential of this groundbreaking technology.

Nucleic acids based integrated macromolecular complexes for SiRNA delivery: Recent advancements.

The therapeutic potential of small interfering RNA (siRNA) is monumental, offering a pathway to silence disease-causing genes with precision. However, the delivery of siRNA to target cells in-vivo remains a formidable challenge, owing to degradation by nucleases, poor cellular uptake and immunogenicity. This overview examines recent advancements in the design and application of nucleic acid-based integrated macromolecular complexes for the efficient delivery of siRNA. We dissect the innovative delivery vectors developed in recent years, including lipid-based nanoparticles, polymeric carriers, dendrimer complexes and hybrid systems that incorporate stimuli-responsive elements for targeted and controlled release. Advancements in bioconjugation techniques, active targeting strategies and nanotechnology-enabled delivery platforms are evaluated for their contribution to enhancing siRNA delivery. It also addresses the complex interplay between delivery system design and biological barriers, highlighting the dynamic progress and remaining hurdles in translating siRNA therapies from bench to bedside. By offering a comprehensive overview of current strategies and emerging technologies, we underscore the future directions and potential impact of siRNA delivery systems in personalized medicine.

Graphene Oxide, a Prominent Nanocarrier to Reduce the Toxicity of Alzheimer's Proteins: A Revolution in Treatment.

Graphene oxide, a derivative of graphene, has recently emerged as a promising nanomaterial in the biomedical field due to its unique properties. Its potential as a nanocarrier in the treatment of Alzheimer's disease represents a significant advancement. This abstract outlines a study focused on utilizing graphene oxide to reduce the toxicity of Alzheimer's proteins, marking a revolutionary approach in treatment strategies. The pathological features of Alzheimer's disease, primarily focusing on the accumulation and toxicity of amyloid-beta proteins, have been described in this review. These proteins are known to form plaques in the brain, leading to neuronal damage and the progression of Alzheimer's disease. The current therapeutic strategies and their limitations are briefly reviewed, highlighting the need for innovative approaches. Graphene oxide, with its high surface area, biocompatibility, and ability to cross the blood-brain barrier, is introduced as a novel nanocarrier. The methodology involves functionalizing graphene oxide sheets with specific ligands that target amyloid-beta proteins. This functionalization facilitates the binding and removal of these toxic proteins from the brain, potentially alleviating the symptoms of Alzheimer's disease. Preliminary findings indicate a significant reduction in amyloid-beta toxicity in neuronal cell cultures treated with graphene oxide nanocarriers. The study also explores the biocompatibility and safety profile of graphene oxide in biological systems, ensuring its suitability for clinical applications. It calls for further research and clinical trials to fully understand and harness the benefits of this nanotechnology, paving the way for a new era in neurodegenerative disease therapy.

Beyond the Maze: Recent Advancements in Molecular and Cellular Tethered Drug Delivery Systems.

The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine.

Guanidinium-based Integrated Peptide Dendrimers: Pioneer Nanocarrier in Cancer Therapy.

The landscape of cancer therapy has witnessed a paradigm shift with the emergence of innovative delivery systems, and Guanidinium-based Peptide Dendrimers have emerged as a vanguard in this transformative journey. With their unique molecular architecture and intrinsic biocompatibility, these dendrimers offer a promising avenue for the targeted delivery of therapeutic cargo in cancer treatment. This comprehensive review delves into the intricate world of Guanidinium- based Peptide Dendrimers, unraveling their structural intricacies, mechanisms of action, and advancements that have propelled them from laboratory curiosities to potential clinical champions. Exploiting the potent properties of guanidinium, these dendrimers exhibit unparalleled precision in encapsulating and transporting diverse cargo molecules, ranging from conventional chemotherapeutics to cutting-edge nucleic acids. The review navigates the depths of their design principles, investigating their prowess in traversing the complex terrain of cellular barriers for optimal cargo delivery. Moreover, it delves into emerging trends, such as personalized therapeutic approaches, multimodal imaging, and bioinformatics-driven design, highlighting their potential to redefine the future of cancer therapy. Crucially, the review addresses the pivotal concerns of biocompatibility and safety, examining cytotoxicity profiles, immune responses, and in vivo studies. It underscores the importance of aligning scientific marvels with the stringent demands of clinical applications. Through each section, the narrative underscores the promises and possibilities that Guanidinium-based Peptide Dendrimers hold and how they can potentially reshape the landscape of precision cancer therapy.

Development of nanoemulgel of 5-Fluorouracil for skin melanoma using glycyrrhizin as a penetration enhancer.

The purpose of this study was to enhance the topical delivery of 5-Fluorouracil (5-FU), a cancer treatment, by developing a nanoemulgel formulation. Glycyrrhizin (GLY), a natural penetration enhancer has been investigated to exhibit synergistic effects with 5-FU in inhibiting melanoma cell proliferation and inducing apoptosis, Hence, GLY, along with suitable lipids was utilized to create an optimized nanoemulsion (NE) based gel. Solubility studies and ternary phase diagram revealed isopropyl myristate (IPM), Span 80, Tween 80 as Smix and Transcutol P as co-surfactant. IPM demonstrates excellent solubilizing properties facilitates higher drug loading, ensuring efficient delivery to the target site.,The optimized formulation consisting of 40 % IPM, 30 % of mixture of Tween80: Span80 (Smix) and 15 % Transcutol P provides with a nanometric size of 64.1 ± 5.13 nm and drug loading of 97.3 ± 5.83 %. The optimized formulation observed with no creaming and breakeing of NE and found thermodynamically stable during different stress conditions (temperatures of 4.0 °C and 45.0 °C) and physical thawing (-21.0 ± 0.50 °C to 20.0 ± 0.50 °C). The NE was then transformed into a nanoemulgel (NEG) using 1.5 % w/w Carbopol base and 0.1 % w/w glycyrrhizin. The ex vivo permeability studies showed significant enhancements in drug permeability with the GLY-based 5-FU-NEG formulation compared to pure 5-FU gel in excised pig skin upto1440 min in PBS 7.4 as receptor media. The IC50 values for Plain 5-FU gel, 5-FU-NEG, and GLY-based 5-FU-NEG were found to be 20 µg/mL, 1.1 µg/mL, and 0.1 µg/mL, respectively in B16F10 cell lines. The percentage intracellular uptake of GLY-5-FU-NEG and 5-FU-NEG was found to be 44.3 % and 53.6 %, respectively. GLY-based 5-FU-NEG formulation showed alterations in cell cycle distribution, in compared to 5-FU-NE gel. The overall findings suggest that the GLY-based 5-FU-NEG holds promise for improving anti-melanoma activity.

A Screening Approach to the Safe-and-Sustainable-by-Design Development of Advanced Insulation Materials.

Herein, a Safe-and-Sustainable-by-Design (SSbD) screening strategy on four different inorganic aerogel mats and two conventional mineral wools for ranking purposes is demonstrated. Given that they do not consist of particles, the release is first simulated, addressing three occupational exposure scenarios, realistic for their intended use as building insulators. No exposure to consumers nor to the environment is foreseen in the use phase, however, aerosols may be released during mat installation, posing an inhalation risk for workers. All four aerogel mats release more respirable dust than the benchmark materials and 60% thereof deposits in the alveolar region according to modelling tools. The collected aerogel dust allows for subsequent screening of hazard implications via two abiotic assays: 1) surface reactivity in human blood serum; 2) biodissolution kinetics in lung simulant fluids. Both aerogels and conventional insulators show similar surface reactivity. Differences in biodissolution are influenced by the specifically designed organic and inorganic structural modifications. Aerogel mats are better-performing insulators (2-fold lower thermal conductivity than the benchmark) However, this work demonstrates how investment decisions can be balanced with safety and sustainability aspects. Concepts of analogy and similarity thus support easily accessible methods to companies for safe and economically viable innovation with advanced materials.

Revolutionizing cellular energy: The convergence of mitochondrial dynamics and delivery technologies.

The intersection of mitochondrial dynamics and delivery technologies heralds a paradigm shift in cellular biology and therapeutic intervention. Mitochondrial dynamics, encompassing fusion, fission, transport, and mitophagy, are critical for cellular energy production, signaling, and homeostasis. Dysregulation of these processes is implicated in a myriad of diseases, including neurodegenerative disorders, cardiovascular diseases, and cancer. Concurrently, advances in delivery technologies, such as nanocarriers, targeted delivery systems, and gene editing tools, offer unprecedented opportunities to manipulate mitochondrial function directly. This review synthesizes current knowledge on mitochondrial dynamics, examines recent breakthroughs in targeted delivery methods, and explores their potential convergence to modulate cellular energetics for therapeutic purposes. By integrating insights from biology, chemistry, and bioengineering, this review highlights the innovative approaches being developed to enhance mitochondrial function, underscoring the potential of this convergence to address complex diseases. This interdisciplinary perspective not only broadens our understanding of cellular processes but also paves the way for novel therapeutic strategies, marking a significant step forward in the quest for precision medicine and targeted interventions in mitochondrial-related diseases.

Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies.

Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.

Organelle Targeted Drug Delivery: Key Challenges, Recent Advancements and Therapeutic Implications.

Organelle-specific targeted drug delivery has emerged as a promising approach in the field of drug delivery and therapeutics. This innovative strategy involves the precise delivery of therapeutic agents to specific organelles within cells, such as the nucleus, mitochondria, endoplasmic reticulum, or lysosomes, with the aim of enhancing drug efficacy while minimizing offtarget effects. Despite its tremendous potential, organelle-specific drug delivery faces several key challenges. One major challenge is the development of delivery systems that can accurately navigate the complex intracellular environment and deliver drugs exclusively to the desired organelles. Achieving this level of precision demands advanced nanotechnology and biomaterials engineering. Furthermore, ensuring the safety and biocompatibility of these delivery systems is paramount. Recent advancements in this field include the development of nanocarriers, such as liposomes, nanoparticles, and dendrimers, designed to target specific organelles through ligandreceptor interactions or pH-responsive mechanisms. Additionally, advancements in molecular biology and genetic engineering have enabled the design of genetically encoded organellespecific drug delivery systems. The therapeutic implications of organelle-specific drug delivery are vast. This approach has the potential to revolutionize the treatment of diseases with organelle- specific pathologies, such as neurodegenerative disorders, cancer, and mitochondrial diseases. By precisely targeting the organelles involved in disease progression, the efficacy of therapies can be significantly improved while minimizing collateral damage to healthy tissues.

Novel Biomaterials Based Strategies for Neurodegeneration: Recent Advancements and Future Prospects.

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, pose significant challenges for effective treatment due to the complex nature of the central nervous system and the limited delivery of therapeutic agents to the brain. Biomaterial-based drug delivery systems offer promising strategies to overcome these challenges and improve therapeutic outcomes. These systems utilize various biomaterials, such as nanoparticles, hydrogels, and implants, to deliver drugs, genes, or cells to the affected regions of the brain. They provide advantages such as targeted delivery, controlled release, and protection of therapeutic agents. This review examines the role of biomaterials in drug delivery for neurodegeneration, discussing different biomaterialbased approaches, including surface modification, encapsulation, and functionalization techniques. Furthermore, it explores the challenges, future perspectives, and potential impact of biomaterialbased drug delivery systems in the field of neurodegenerative diseases.

A Complete Sojourn of Current Trends in Gastro-retentive Drug Delivery System: Recent Advances and Patent Survey.

The current work aims to provide a complete sojourn on gastro-retentive drug delivery system (GRDDS) along with formulation methods, polymer selection, and in vitro/ in vivo challenges with finished dosage forms. Ideally, a biopharmaceutical-hindered drug has a rapid clearance and erratic bioavailability due to its low aqueous solubility and permeability. Additionally, it also suffers from high first-pass metabolism and pre-systemic gut wall clearance. Gastro-retentive drug delivery systems have become an emerging technology where newer methodologies and scientific approaches have been used to provide the controlled release of drugs and provide a protective mechanism in the stomach. By the virtue of utilizing GRDDS as a dosage form, these formulations increase Gastroretention time (GRT) which prolongs the controlled release of the drug in the dosage form. GRDDS contribute to increased drug bioavailability and targeting at a site of action, which enhances therapeutic action and offers significant patient compliance. Furthermore, the present work also highlighted the critical role of polymers in favoring drug retention across GIT with the mechanism of gastro-retention and recommended concentration ranges. The emerging technology is also highlighted by the approved drug products and patented formulations in the recent decade which is depicted in a justified manner. GRDDS formulations have demonstrated clinical efficacy, which is supported by a compilation of patents for cutting-edge innovations in dosage forms that can be held in the stomach for an extended period of time.

A sojourn on mitochondria targeted drug delivery systems for cancer: Strategies, clinical and future prospects.

Mitochondria, often referred to as the powerhouses of the cell, have emerged as promising targets for cancer therapy due to their pivotal roles in cell survival, apoptosis, and energy metabolism. This sojourn emphasizes the significance of mitochondria-targeted drug delivery systems in cancer therapeutics. The unique characteristics of cancer cell mitochondria, such as altered membrane potential and distinct lipid composition, offer an avenue for selective drug targeting. Several strategies have been explored to exploit these features, including the use of lipophilic cations, mitochondria-penetrating peptides, and nanocarriers tailored for mitochondrial delivery. Mitochondria-targeted drug delivery systems have demonstrated enhanced therapeutic efficacy and reduced systemic toxicity in preclinical models. Some of these systems have made a successful transition to clinical trials, illustrating their potential in real-world oncology settings. However, there remain challenges like intracellular barriers, potential off-target effects, and the complexity of tumor heterogeneity that must be addressed to fully harness the potential of mitochondria-targeted drug delivery systems. As research progresses, it is anticipated that innovative approaches and technologies will be developed to improve the specificity and efficacy of mitochondrial targeting, paving the way for more effective and safer cancer treatments in the future. This review serves as a comprehensive guide to the current state of mitochondria-targeted drug delivery systems for cancer, highlighting key strategies, clinical progress, and prospective avenues for future research.

A Short Appraisal of Magnetic Nanoparticles for Breast Cancer: In vitro and In vivo Research.

The increasing incidence of breast cancer and the associated morbidity due to higher metastasis created the urge to develop a nanocarrier that can be used as a potent therapeutic carrier with targeting efficacy. The use of superparamagnetic nanoparticles in breast cancer research and treatment has gained considerable attention in recent years. Magnetic nanoparticles (MNPs) can be used to construct nanocarriers since they possess superior properties such as superparamagnetism, easy surface functionalization to attach ligands, and non-immunogenic. MNPs are superior carriers that are used to target cancer cells without harming the normal cells in the body, which leads to therapeutic efficacy in the body. Along with their established anticancer potential and enhanced drug concentration at endosomal pH, the superparamagnetic property of MNPs was further exploited for their applications in reticuloendothelial uptake, drug delivery, medical imaging, and theranostics applications in breast cancer. Moreover, the clinical translational of MNPs, along with future prospects and key challenges in vivo, have been duly presented in the final review. The scientists preferred the ongoing research in MNPs due to their high biocompatibility and ease of targeting at molecular and cellular levels. The review highlighted the in vitro and in vivo research and patent supported data for potential use of MNPs for the treatment of breast cancer.

Exploiting nuclear-mitochondrial cross-talk in theranostics: Enhancing drug delivery and diagnostic precision.

The dynamic interplay between nuclear and mitochondrial processes plays a pivotal role in cellular homeostasis and disease progression. Exploiting this nuclear-mitochondrial cross-talk has emerged as a promising avenue in the field of theranostics, offering enhanced drug delivery and diagnostic precision for a wide range of medical conditions, particularly cancer. This abstract provides a brief overview of the key concepts and recent advancements in this rapidly evolving field. Recent research has elucidated the significance of mitochondrial dysfunction in various diseases, including cancer. Mitochondria, often referred to as the "powerhouses" of the cell, not only regulate energy production but also contribute to critical processes such as apoptosis, ROS generation, and metabolic signaling. Dysregulation of these mitochondrial functions is frequently associated with disease pathogenesis. In theranostics, the targeted modulation of mitochondrial function holds great promise. Mitochondria-targeted drug delivery systems have been designed to selectively deliver therapeutic agents to these organelles, thereby mitigating mitochondrial dysfunction while minimizing off-target effects. This precise drug delivery enhances the therapeutic efficacy of anticancer drugs and reduces the risk of drug resistance. Moreover, the diagnostic potential of nuclear-mitochondrial cross-talk is being harnessed to develop novel biomarkers and imaging techniques. Mitochondrial DNA mutations and alterations in mitochondrial metabolism serve as valuable indicators of disease progression and drug responsiveness. Non-invasive imaging modalities, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), have been employed to visualize mitochondrial activity and assess therapeutic outcomes.

Quality-by-Design Approach for Investigating the Efficacy of Tacrolimus and Hyaluronic Acid-Loaded Ethosomal Gel in Dermal Management of Psoriasis: In Vitro, Ex Vivo, and In Vivo Evaluation.

Psoriasis is an auto-immune condition with high keratinocyte hyperproliferation due to lower p53 and p22 levels. Tacrolimus, an immune suppressor, is considered one of the most effective drugs in suppressing psoriasis. Systematic administration of tacrolimus often leads to challenging side effects, namely increased infection risk, renal toxicity, neurological symptoms such as tremors and headaches, gastrointestinal disturbances, hypertension, skin-related problems, etc. To address this, a nanocarrier-based formulation of tacrolimus along with inclusion of hyaluronic acid was developed. The optimization and formulation of ethosomes via the ethanol injection technique were done based on the Box-Behnken experimental design. The results revealed hyaluronic acid-based tacrolimus ethosomes (HA-TAC-ETH) had nanometric vesicle size (315.7 ± 2.2 nm), polydispersity index (PDI) (0.472 ± 0.07), and high entrapment efficiency (88.3 ± 2.52%). The findings of drug release and skin permeation showed sustained drug release with increased dermal flux and enhancement ratio. The effectiveness of HA-TAC-ETH was confirmed in an imiquimod (5%)-prompted psoriasis model. The skin irritation score and Psoriasis Area and Severity Index (PASI) score indicated that HA-TAC-ETH gel has validated a decline in the entire factors (erythema, edema, and thickness) in the imiquimod-induced psoriasis model in contrast with TAC-ETH gel and TAC ointment. The fabricated HA-TAC-ETH opt gel proved to be safe and effective in in vivo studies and could be employed to treat psoriasis further.

A Short Appraisal of Biomimetic Hydrogels to Improve Penetration of Poorly Permeable Drugs.

Effective drug delivery to target sites is critical for achieving desired therapeutic outcomes. However, the poor permeability of certain drugs poses significant challenges in achieving adequate drug concentrations at the desired locations. Biomimetic hydrogels have emerged as a promising approach to enhance the penetration of poorly permeable drugs. These hydrogels, designed to mimic natural biological systems, offer unique properties and functionalities that enable improved drug permeation. In this review, we provide a comprehensive appraisal of the role of biomimetic hydrogels in enhancing drug penetration. We discuss the design principles, properties, and mechanisms by which these hydrogels facilitate drug permeation. Specifically, we explore the applications and benefits of biomimetic hydrogels in controlled drug release, mimicking extracellular matrix microenvironments, promoting cell-mimetic interactions, and enabling targeted drug delivery. Through an examination of key studies and advancements, we highlight the potential of biomimetic hydrogels in enhancing drug penetration and their implications for therapeutic interventions. This review contributes to a deeper understanding of biomimetic hydrogels as a promising strategy for overcoming drug penetration challenges and advancing drug delivery systems, ultimately leading to improved therapeutic efficacy.