Nanoparticle-based Drug Delivery Systems Research Articles

Novel 2-D phosphorene-based drug delivery system for anti-HIV zidovudine drug to enhance the therapeutic effects: A first-principles based study

The development of nanoparticle-based drug delivery systems (DDS) has become a deemed approach to obtain the desired therapeutic effects. Herein, we present 2-dimensional phosphorene-based DDS for the zidovudine (AZT) drug to obtain chemical stability, biodegradability, biocompatibility, and enhanced bioavailability. First-principles-based protocols suggest that AZT prefers to interact with phosphorene via P--H interaction in the gas phase, with an ideal adsorption energy of −0.20 eV (BSSE corrected −0.17 eV) and −2.112 eV (BSSE corrected −1.68 eV). Our results show that the AZT@phosphorene complex manifests excellent solubility in aqueous medium. Effective and robust AZT-drug off-loading is expected at the biochemically active site as indicated by weak van der Waals interaction with the phosphorene carrier. The electron localization function (ELF) and the natural bonding orbital (NBO) analysis were used to investigate the charge transfer mechanism of the complex. The electron density of phosphorene varies significantly following complex formation indicating new molecular orbitals formation and electron transfer with minimal energy. The photoinduced electron transfer analysis explains quenching at randomly selected excited states. Our results imply a significant fluorescence detection procedure which is highly beneficial for the systematic distribution of AZT medicine to the targeted biologically activated site. Overall, our first-principles-based investigation protocols suggest that phosphorene could potentially be employed as an efficient anti-HIV AZT-drug carrier to improve therapeutic effects.

TARGETING ANGIOGENESIS WITH FLUPHENAZINE-ZINC OXIDE NANOCONJUGATES: A POTENTIAL MECHANISM FOR IMPROVING ANTIPSYCHOTIC EFFICACY

Objective: This study aimed to develop a more effective formulation of Fluphenazine (FLP) for the management of psychosis. Antipsychotics are widely used for the treatment of severe mental disorders such as schizophrenia and bipolar disorder. However, their clinical use is limited due to various side effects and low efficacy in a large number of patients. Nanoparticle-based drug delivery systems have shown great potential in improving the pharmacokinetics and pharmacodynamics of various drugs, including antipsychotics. Zinc oxide nanoparticles (ZnO NPs) have emerged as a promising carrier for drug delivery due to their unique physicochemical properties, biocompatibility, and low toxicity. Methods: In this study, we reported the preparation and characterization of FLU-encapsulated ZnO NPs (FLU-ZnO-NPs) for the management of psychosis. The synthesized FLU-ZnO-NPs were characterized using various techniques, such as X-Ray Diffractometer, Energy Dispersive X-Ray analysis, Transmission Electron Microscopy, and Zetasizer (Malvern). Results: The characterization results showed that the synthesized FLU-ZnO-NPs had improved solubility, enhanced bioavailability, targeted delivery, and reduced toxicity. Conclusion: The development of FLU-ZnO-NPs could provide a more effective and safe treatment option for patients with mental disorders.

Exploring the impact of severity in hepatic fibrosis disease on the intrahepatic distribution of novel biodegradable nanoparticles targeted towards different disease biomarkers

Nanoparticle-based drug delivery systems (DDS) have shown promising results in reversing hepatic fibrosis, a common pathological basis of chronic liver diseases (CLDs), in preclinical animal models. However, none of these nanoparticle formulations has transitioned to clinical usage and there are currently no FDA-approved drugs available for liver fibrosis. This highlights the need for a better understanding of the challenges faced by nanoparticles in this complex disease setting. Here, we have systematically studied the impact of targeting strategy, the degree of macrophage infiltration during fibrosis, and the severity of fibrosis, on the liver uptake and intrahepatic distribution of nanocarriers. When tested in mice with advanced liver fibrosis, we demonstrated that the targeting ligand density plays a significant role in determining the uptake and retention of the nanoparticles in the fibrotic liver whilst the type of targeting ligand modulates the trafficking of these nanoparticles into the cell population of interest - activated hepatic stellate cells (aHSCs). Engineering the targeting strategy indeed reduced the uptake of nanoparticles in typical mononuclear phagocyte (MPS) cell populations, but not the infiltrated macrophages. Meanwhile, additional functionalization may be required to enhance the efficacy of DDS in end-stage fibrosis/cirrhosis compared to early stages.

Delivering drugs to tubular cells and organelles: the application of nanodrugs in acute kidney injury.

Acute kidney injury (AKI) is a common clinical syndrome with limited treatment options and high mortality rates. Proximal tubular epithelial cells (PTECs) play a key role in AKI progression. Subcellular dysfunctions, including mitochondrial, nuclear, endoplasmic reticulum and lysosomal dysfunctions, are extensively studied in PTECs. These studies have led to the development of potential therapeutic drugs. However, clinical development of those drugs faces challenges such as low solubility, short circulation time and severe systemic side effects. Nanotechnology provides a promising solution by improving drug properties through nanocrystallization and enabling targeted delivery to specific sites. This review summarizes advancements and limitations of nanoparticle-based drug-delivery systems in targeting PTECs and subcellular organelles, particularly mitochondria, for AKI treatment.

Advances and Opportunities in Nanoparticle Drug Delivery for Central Nervous System Disorders: A Review of Current Advances.

This narrative review provides an overview of the current advances, challenges, and opportunities in nanoparticle drug delivery for central nervous system (CNS) disorders. The treatment of central nervous system disorders is challenging due to the blood-brain barrier (BBB), which limits the delivery of therapeutic agents to the brain. Promising approaches to address these issues and improve the efficacy of CNS disease therapies are provided by nanoparticle-based drug delivery systems. Nanoparticles, such as liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles, can be modified to enhance targeting, stability, and drug-release patterns. They allow for the encapsulation of a variety of therapeutic compounds and can be functionalized with ligands or antibodies for active targeting, minimizing off-target effects. Additionally, nanoparticles can circumvent drug resistance processes and provide versatile platforms for applications that combine therapeutic and diagnostic functions. Although the delivery of CNS medications using nanoparticles has advanced significantly, there are still challenges to be resolved. These include understanding the BBB interactions, doing long-term safety studies, and scaling up the production. However, improvements in nanotechnology and a deeper comprehension of CNS disorders provide opportunities to enhance treatment results and address unmet medical requirements. Future research and ongoing clinical trials are required to further explore the potential of nanoparticle drug delivery for CNS disorders.

Nanoparticle-Based Treatment in Glioblastoma.

Glioblastoma (GB) is a malignant glioma associated with a mean overall survival of 12 to 18 months, even with optimal treatment, due to its high relapse rate and treatment resistance. The standardized first-line treatment consists of surgery, which allows for diagnosis and cytoreduction, followed by stereotactic fractionated radiotherapy and chemotherapy. Treatment failure can result from the poor passage of drugs through the blood-brain barrier (BBB). The development of novel and more effective therapeutic approaches is paramount to increasing the life expectancy of GB patients. Nanoparticle-based treatments include epitopes that are designed to interact with specialized transport systems, ultimately allowing the crossing of the BBB, increasing therapeutic efficacy, and reducing systemic toxicity and drug degradation. Polymeric nanoparticles have shown promising results in terms of precisely directing drugs to the brain with minimal systemic side effects. Various methods of drug delivery that pass through the BBB, such as the stereotactic injection of nanoparticles, are being actively tested in vitro and in vivo in animal models. A significant variety of pre-clinical studies with polymeric nanoparticles for the treatment of GB are being conducted, with only a few nanoparticle-based drug delivery systems to date having entered clinical trials. Pre-clinical studies are key to testing the safety and efficacy of these novel anticancer therapies and will hopefully facilitate the testing of the clinical validity of this promising treatment method. Here we review the recent literature concerning the most frequently reported types of nanoparticles for the treatment of GB.

Advancing Treatment Strategies: A Comprehensive Review of Drug Delivery Innovations for Chronic Inflammatory Respiratory Diseases.

Chronic inflammatory respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, present ongoing challenges in terms of effective treatment and management. These diseases are characterized by persistent inflammation in the airways, leading to structural changes and compromised lung function. There are several treatments available for them, such as bronchodilators, immunomodulators, and oxygen therapy. However, there are still some shortcomings in the effectiveness and side effects of drugs. To achieve optimal therapeutic outcomes while minimizing systemic side effects, targeted therapies and precise drug delivery systems are crucial to the management of these diseases. This comprehensive review focuses on the role of drug delivery systems in chronic inflammatory respiratory diseases, particularly nanoparticle-based drug delivery systems, inhaled corticosteroids (ICSs), novel biologicals, gene therapy, and personalized medicine. By examining the latest advancements and strategies in these areas, we aim to provide a thorough understanding of the current landscape and future prospects for improving treatment outcomes in these challenging conditions.

Hyperthermia-triggered biomimetic bubble nanomachines

Nanoparticle-based drug delivery systems have gained much attention in the treatment of various malignant tumors during the past decades. However, limited tumor penetration of nanodrugs remains a significant hurdle for effective tumor therapy due to the existing biological barriers of tumoral microenvironment. Inspired by bubble machines, here we report the successful fabrication of biomimetic nanodevices capable of in-situ secreting cell-membrane-derived nanovesicles with smaller sizes under near infrared (NIR) laser irradiation for synergistic photothermal/photodynamic therapy. Porous Au nanocages (AuNC) are loaded with phase transitable perfluorohexane (PFO) and hemoglobin (Hb), followed by oxygen pre-saturation and indocyanine green (ICG) anchored 4T1 tumor cell membrane camouflage. Upon slight laser treatment, the loaded PFO undergoes phase transition due to surface plasmon resonance effect produced by AuNC framework, thus inducing the budding of outer cell membrane coating into small-scale nanovesicles based on the pore size of AuNC. Therefore, the hyperthermia-triggered generation of nanovesicles with smaller size, sufficient oxygen supply and anchored ICG results in enhanced tumor penetration for further self-sufficient oxygen-augmented photodynamic therapy and photothermal therapy. The as-developed biomimetic bubble nanomachines with temperature responsiveness show great promise as a potential nanoplatform for cancer treatment.

NANOPARTICLE BASED DRUG DELIVERY SYSTEMS FOR TARGETING TUMOR MICRO ENVIRONMENT

Nanoparticle-based drug delivery systems have emerged as promising tools in cancer therapy, offering enhanced precision and effectiveness in targeting tumor cells while minimizing damage to healthy tissues. This review provides a comprehensive exploration of the tumor microenvironment, emphasizing its critical role in cancer progression. It highlights the significance of targeted drug delivery in improving treatment outcomes and introduces nanoparticle-based delivery systems as innovative strategies to address these challenges. The first section delves into various types of nanoparticles used for tumor targeting. Liposomes, known for their versatility and biocompatibility, are discussed alongside examples of liposome-based drug delivery systems tailored for tumor-specific applications. Polymeric nanoparticles, employing a range of polymers, offer unique advantages and applications in tumor targeting. Metallic nanoparticles, with distinctive properties, have shown promise in drug delivery systems designed to target tumors effectively.

Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors.

Immunotherapy has developed rapidly in solid tumors, especially in the areas of blocking inhibitory immune checkpoints and adoptive T-cell transfer for immune regulation. Many patients benefit from immunotherapy. However, the response rate of immunotherapy in the overall population are relatively low, which depends on the characteristics of the tumor and individualized patient differences. Moreover, the occurrence of drug resistance and adverse reactions largely limit the development of immunotherapy. Recently, the emergence of nanodrug delivery systems (NDDS) seems to improve the efficacy of immunotherapy by encapsulating drug carriers in nanoparticles to precisely reach the tumor site with high stability and biocompatibility, prolonging the drug cycle of action and greatly reducing the occurrence of toxic side effects. In this paper, we mainly review the advantages of NDDS and the mechanisms that enhance conventional immunotherapy in solid tumors, and summarize the recent advances in NDDS-based therapeutic strategies, which will provide valuable ideas for the development of novel tumor immunotherapy regimen.

CD38-targeted and erythrocyte membrane camouflaged nanodrug delivery system for photothermal and chemotherapy in multiple myeloma

Multiple myeloma (MM) is a malignant and incurable disease. Chemotherapy is currently the primary treatment option for MM. However, chemotherapeutic drugs can interrupt treatment because of serious side effects. Therefore, development of novel therapeutics for MM is essential. In this study, we designed and constructed an innovative nanoparticle-based drug delivery system, P-R@Ni3P-BTZ, and investigated its feasibility, effectiveness, and safety both in vitro and in vivo. P-R@Ni3P-BTZ is a nanocomposite that consists of two parts: (1) the drug carrier (Ni3P), which integrates photothermal therapy (PTT) with chemotherapy by loading bortezomib (BTZ); and (2) the shell (P-R), a CD38 targeting peptide P-modified red blood cell membrane nanovesicles. In vitro and in vivo, it was proven that P-R@Ni3P-BTZ exhibits remarkable antitumor effects by actively targeting CD38 + MM cells. P-R@Ni3P-BTZ significantly induces the accumulation of intracellular reactive oxygen species (ROS) and increases the apoptosis of MM cells, which underlies the primary mechanism of its antitumor effects. In addition, P-R@Ni3P exhibits good biocompatibility and biosafety, both in vitro and in vivo. Overall, P-R@Ni3P-BTZ is a specific and efficient MM therapeutic method.

Exploring the Microfluidic Production of Biomimetic Hybrid Nanoparticles and Their Pharmaceutical Applications.

Nanomedicines have made remarkable advances in recent years, addressing the limitations of traditional therapy and treatment methods. Due to their improved drug solubility, stability, precise delivery, and ability to target specific sites, nanoparticle-based drug delivery systems have emerged as highly promising solutions. The successful interaction of nanoparticles with biological systems, on the other hand, is dependent on their intentional surface engineering. As a result, biomimetic nanoparticles have been developed as novel drug carriers. In-depth knowledge of various biomimetic nanoparticles, their applications, and the methods used for their formulation, with emphasis on the microfluidic production technique, is provided in this review. Microfluidics has emerged as one of the most promising approaches for precise control, high reproducibility, scalability, waste reduction, and faster production times in the preparation of biomimetic nanoparticles. Significant advancements in personalized medicine can be achieved by harnessing the benefits of biomimetic nanoparticles and leveraging microfluidic technology, offering enhanced functionality and biocompatibility.

Nano-delivery systems as a promising therapeutic potential for epilepsy: Current status and future perspectives.

Epilepsy is a common chronic neurological disorder caused by aberrant neuronal electrical activity. Antiseizure medications (ASMs) are the first line of treatment for people with epilepsy (PWE). However, their effectiveness may be limited by their inability to cross the blood-brain barrier (BBB), among many other potential underpinnings for drug resistance in epilepsy. Therefore, there is a need to overcome this issue and, hopefully, improve the effectiveness of ASMs. Recently, synthetic nanoparticle-based drug delivery systems have received attention for improving the effectiveness of ASMs due to their ability to cross the BBB. Furthermore, exosomes have emerged as a promising generation of drug delivery systems because of their potential benefits over synthetic nanoparticles. In this narrative review, we focus on various synthetic nanoparticles that have been studied to deliver ASMs. Furthermore, the benefits and limitations of each nano-delivery system have been discussed. Finally, we discuss exosomes as potentially promising delivery tools for treating epilepsy.

In utero delivery of mRNA to the heart, diaphragm and muscle with lipid nanoparticles.

Nanoparticle-based drug delivery systems have the potential to revolutionize medicine, but their low vascular permeability and rapid clearance by phagocytic cells have limited their medical impact. Nanoparticles delivered at the in utero stage can overcome these key limitations due to the high rate of angiogenesis and cell division in fetal tissue and the under-developed immune system. However, very little is known about nanoparticle drug delivery at the fetal stage of development. In this report, using Ai9 CRE reporter mice, we demonstrate that lipid nanoparticle (LNP) mRNA complexes can deliver mRNA in utero, and can access and transfect major organs, such as the heart, the liver, kidneys, lungs and the gastrointestinal tract with remarkable efficiency and low toxicity. In addition, at 4 weeks after birth, we demonstrate that 50.99±5.05%, 36.62±3.42% and 23.7±3.21% of myofiber in the diaphragm, heart and skeletal muscle, respectively, were transfected. Finally, we show here that Cas9 mRNA and sgRNA complexed to LNPs were able to edit the fetal organs in utero. These experiments demonstrate the possibility of non-viral delivery of mRNA to organs outside of the liver in utero, which provides a promising strategy for treating a wide variety of devastating diseases before birth.

Nanotechnology-based Approaches for the Treatment of Toxocariasis: A Prospective Review

Toxocariasis, caused by Toxocara parasites, is a prevalent parasitic disease affecting millions of people worldwide. Conventional anthelmintic drugs for toxocariasis face challenges such as limited efficacy and potential adverse effects, necessitating exploring alternative therapeutic strategies. Nanotechnology has emerged as a promising approach for the treatment of toxocariasis. This prospective review provides an overview of the potential of nanotechnology in toxocariasis treatment and highlights critical advancements in the field. The current review aimed to provide an overview of toxocariasis and the current challenges in its treatment, such as limited efficacy and potential adverse effects. It emphasized the need for novel therapeutic approaches to overcome these limitations. The subsequent section focused on nanoparticle-based drug delivery systems, discussing the nanoparticles used in toxocariasis treatment, their advantages, and strategies for enhancing drug delivery efficiency. Nanotechnology in targeted therapy is a great strategy to treat toxocariasis. It explored targeting Toxocara parasites using nanoparticles, surface modifications for enhanced targeting, and controlled release and sustained drug delivery techniques. Nanodiagnostics and imaging techniques in diagnosing and monitoring provide promising futures for controlling toxocariasis. It explored the use of nanosensors for the sensitive detection of Toxocara parasites and various imaging modalities for parasite visualization. These advancements enabled timely intervention and personalized treatment strategies. Furthermore, the application of nanotechnology in vaccine development is fruitful for preventing toxocariasis. It highlights the use of nano vaccines for enhanced immune responses, controlled antigen delivery, and targeted immune cell activation. In conclusion, nanotechnology holds immense potential in the treatment of toxocariasis. Its unique features, such as targeted drug delivery, enhanced diagnostics, and improved vaccine efficacy, offer promising avenues for more effective and personalized approaches. Addressing evaluation, regulatory approval, cost-effectiveness, and scalability challenges is crucial for successful translation into clinical practice. The advancements in nanotechnology can potentially revolutionize toxocariasis treatment and improve patient outcomes.

Nuclear Delivery of Nanoparticle-Based Drug Delivery Systems by Nuclear Localization Signals.

Nanomedicine 2.0 refers to the next generation of nanotechnology-based medical therapies and diagnostic tools. This field focuses on the development of more sophisticated and precise nanoparticles (NPs) for targeted drug delivery, imaging, and sensing. It has been established that the nuclear delivery of NP-loaded drugs can increase their therapeutic efficacy. To effectively direct the NPs to the nucleus, the attachment of nuclear localization signals (NLSs) to NPs has been employed in many applications. In this review, we will provide an overview of the structure of nuclear pore complexes (NPCs) and the classic nuclear import mechanism. Additionally, we will explore various nanoparticles, including their synthesis, functionalization, drug loading and release mechanisms, nuclear targeting strategies, and potential applications. Finally, we will highlight the challenges associated with developing nucleus-targeted nanoparticle-based drug delivery systems (NDDSs) and provide insights into the future of NDDSs.

The surrogate scaffold method for quantifying molecular release kinetics from drug delivery systems

AbstractThe accurate determination of kinetics of therapeutic release from drug delivery vehicles is an essential step in the optimized design of such systems for biomedical and pharmaceutical applications. Most methods in current use for quantifying therapeutic release rates are developed to provide consistency, reproducibility, and ease of usage in a laboratory setting. These methods, however, do not necessarily mirror the release conditions when the drug delivery system comes into contact with the target tissue environment during application. As a result, the findings from these studies provide only comparative guidelines about the drug delivery rates and duration. Successful optimization of a drug delivery system requires complete, and accurate, knowledge about the release profile over an extended period of time to determine the initial release rate—including burst release if present, the rate of change of the release kinetics, and the maximum duration of delivery at a minimum therapeutic concentration level. We have developed an indirect method for the quantification of release kinetics suitable for nanoparticle‐based drug delivery systems that utilizes a hydrogel scaffold as a tissue surrogate to better emulate therapeutic delivery into a target tissue environment. Details of the method and its application to the release of an angiogenic peptide from a nanoparticle emulsion are provided in this communication.

Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.

Cantharidin (CTD), a natural compound derived from Mylabris, is widely used in traditional Oriental medicine for its potent anticancer properties. However, its clinical application is restricted due to its high toxicity, particularly towards the liver. This review provides a concise understanding of the hepatotoxic mechanisms of CTD and highlights novel therapeutic strategies to mitigate its toxicity while enhancing its anticancer efficacy. We systematically explore the molecular mechanisms underlying CTD-induced hepatotoxicity, focusing on the involvement of apoptotic and autophagic processes in hepatocyte injury. We further discuss the endogenous and exogenous pathways implicated in CTD-induced liver damage and potential therapeutic targets. This review also summarizes the structural modifications of CTD derivatives and their impact on anticancer activity. Additionally, we delve into the advancements in nanoparticle-based drug delivery systems that hold promise in overcoming the limitations of CTD derivatives. By offering valuable insights into the hepatotoxic mechanisms of CTD and outlining potential avenues for future research, this review contributes to the ongoing efforts to develop safer and more effective CTD-based therapies.

Design of experiments in the optimization of nanoparticle-based drug delivery systems.

Design of experiment (DoE) is a powerful statistical technique used for variable screening and optimization. It is based on the simultaneous variation of multiple factors with the objective of finding the configuration of parameters that optimizes one or more outputs of interest, while using the minimal number of experimental runs required for testing, resulting very cost and time-efficient. Despite the high potential offered by this approach for innovation and process optimization, DoE is still only marginally applied in the field of nanomedicine and often its rationale application and analysis result is difficult to grasp by many. In this review, we discuss some of the latest applications of DoE in the formulation of nanovectors used for drug delivery across many different applications. First, we introduce general principles of DoE to the reader, which are indispensable to understand the works we report. Then, we give particular attention to the process variables, the specific designs, and the readouts used for process analysis and optimization for different classes of nanovectors. Finally, we try to delve into the current shortcomings of DoE application and possible future directions that could be employed to further improve the information that can be derived from this approach.

60. Insulin Like Growth Factor 1 Nanoparticle Based Drug Delivery System for Peripheral Nerve Injury in Non-human Primates

60. Insulin Like Growth Factor 1 Nanoparticle Based Drug Delivery System for Peripheral Nerve Injury in Non-human Primates