Tyrosine kinase inhibitors (TKIs) represent a promising category of therapeutic agents for managing edema and neovascular eye diseases (NEDs) such as corneal neovascularization, proliferative diabetic retinopathy and neovascular age-related macular degeneration. By impeding the phosphorylation of receptor tyrosine kinases, TKIs prevent the activation of angiogenic signaling pathways that are vital for cell growth and proliferation. However, the TKIs delivery in ophthalmology presents significant challenges such as toxicity and poor bioavailability. This review discusses emerging TKIs for NEDs, their physicochemical properties, and delivery systems, highlighting strategies such as sustained-release ocular implants, hydrogels, particulate and composite systems. Amid each category, we explore groundbreaking research approaches with a focus on preclinical and clinical studies, providing an in-depth look at the latest advancements in TKI-based delivery systems. Numerous TKI formulations currently under investigation (AXPAXLI, DURAVYU, CLS-AX and D-4517.2) hold the potential to improve therapeutic outcomes and enhance patient adherence, transforming the treatment landscape of NEDs. Advanced TKI delivery platforms, integrated with artificial intelligence-driven tools and minimally invasive technologies may enable more effective and personalized treatment options in the field of eye care.
Curcumin is the main curcuminoid present in turmeric (Curcuma longa). Various studies have shown that curcumin has excellent antimicrobial properties and enhances the wound healing process. Herein, this study we have made an attempt to synthesis and to explore the antibacterial efficacy of two different materials: curcumin reduced graphene oxide (C-rGO) and nano curcumin reduced graphene oxide composite (NC-rGO). These materials were further characterized, and their antibacterial potency was checked against Escherichia coli. According to microstructural characterization the C-rGO composite had a sheet-like uneven structure, whereas NC-rGO composite had spherical morphology. The presence of O-H group in both the composites was confirmed by Fourier transform infrared analysis. The zone of inhibition of C-rGO was 9.5 ± 0.47 mm whereas the zone of inhibition of NC-rGO was 11 ± 0.6 mm. These results indicate that NC-rGO might be used as an antibacterial agent in ointments and dressing bandages to prevent any secondary infection.
Transdermal drug delivery offers several benefits compared with oral delivery, including the bypassing of first-pass metabolism, the ability to target active ingredients for localized effects, and improved patient compliance. Nevertheless, achieving transdermal delivery requires addressing the challenges of permeation through the skin barrier at various levels, including the skin surface, epidermis, dermis, and hypodermis. Nanostructured lipid carriers (NLCs) were invented in the early 1990s as a second generation of lipidic nano carriers. The NLCs are favored over SLNs because they offer greater stability, allowing for higher drug loading, maintaining a consistent drug release profile over time, and preventing gelation during storage. This article aims to offer brief summary of nano system, including the various types of NLCs, their composition, production methods, physiochemical evaluation techniques, mechanistic pathways, recent advancements in transdermal applications, and the use of these carriers for both local and systemic effects. Additionally, it will cover updates on patents and the scalability of NLCs in industrial settings. We also examine important factors for standardization, significant scale-up challenges, and the future prospective of NLCs. Over the past 10 years, the extensive work on NLCs is evident in numerous research reports, consisting patents related to their development, providing a deeper understanding of this growing area of innovation. NLCs serve as an excellent "safe" nano-carrier because of their biodegradable nature and hold significant potential to address the challenges associated with transdermal delivery.
Synthetic ODNs (oligodeoxynucleotides) with immunostimulatory CpG (cytosine-phosphate-guanine) motifs induce an immune-mediated response, activating B cells, T cells, natural killer cells, and competent antigen-presenting cells (APCs). This activation stimulates T helper 1 (TH1) cell activity and induces the release of pro-inflammatory cytokines, making CpG ODNs effective as immunoprotectants, vaccination adjuvants, and antiallergens. The findings that toll-like receptors (TLRs) integrating both adaptive and innate immunity prompted greater interest in TLRs' immunostimulatory capabilities, activators, and effects. Potent adjuvants such as TLR agonists are crucial for effective vaccine formulations because they stimulate dendritic cells (DCs) to activate specific T-cells. Non-methylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) have proven to be successful adjuvants central to TLR9 receptor activation, facilitating the necessary innate immune signaling cascade. Artificially synthesized CpG ODNs are durable, cost-effective, and easy to produce, making them promising candidates for advanced studies on innate immunity and immunoprotection mechanisms. This review discusses CpG ODN-mediated immunomodulatory interventions, their potential as biomedical tools for specific diseases, recent advances in their applications, and related clinical trials from the past decade.
Lipid nanoparticles (LNPs) have emerged as an indispensable tool in biomedical applications due to their versatility, biocompatibility, and capacity to enhance various agents' delivery and therapeutic efficacy. Their expanding role in drug and gene delivery, vaccine development, and diagnostics underscores their significance in advancing modern medical treatments and personalized healthcare. The ability to engineer LNPs to meet specific therapeutic requirements highlights their critical importance in contemporary medicine, providing innovative solutions for treating and diagnosing diverse diseases. The ongoing advancement of liposomal preparation methods is essential for addressing the limitations of traditional approaches and realizing the full therapeutic potential of LNPs. These advancements are poised to yield more efficient, scalable, and customizable liposomal formulations, facilitating the development of next-generation therapies that are safer, more effective, and more accessible. This article provides a detailed analysis of the progress in lipid-based nanotechnology preparation methods, and it examines the fundamental properties and classification of LNPs, their historical context, and the evolution of liposome research. Additionally, it explores various liposome preparation methods, including conventional techniques such as thin-film hydration and emerging novel approaches. Overall, this manuscript offers a comprehensive overview of the pivotal role that advancements in lipid-based nanotechnology preparation methods play in therapeutic innovation.
Exosomes, a type of extracellular vesicle (EV), have received much attention in recent years for their potential in drug delivery systems and therapeutic applications. These nano-sized vesicles, secreted by various plant and animal species, serve as natural carriers of bioactive compounds, including proteins, lipids, and RNA, facilitating intercellular communication between tissue and cells and influencing physiological processes. Stahl and group discovered exosomes from maturing mammalian reticulocytes (immature red blood cells) in 1983, followed by Johnstone and colleagues in 1987, who named them exosomes. Animal-derived exosomes are a popular choice for small-molecule drug delivery due to their biocompatibility and homing properties in various domains, including biology and medicine. After animal-derived exosomes, researchers focused on plant-based exosomes and found several good sources of exosomes from different fruits, vegetables, leaves, and other parts of plants that have different effects like anticancer, anti-inflammatory, antioxidants, and so on. Plant-derived exosomes are also used as carriers for different drugs to treat disease. This review examines the biological component, biogenesis of plant exosomes, their sources, and the methodologies employed for their isolation and purification. We also explore the evaluation techniques for characterizing their biological components, such as proteins and lipids. Furthermore, we discuss the applications of plant-derived exosomes in drug delivery, highlighting their application in different disorders with some research references, including biocompatibility, stability, and targeted delivery. Additionally, this review also addresses the challenges associated with plant-based exosomes in different stages of research including isolation and purification, standardization, optimization, drug loading, and so on. The goal of this in-depth review is to provide insight into the current status of research on exosomes derived from plants and the ways that they could advance in drug delivery systems.
The HIV-1 reservoir is a residual pool of integrated viral genomes that endure in a condition of reversible non-productive infection, notwithstanding suppressive antiretroviral therapy's ability to successfully inhibit HIV-1 replication and evolution. Individual T cells are capable of developing a latent infection due to HIV-1. Even in patients receiving highly effective marketed antiretroviral medication, latent virus survives perpetually in memory T cells and exhibit atypical cellular signaling and metabolic dysfunction, which can cause minor to severe cellular and systemic comorbidities. These include lymphocytic, cardiac, renal, hepatic, and pulmonary dysfunctions as well as genomic DNA damage, telomere attrition, and mitochondrial dysfunction. This latent reservoir is understood to be a substantial challenge for treating HIV-1 infection. The presence of a latent reservoir for HIV-1 can be used to explain the extremely low levels of viremia in patients undergoing antiretroviral therapy. In an effort to eradicate the latent reservoir, several methods are being investigated for reactivating dormant viruses. This review concentrates on figuring out how to awaken latent HIV-1 by adding detailed information about drugs and formulations discovered for latent HIV. This work may provoke the thoughts related for discovering many more promising drugs, and targeting strategies to totally eradicate the HIV.
Microneedle-based delivery systems have emerged as a groundbreaking technology in the realm of targeted cancer therapy. By facilitating the transdermal administration of therapeutic agents, microneedles offer a minimally invasive method to overcome the limitations posed by conventional drug delivery systems. This review comprehensively examines the potential of microneedles to enhance drug bioavailability, improve therapeutic outcomes, and reduce systemic toxicity. We explore the diverse applications of MNs in cancer treatment, including their use in chemotherapy, where MNs enable direct delivery of chemotherapeutic agents to tumor sites, thus maximizing drug efficacy and minimizing adverse effects. Additionally, we discuss the role of MNs in immunotherapy, highlighting how they can be used to deliver immune-modulating agents that activate localized immune responses against cancer cells. Furthermore, the potential of microneedles in gene therapy is addressed, emphasizing their ability to deliver genetic material directly to tumor cells, thereby offering a novel approach to cancer treatment. The review also delves into the challenges associated with MN-based therapies, such as ensuring consistent and controlled drug delivery, addressing patient variability, and overcoming manufacturing and scalability issues. Despite these challenges, the advancements in microneedle technology and the promising results from preclinical and clinical studies underscore their transformative potential in cancer therapy. We emphasize the need for further research and clinical trials to validate the efficacy and safety of microneedles.
The emergence of messenger ribonucleic acid (mRNA) vaccines as an alternative platform to traditional vaccines has been accompanied by advances in nanobiotechnology, which have improved the stability and delivery of these vaccines through novel nanoparticles (NPs). Specifically, the development of NPs for mRNA delivery has facilitated the loading, protection and release of mRNA in the biological microenvironment, leading to the stimulation of mRNA translation for effective intervention strategies. Intriguingly, two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have been permitted for emergency usage authorization to prevent COVID-19 infection by USFDA. Both mRNA vaccines utilized lipidic NPs (LNPs) as a delivery platform and demonstrated superior efficacy and safety profiles compared to traditional vaccines. This review article gives insight into ongoing pre-clinical and clinical developments of mRNA vaccine candidates, their efficacy against coronavirus variants, and analysis of NP-based approaches to recognize their potential for forthcoming growth. This review article highlights recent advances in delivery strategies, including LNPs, polymeric NPs, and exosomes, for effective immunization against COVID-19. The key challenges associated with mRNA NPs have been identified, and potential strategies to overcome these difficulties have been proposed. Production of nanomaterials for specific mRNA applications can offer new insights into next-generation nanomaterials, revolutionizing mRNA technology.
Treating neurological disorders is challenging due to the blood-brain barrier (BBB), which limits therapeutic agents, including proteins and peptides, from entering the central nervous system. Despite their potential, the BBB's selective permeability is a significant obstacle. This review explores recent advancements in protein therapeutics for BBB-targeted delivery and highlights computational tools. Strategies such as nanoparticulate-mediated delivery, nose-to-brain delivery, lipid-based approaches, exosomes, cell-penetrating peptides (CPPs), and BBB shuttle peptides have been developed to overcome this barrier. Nanoparticulate systems deliver protein therapeutics across the BBB and can be surface-functionalized to target therapeutic agents into the brain parenchyma. Nose-to-brain delivery is a minimally invasive approach to bypass the BBB. Lipid-based strategies like liposomal systems and nanostructured lipid carriers enhance protein therapies by overcoming BBB restrictions. Exosomes, with unique lipid and surface protein compositions, and CPPs provide versatile drug delivery across the BBB. BBB shuttle peptides, designed for targeted brain delivery, show enhanced stability, efficiency, and cargo transport. Computational tools, notably molecular dynamics simulations, are essential in optimizing protein therapeutics for BBB penetration. These tools offer insights into molecular interactions, guiding the design and optimization of protein therapeutics for better brain penetration. Despite accuracy, limitations due to the BBB's complexity, integrating realistic models and experimental data can improve predictions.
