Nanotechnology-based Delivery Systems Research Articles

Cationic Carbosilane Dendrimers for Apmnkq2 Aptamer Transfection in Breast Cancer: An Alternative to Traditional Transfectants.

Transfection efficiency is a critical parameter in gene therapy and molecular biology, representing the success rate at which nucleic acids are introduced and expressed in target cells. The combination of aptamers with nanotechnology-based delivery systems has demonstrated remarkable improvements in the transfection efficiency of therapeutic agents and holds significant potential for advancing gene therapy and the development of targeted treatments for various diseases, including cancer. In this work, cationic carbosilane dendritic systems are presented as an alternative to commercial transfection agents, demonstrating an increase in transfection efficiency when used for the internalization of apMNKQ2, an aptamer selected against a target in cancer. Their potential therapeutic use has been evaluated in breast cancer cell lines, MDA-MB-468 and MDA-MB-231, studying the cytotoxicity of the nanoconjugate, the internalization process, and its effect on cellular migration processes.

Advancements in Nanotechnology-Based Paclitaxel Delivery Systems: Systematic Review on Overcoming Solubility, Toxicity, and Drug Resistance Challenges in Cancer Therapy

Background: Paclitaxel (PTX) is a potent chemotherapeutic widely used to treat cancers, including breast and ovarian cancer. However, its poor water solubility, severe side effects, and susceptibility to multidrug resistance (MDR) limit its clinical effectiveness. Recent research focuses on nanotechnology-based delivery systems, such as nanoparticles, liposomes, and dendrimers, to enhance PTX solubility, bioavailability, and targeted delivery. This systematic review analyzed studies from 2019 to 2023 that explore advancements in PTX delivery, focusing on improving therapeutic outcomes and reducing toxicity. Methods: A systematic search was conducted using PubMed, Scopus, Google Scholar, and Web of Science. Forty-five primary research studies meeting inclusion criteria for nanotechnology-based systems, targeted delivery, and MDR strategies were analyzed for improvements in PTX delivery efficacy. Results: The review identified significant advancements in PTX delivery through nanoparticle and targeted systems. Polymer-based nanoparticles, ligand-conjugated carriers, and co-delivery systems with MDR inhibitors showed improved PTX solubility, stability, and selective targeting. Theragnostic platforms combining diagnostics and therapy offered real-time tracking, enhancing personalized treatment. Conclusion: While nanotechnology-based PTX delivery shows promise in overcoming PTX's limitations, challenges remain, particularly in nanoparticle stability, tumor microenvironment barriers, and regulatory hurdles. Future research should address these challenges to enable the clinical translation of PTX systems, providing more effective, accessible cancer treatments worldwide.

Vincristine in Cancer Therapy: Mechanisms, Efficacy, and Future Perspectives.

Cancer remains one of the predominant causes of mortality globally, accounting for over 10 million deaths each year. Despite advancements in medical treatments, the challenge of resistance and treatment failure persists, necessitating innovative approaches. Traditional cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical therapy. In recent years, significant attention has been directed towards plant-derived compounds as potential chemotherapeutic agents and preventive measures against cancer. Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds, vincristine disrupts the cell cycle by causing aberrations in microtubule function, thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine as a potent agent against various malignancies. Its role in combination therapy is crucial, as it is often administered in low doses alongside other chemotherapeutic agents to enhance its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding vincristine's molecular mechanism is paramount. Detailed investigations into its interaction with cellular components can provide insights into its antineoplastic properties. This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship, and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover, it discusses innovative strategies, including nanotechnology-based delivery systems, designed to optimize vincristine formulations. These advanced delivery systems aim to improve bioavailability, target specificity, and minimize systemic toxicity. This comprehensive analysis underscores the critical role of vincristine in contemporary cancer treatment and highlights future directions for research and development in this field.

Enhancing therapy with nano-based delivery systems: exploring the bioactive properties and effects of apigenin.

Apigenin, a potent natural flavonoid, has emerged as a key therapeutic agent due to its multifaceted medicinal properties in combating various diseases. However, apigenin's clinical utility is greatly limited by its poor water solubility, low bioavailability and stability issues. To address these challenges, this review paper explores the innovative field of nanotechnology-based delivery systems, which have shown significant promise in improving the delivery and effectiveness of apigenin. This paper also explores the synergistic potential of co-delivering apigenin with conventional therapeutic agents. Despite the advantageous properties of these nanoformulations, critical challenges such as scalable production, regulatory approvals and comprehensive long-term safety assessments remain key hurdles in their clinical adoption which must be addressed for commercialization of apigenin-based formulations.

Oxidative Stress and Cataract Formation: Evaluating the Efficacy of Antioxidant Therapies.

This comprehensive review investigates the pivotal role of reactive oxygen species (ROS) in cataract formation and evaluates the potential of antioxidant therapies in mitigating this ocular condition. By elucidating the mechanisms of oxidative stress, the article examines how ROS contribute to the deterioration of lens proteins and lipids, leading to the characteristic aggregation, cross-linking, and light scattering observed in cataracts. The review provides a thorough assessment of various antioxidant strategies aimed at preventing and managing cataracts, such as dietary antioxidants (i.e., vitamins C and E, lutein, and zeaxanthin), as well as pharmacological agents with antioxidative properties. Furthermore, the article explores innovative therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, designed to bolster antioxidant defenses in ocular tissues. Concluding with a critical analysis of current research, the review offers evidence-based recommendations for optimizing antioxidant therapies. The current literature on the use of antioxidant therapies to prevent cataract formation is sparse. There is a lack of evidence-based conclusions; further clinical studies are needed to endorse the use of antioxidant strategies in patients to prevent cataractogenesis. However, personalized treatment plans considering individual patient factors and disease stages can be applied. This article serves as a valuable resource, providing insights into the potential of antioxidants to alleviate the burden of cataracts.

The Role of Reactive Oxygen Species in Age-Related Macular Degeneration: A Comprehensive Review of Antioxidant Therapies.

This review article delves into the intricate roles of reactive oxygen species (ROS) in the pathogenesis of age-related macular degeneration (AMD). It presents a detailed analysis of the oxidative stress mechanisms that contribute to the development and progression of these diseases. The review systematically explores the dual nature of ROS in ocular physiology and pathology, underscoring their essential roles in cellular signaling and detrimental effects when in excess. In the context of AMD, the focus is on the oxidative impairment in the retinal pigment epithelium and Bruch's membrane, culminating in the deterioration of macular health. Central to this review is the evaluation of various antioxidant strategies in the prevention and management of AMD. It encompasses a wide spectrum of antioxidants, ranging from dietary nutrients like vitamins C and E, lutein, and zeaxanthin to pharmacological agents with antioxidative properties. The review also addresses novel therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, aiming to enhance antioxidant defense mechanisms in ocular tissues. The article concludes by synthesizing current research findings, clinical trial data, and meta-analyses to provide evidence-based recommendations. It underscores the need for further research to optimize antioxidant therapies, considering individual patient factors and disease stages. This comprehensive review thus serves as a valuable resource for clinicians, researchers, and healthcare professionals in ophthalmology, offering insights into the potential of antioxidants in mitigating the burden of AMD.

The Anticancer Application of Delivery Systems for Honokiol and Magnolol.

Cancer is a leading cause of death worldwide, and the effectiveness of treatment is consistently not at a satisfactory level. This review thoroughly examines the present knowledge and perspectives of honokiol (HON) in cancer therapeutics. The paper synthesizes critical insights into the molecular mechanisms underlying the observed anticancer effects, emphasizing both in vitro and in vivo studies. The effects of HON application, primarily in the common types of cancers, are presented. Because the therapeutic potential of HON may be limited by its physicochemical properties, appropriate delivery systems are sought to overcome this problem. This review discusses the effect of different nanotechnology-based delivery systems on the efficiency of HON. The data presented show that HON exhibits anticancer effects and can be successfully administered to the site of action. Honokiol exerts its anticancer activity through several mechanisms. Moreover, some authors used the combinations of classical anticancer drugs with HON. Such an approach is very interesting and worth further investigation. Understanding HON's multiple molecular mechanisms would provide valuable insights into how HON might be developed as an effective therapeutic. Therefore, further research is needed to explore its specific applications and optimize its efficacy in diverse cancer types.

In vitro investigation of anti-inflammatory activity of propolis/saffron extract/curcumin-loaded ZIF8 nanoparticles and their potential application for treating osteoarthritis

Abstract Background Osteoarthritis (OA) poses a significant healthcare challenge globally, necessitating the development of effective therapeutic interventions. It is crucial to develop novel drug delivery systems for OA treatment. Aims This study explores the potential of propolis, saffron extract, and curcumin-loaded zeolitic imidazolate framework-8 (ZIF8) nanoparticles as a treatment modality for OA. The anti-inflammatory and chondroprotective properties of these natural compounds make them promising candidates for OA management. Methods Through comprehensive in vitro investigations, including scanning electron microscopy (SEM), MTT assays, antiinflammatory assays, cell migration assays, Fourier transform infrared (FTIR) spectroscopy, and release assays, we evaluated the physicochemical and biological characteristics of propolis, saffron extract, and curcumin-loaded ZIF8 nanocarriers. Results Our findings demonstrate that these nanocarriers effectively encapsulated the bioactive compounds, exhibited sustained release profiles, and displayed significant anti-inflammatory properties. Notably, propolis-loaded ZIF8 nanocarriers exhibited superior anti-inflammatory activity compared to other formulations. The encapsulation of propolis, saffron extract, and curcumin within ZIF8 nanoparticles holds promise for enhancing their therapeutic efficacy and ensuring targeted delivery to affected joints in OA treatment. Conclusion This study highlights the potential of nanotechnology-based delivery systems in harnessing the therapeutic benefits of natural compounds for OA management.

CNS Delivery Systems Based on Nanotechnology with Particular Attention to Parkinson's and Alzheimer's Disease –A Review

Abstract:: Nanotechnology has emerged as a promising frontier in the field of drug delivery, offering unprecedented opportunities for precise and targeted interventions in neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. This review explores recent advancements in nanotechnology-based delivery systems designed to enhance drug transport across the blood-brain barrier and facilitate targeted drug delivery to the central nervous system. The unique challenges posed by the intricate central nervous system architecture, particularly in the context of Parkinson's and Alzheimer's diseases, necessitate innovative solutions to improve therapeutic outcomes. The review comprehensively discusses various nanocarrier platforms, including liposomes, polymeric nanoparticles, dendrimers, and exosomes, and their potential applications in drug delivery to the central nervous system (CNS). Special emphasis is placed on addressing the multifaceted challenges associated with neurodegenerative diseases, such as the need for sustained drug release, protection of therapeutic agents from enzymatic degradation, and the efficient crossing of the blood-brain barrier. Furthermore, the review highlights recent breakthroughs in nanotechnology-driven diagnostic and therapeutic approaches, ranging from early detection of disease biomarkers to the targeted delivery of neuroprotective agents. The potential of personalized medicine and the integration of advanced imaging techniques with nanotechnology for precise disease monitoring are also discussed. In conclusion, this review provides a comprehensive overview of recent advancements in nanotechnologybased delivery systems tailored for CNS targeting, with a specific focus on Parkinson's and Alzheimer's diseases. The synthesis of current research findings underscores the transformative potential of nanotechnology in reshaping the landscape of therapeutic strategies for neurodegenerative disorders, offering hope for improved patient outcomes and the development of novel treatment modalities.

Nanoparticle-Mediated Delivery of Viperin: Advancing Therapy Across Diverse Viral Infections

Nanotechnology-based delivery systems hold immense potential to revolutionize antiviral therapy by providing efficient mechanisms of gene delivery systems. Nanoparticles, with their specific characteristics and various properties, offer intriguing potential for improving the efficacy and specificity of antiviral therapies. Viral infection in a host cell triggers a range of host immune responses to prevent viral invasion through the activity of different antiviral proteins. Among these proteins, viperin plays a crucial role in the host's innate immune response against a broad range of viral diseases. Despite its promise, challenges with the delivery and expression of viperin in host cells, restrict its therapeutic application. This review investigates nanoparticle-based gene delivery systems as a potential approach for enhancing viperin activity. Nanoparticles offer a diverse platform for the targeted delivery of therapeutic genes such as viperin, improving efficacy while reducing off-target consequences. Viperin's encapsulation within nanoparticles protects it from degradation, resulting in efficient delivery to target cells and stimulating its antiviral activity. This highlights the latest advances in applications of nanoparticle design and engineering strategies for viperin delivery, including as lipid-based nanoparticles, polymeric nanoparticles, chitosan and carbon-based nanoparticles. These nanocarriers offer precise control over viperin distribution, release dynamics, and cellular absorption, enhancing viperin's therapeutic potential against viral infections. So, the current approach can use a nanoparticle-based gene delivery system to improve antiviral therapies by employing viperin's diverse properties in dealing with a wide variety of viral diseases.

Progress in cancer research on the regulator of phagocytosis CD47, which determines the fate of tumor cells (Review).

Cluster of differentiation 47 (CD47) is a transmembrane protein that is widely and moderately expressed on the surface of various cells and can have an essential role in mediating cell proliferation, migration, phagocytosis, apoptosis, immune homeostasis and other related responses by binding to its ligands, integrins, thrombospondin-1 and signal regulatory protein α. The poor prognosis of cancer patients is closely associated with high expression of CD47 in glioblastoma, ovarian cancer, breast cancer, bladder cancer, colon cancer and hepatocellular carcinoma. Upregulation of CD47 expression facilitates the growth of numerous types of tumor cells, while downregulation of its expression promotes phagocytosis of tumor cells by macrophages, thereby limiting tumor growth. In addition, blocking CD47 activates the cyclic GMP-AMP (cGAMP) synthase/cGAMP/interferon gene stimulating factor signaling pathway and initiates an adaptive immune response that kills tumor cells. The present review describes the structure, function and interactions of CD47 with its ligands, as well as its regulation of phagocytosis and tumor cell fate. It summarizes the therapeutics, mechanisms of action, research advances and challenges of targeting CD47. In addition, this paper provides an overview of the latest therapeutic options for targeting CD47, such as chimeric antigen receptor (CAR) T-cells, CAR macrophages and nanotechnology-based delivery systems, which are essential for future clinical research on targeting CD47.

Nanotechnology-based delivery systems to overcome drug resistance in cancer.

Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics. Multidrug resistance (MDR) in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure. There have been successes in the development of cancer nanomedicine to overcome MDR; however, relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer. This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells. Here, we discuss the advances, types of nanomedicines, and the challenges regarding the translation of invitro to invivo results and their relevance to effective therapies.

Nanoparticle technology for mRNA: Delivery strategy, clinical application and developmental landscape.

The mRNA vaccine, a groundbreaking advancement in the field of immunology, has garnered international recognition by being awarded the prestigious Nobel Prize, which has emerged as a promising prophylactic and therapeutic modality for various diseases, especially in cancer, rare disease, and infectious disease such as COVID-19, wherein successful mRNA treatment can be achieved by improving the stability of mRNA and introducing a safe and effective delivery system. Nanotechnology-based delivery systems, such as lipid nanoparticles, lipoplexes, polyplexes, lipid-polymer hybrid nanoparticles and others, have attracted great interest and have been explored for mRNA delivery. Nanoscale platforms can protect mRNA from extracellular degradation while promoting endosome escape after endocytosis, hence improving the efficacy. This review provides an overview of diverse nanoplatforms utilized for mRNA delivery in preclinical and clinical stages, including formulation, preparation process, transfection efficiency, and administration route. Furthermore, the market situation and prospects of mRNA vaccines are discussed here.

Nanoformulations of curcumin: An alliance for effective cancer therapeutics

Cancer is intimidating in its diversity, genetics, epigenetics, pathology, diagnosis, and response to therapy. The high rate of recurrence and development of resistance to therapies hinder the prognosis and the inadvertent side effects of contemporary medications can reduce the quality of life in patients. These observations emphasize the need for multi-targeted treatments that are not only relatively safe and economical, but also provide a more effective alternative to the conventional treatment modalities. Over the last few decades, scientific data has demonstrated that curcumin has a wide range of anti-cancer effects that are orchestrated via affecting diverse cancer signaling pathways. Nonetheless, the therapeutic applicability of curcumin is severely limited due to its low water solubility, poor oral absorption, and rapid clearance. These limitations prompted the development of various curcumin formulations including nanotechnology based delivery systems for the prevention and treatment of cancers. Therefore, we aimed to review the potential benefits of nanocurcumin in treating various cancer. We conducted a comprehensive search on the PubMed database to identify relevant publications concerning the use of nanocurcumin in cancer treatment, utilizing the search term 'nanocurcumin and cancer'. This review summarizes various preclinical and clinical studies that highlight the anticancer activities of curcumin nanoformulations including cyclodextrin complexes, dendrimers, exosomes, liposomes, gold nanoparticles (NPs), graphene nanocomposites, magnetic NPs, micelles, nanogels, polymeric NPs and solid-lipid NPs (SLNs). We further presented cellular mechanisms and clinical investigations, thus, emphasizing its potential in cancer prevention and treatment or even as an adjuvant therapy with conventional drugs to enhance therapeutic results in cancer patients.

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, advanced therapy medicinal products (ATMPs) have also been highlighted, with optimistic perspectives for the pediatric population. Despite the results achieved using these innovative therapies, a workforce that congregates pediatric patients and/or caregivers, healthcare stakeholders, drug developers, and physicians continues to be of utmost relevance to promote standardized guidelines for pediatric drug development, enabling a fast lab-to-clinical translation. Therefore, taking into consideration the significance of this topic, this work aims to compile the current landscape of pediatric drug development by (1) outlining the historic regulatory panorama, (2) summarizing the challenges in the development of pediatric drug formulation, and (3) delineating the advantages/disadvantages of using innovative approaches, such as nanomedicines and ATMPs in pediatrics. Moreover, some attention will be given to the role of pharmaceutical technologists and developers in conceiving pediatric medicines.

Application of Nanotechnology in Plant Genetic Engineering.

The ever-increasing food requirement with globally growing population demands advanced agricultural practices to improve grain yield, to gain crop resilience under unpredictable extreme weather, and to reduce production loss caused by insects and pathogens. To fulfill such requests, genome engineering technology has been applied to various plant species. To date, several generations of genome engineering methods have been developed. Among these methods, the new mainstream technology is clustered regularly interspaced short palindromic repeats (CRISPR) with nucleases. One of the most important processes in genome engineering is to deliver gene cassettes into plant cells. Conventionally used systems have several shortcomings, such as being labor- and time-consuming procedures, potential tissue damage, and low transformation efficiency. Taking advantage of nanotechnology, the nanoparticle-mediated gene delivery method presents technical superiority over conventional approaches due to its high efficiency and adaptability in different plant species. In this review, we summarize the evolution of plant biomolecular delivery methods and discussed their characteristics as well as limitations. We focused on the cutting-edge nanotechnology-based delivery system, and reviewed different types of nanoparticles, preparation of nanomaterials, mechanism of nanoparticle transport, and advanced application in plant genome engineering. On the basis of established methods, we concluded that the combination of genome editing, nanoparticle-mediated gene transformation and de novo regeneration technologies can accelerate crop improvement efficiently in the future.

Computational simulation on the study of Tacrolimus and its improved dermal retention using Poly(Ԑ-caprolactone) nanocapsules

Tacrolimus (TAC) is a drug from natural origin that can be used for topical application to control autoimmune skin diseases such as atopic dermatitis, psoriasis, and vitiligo. Computational simulation based on quantum mechanics theory by solving Schrödinger Equation for n-body problem may allow the theoretical calculation of drug geometry, charge distribution and dipole moment, electronic levels and molecular orbitals, electronic transitions, and vibrational transitions. Additionally, the development of novel nanotechnology-based delivery systems containing TAC can be an approach for reducing the dose applied topically, increasing dermal retention, and reducing the reported side effects due to the controlled release pattern. Firstly, this paper was devoted to obtaining the molecular, electronic, and vibrational data for TAC by using five semi-empirical (SE) methods and one Density Functional Theory (DFT) method in order to expand the knowledge about the drug properties by computational simulation. Then, this study was carried out to prepare TAC-loaded poly(ԑ-caprolactone) nanocapsules by interfacial polymer deposition following solvent displacement and investigate the in vitro drug permeation using the Franz diffusion cell and the photoacoustic spectroscopy. Computational simulations were compared in the three schemes SE/SE, SE/DFT, and DFT/DFT, where the first method represented the procedure used for geometry optimization and the second one was performed to extract electronic and vibrational properties. Computational data showed correspondence with TAC geometry description and electronic properties, with few differences in HOMO – LUMO gap (Δ) and dipole values. The SE/DFT and DFT/DFT methods presented a better drug description for the UV–Vis, Infrared, and Raman spectra with low deviation from experimental values. Franz cell model demonstrated that TAC was more delivered across the Strat-M® membrane from the solution than the drug-loaded poly(ԑ-caprolactone) nanocapsules. Photoacoustic spectroscopy assay revealed that these nanocapsules remained more retained into the Strat-M® membranes, which is desirable for the topical application.

Celecoxib-Loaded Cubosomal Nanoparticles as a Therapeutic Approach for Staphylococcus aureus In Vivo Infection.

There is a great need for novel approaches to treating bacterial infections, due to the vast dissemination of resistance among pathogenic bacteria. Staphylococcus aureus are ubiquitous Gram-positive pathogenic bacteria and are rapidly acquiring antibiotic resistance. Here, celecoxib was encapsulated into cubosomal nanoparticles, and the particle morphology, size distribution, zeta potential, entrapment efficiency, and celecoxib release were evaluated in vitro. Also, a systemic infection model in mice elucidated the in vivo antibacterial action of the celecoxib cubosomes. Cubosomes are a nanotechnology-based delivery system which can adhere to the external peptidoglycan layers of Gram-positive bacteria and penetrate them. The size distribution investigation revealed that the prepared celecoxib-loaded cubosomes had a mean particle size of 128.15 ± 3.04 nm with a low polydispersity index of 0.235 ± 0.023. The zeta potential measurement showed that the prepared cubosomes had a negative surface charge of -17.50 ± 0.45, indicating a highly stable nanodispersion formation with little susceptibility to particle aggregation. The cubosomal dispersion exhibited an entrapment efficiency of 88.57 ± 2.36%. The transmission electron micrograph for the prepared celecoxib-loaded cubosomes showed a narrow size distribution for the cubosomal nanoparticles, which had a spherical shape and were non-aggregated. The tested cubosomes diminished the inflammation in the treated mice's liver and spleen tissues, as revealed by hematoxylin and eosin stain and Masson's trichrome stain. The immunostained tissues with nuclear factor kappa B and caspase-3 monoclonal antibodies revealed a marked decrease in these markers in the celecoxib-treated group, as it resulted in negative or weak immunostaining in liver and spleen that ranged from 4.54% to 17.43%. This indicates their inhibitory effect on the inflammatory pathway and apoptosis, respectively. Furthermore, they reduced the bacterial burden in the studied tissues. This is alongside a decrease in the inflammatory markers (interleukin-1 beta, interleukin-6, cyclooxygenase-2, and tumor necrosis factor-alpha) determined by ELISA and qRT-PCR. The IL-1β levels were 16.66 ± 0.5 pg/mg and 17 ± 0.9 pg/mg in liver and spleen, respectively. Also, IL-6 levels were 85 ± 3.2 pg/mg and 84 ± 2.4 pg/mg in liver and spleen, respectively. In conclusion, the current study introduced cubosomes as an approach for the formulation of celecoxib to enhance its in vivo antibacterial action by improving its oral bioavailability.

Revitalizing allicin for cancer therapy: advances in formulation strategies to enhance bioavailability, stability, and clinical efficacy.

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.

Attenuation of epithelial-mesenchymal transition via SGLT2 inhibition and diabetic cataract suppression by dapagliflozin nanoparticles treatment

AimsChronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects. Main methodsSD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6–12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats. Key findingsIn this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution. SignificanceTaken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts.