Nanoparticulate Drug Delivery Systems Research Articles

Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering

The versatile natural polymer, collagen, has gained vast attention in biomedicine. Due to its biocompatibility, biodegradability, weak antigenicity, biomimetics and well-known safety profile, it is widely used as a drug, protein and gene carrier, and as a scaffold matrix in tissue engineering. Nanoparticles develop favorable chemical and physical properties such as increased drug half-life, improved hydrophobic drug solubility and controlled and targeted drug release. Their reduced toxicity, controllable characteristics of scaffolds and stimuli-responsive behavior make them suitable in regenerative medicine and tissue engineering. Collagen associates and absorbs nanoparticles leading to significant impacts on their biological functioning in any biofluid. This review will discuss collagen nanoparticle preparation methods and their applications and developments in drug delivery systems and tissue engineering.

Shaping nanoparticle diffusion through biological barriers to drug delivery

Nanoparticle drug delivery systems encounter many biological barriers, such as the extracellular matrix and mucus gels, that they must bypass to gain access to target cells. A design parameter that has recently gained attention is nanoparticle shape, as it has been shown elongated rod–shaped nanoparticles achieve higher diffusion rates through biological gels. However, the optimal dimensions of rod-shaped nanoparticles to enhance this effect has yet to be established. To systematically approach this, rod-shaped nanoparticles were synthesized by mechanically stretching 100 ​nm, 200 ​nm, and 500 ​nm spherical nanoparticles. Transmission electron microscopy confirmed this procedure yields a significant fraction of elongated rods and remaining spheres could be removed by centrifugation. Fluorescent microscopy and multiple particle tracking analysis was then used to characterize rod-shaped and spherical nanoparticle diffusion in MaxGel®, a model extracellular matrix hydrogel. When dispersed in MaxGel, we found rod-shaped nanoparticles exhibited the greatest enhancement in diffusion rate when their length far exceeds the average hydrogel network size. These results further establish the importance of shape as a design criterion to improve nanoparticle-based drug delivery systems.

Nano Drug Delivery Platforms for Dental Application: Infection Control and TMJ Management-A Review.

The oral cavity is an intricate environment subjected to various chemical, physical, and thermal injuries. The effectiveness of the local and systemically administered drugs is limited mainly due to their toxicities and poor oral bioavailability that leads to the limited effectiveness of the drugs in the target tissues. To address these issues, nanoparticle drug delivery systems based on metals, liposomes, polymeric particles, and core shells have been developed in recent years. Nano drug delivery systems have applications in the treatment of patients suffering from temporomandibular joint disorders such as preventing degeneration of cartilage in patients suffering from rheumatoid arthritis and osteoarthritis and alleviating the pain along with it. The antibacterial dental applications of nano-drug delivery systems such as silver and copper-based nanoparticles include these agents used to arrest dental caries, multiple steps in root canal treatment, and patients suffering from periodontitis. Nanoparticles have been used in adjunct with antifungals to treat oral fungal infections such as candida albicans in denture wearers. Acyclovir being the most commonly used antiviral has been used in combination with nanoparticles against an array of viral infections such as the herpes simplex virus. Nanoparticles based combination agents offer more favorable drug release in a controlled manner along with efficient delivery at the site of action. This review presents an updated overview of the recently developed nanoparticles delivery systems for the management of temporomandibular joint disorders along with the treatment of different oral infections.

Design and development of 5-fluorouracil loaded biodegradable magnetic microspheres as site-specific drug delivery vehicle for cancer therapy

The major limitation of present cancer chemotherapeutic agents is the poor selectivity of anti-cancer drug and the resultant toxicity. To circumvent this limitation intense research is currently focused on development of controlled and targeted drug delivery systems. Drug delivery systems are based on nanoscale and micro-scaledrug delivery processes with potential advantage of enhanced accuracy of tumor targeting. Among the nanoparticulate drug delivery systems magnetic iron oxide nanoparticles (MIONs) demonstrate efficacy in terms of tissue targeting and biocompatibility. The polymer coating could be optimized for required rate of release of the drug. The magnetic iron nanoparticles could be directed to a target tissue through application of an external magnetic field. Consequent to the site-specific delivery of the drug, the therapeutic efficacy of the chemotherapeutic agent can be evaluated in terms of clinical outcomes. This study reports synthetic preparation of magnetic poly-(D, L-lactide-co-glycolic acid) (PLGA) microspheres loaded with an anticancer drug 5-Fluorouracil (5-FLU). The nanoparticlulate drug loaded microspheres were synthesized and stabilized as water-in-oil-in-water (W1-O-W2) ternary emulsion system via solvent evaporation. The nanoparticulate system was characterized by X-ray diffraction analysis, Fourier Transform Infrared spectroscopy and electron microscopy. The magnetic nanoparticulate system also exhibited pH-dependent release of 5-fluorouracil.

Approved and marketed nanoparticles for disease targeting and applications in COVID-19

Abstract Nano-based systems can be used to transport active medicinal products to specific parts of the body. Most challenges with drug delivery, such as low water solubility and poor bioavailability, can be solved using nanotechnology. In addition, nanoparticles can overcome various physiological obstacles to increase load distribution to desired sites. Nanoparticles can carry a load of medication or therapeutic agent, such as a DNA-related substance, to enhance distribution time and deliver the drug to the target site in either a nonspecific (through enhanced permeability and retention (EPR)) or specific (through binding specific target receptors) manner. Moreover, nanoparticle drug delivery systems have been employed in the clinic since the early 1990s. Since then, the field of nanomedicine has developed with growing technical needs to improve the delivery of various medications. Over these past decades, newer generations of nanoparticles have emerged that are capable of conducting new delivery activities that could enable therapy via innovative therapeutic modalities. This review highlights different types of approved and currently marketed nanoparticles, such as nanocrystals, liposomes, lipid nanoparticles, PEGylated polymeric nanoparticles, protein-based nanoparticles, and metal-based nanoparticles. Furthermore, it explores the use of vaccine-loaded nanoparticles for COVID-19 prophylaxis.

Pharmaceutical Applications of Supercritical Fluid Extraction of Emulsions for Micro-/Nanoparticle Formation.

Micro-/nanoparticle formulations containing drugs with or without various biocompatible excipients are widely used in the pharmaceutical field to improve the physicochemical and clinical properties of the final drug product. Among the various micro-/nanoparticle production technologies, emulsion-based particle formation is the most widely used because of its unique advantages such as uniform generation of spherical small particles and higher encapsulation efficiency (EE). For this emulsion-based micro-/nanoparticle technology, one of the most important factors is the extraction efficiency associated with the fast removal of the organic solvent. In consideration of this, a technology called supercritical fluid extraction of emulsions (SFEE) that uses the unique mass transfer mechanism and solvent power of a supercritical fluid (SCF) has been proposed to overcome the shortcomings of several conventional technologies such as solvent evaporation, extraction, and spray drying. This review article presents the main aspects of SFEE technology for the preparation of micro-/nanoparticles by focusing on its pharmaceutical applications, which have been organized and classified according to several types of drug delivery systems and active pharmaceutical ingredients. It was definitely confirmed that SFEE can be applied in a variety of drugs from water-soluble to poorly water-soluble. In addition, it has advantages such as low organic solvent residual, high EE, desirable release control, better particle size control, and agglomeration prevention through efficient and fast solvent removal compared to conventional micro-/nanoparticle technologies. Therefore, this review will be a good resource for determining the applicability of SFEE to obtain better pharmaceutical quality when researchers in related fields want to select a suitable manufacturing process for preparing desired micro-/nanoparticle drug delivery systems containing their active material.

Efficacy of miR-122 Nanoparticle Drug Delivery System on the Patients with Drug-Induced Liver Injury

In order to explore the effect of MiR-122 nanoparticle (NP) drug delivery system (NPDDS) on the condition and curative effect of patients with drug-induced liver injury (DILI). The phosphate buffered saline solution was added to the solution of Monoammonium Glycyrrhizanate (MAG) NPs to make the suspension. Then, 50 μL of the MAG β-cyclodextrin star-shaped cationic polymer solution was added to the 100 μg/mL MiR-122 solution and form MAG/MiR-122 co-loaded NPs. 40 cases of acute DILI patients in hospital were selected as the research subjects. Control group, polymer group, drug-loaded group, and co-loaded group were set up, and fluorescence quantitative PCR was employed to measure the expression level of MiR-122 in the cells. The untreated DILI cells were set as control group, while the MAG/MiR-122 co-loaded NPs-treated DILI cells were set as treatment group. The treatment effects of the two groups were analyzed and compared. The results showed that the MAG/MiR co-loaded NPs prepared were of regular round shape and uniform particle size distribution. The expression of MiR-122 was low in control group, and its content in injured cells was extremely low. The expression of MiR-122 in the co-loaded group was superior to drug-loaded group. The effective rate of drug treatments in treatment group was significantly superior to control group, and the differences were substantial (P < 0.05). The number of red blood cells (RBC) of treatment group decreased notably relative to controls, while differences on white blood cells (WBC) and platelets (PLT) between two groups were not considerable (P > 0.05). In conclusion, MAG/MiR co-loaded NPs can effectively improve the therapeutic effect of DILI. Moreover, early DILI screening can be implemented by detecting the expression level of MiR-122 in the cells of DILI patients.

Dosing extracellular vesicles.

Extracellular vesicles (EVs) are natural nanoparticles containing biologically active molecules. They are important mediators of intercellular communication and can be exploited therapeutically by various bioengineering approaches. To accurately determine the therapeutic potential of EVs in pre-clinical and clinical settings, dependable dosing strategies are of utmost importance. However, the field suffers from inconsistencies comprising all areas of EV production and characterisation. Therefore, a standardised and well-defined process in EV quantification, key to reliable therapeutic EV dosing, remains to be established. Here, we examined 64 pre-clinical studies for EV-based therapeutics with respect to their applied EV dosing strategies. We identified variations in effective dosing strategies irrespective of the applied EV purification method and cell source. Moreover, we found dose discrepancies depending on the disease model, where EV doses were selected without accounting for published EV pharmacokinetics or biodistribution patterns. We therefore propose to focus on qualitative aspects when dosing EV-based therapeutics, such as the potency of the therapeutic cargo entity. This will ensure batch-to-batch reliability and enhance reproducibility between applications. Furthermore, it will allow for the successful benchmarking of EV-based therapeutics compared to other nanoparticle drug delivery systems, such as viral vector-based or lipid-based nanoparticle approaches.

Lipid Nanoparticulate Drug Delivery Systems: Recent Advances in the Treatment of Skin Disorders.

The multifunctional role of the human skin is well known. It acts as a sensory and immune organ that protects the human body from harmful environmental impacts such as chemical, mechanical, and physical threats, reduces UV radiation effects, prevents moisture loss, and helps thermoregulation. In this regard, skin disorders related to skin integrity require adequate treatment. Lipid nanoparticles (LN) are recognized as promising drug delivery systems (DDS) in treating skin disorders. Solid lipid nanoparticles (SLN) together with nanostructured lipid carriers (NLC) exhibit excellent tolerability as these are produced from physiological and biodegradable lipids. Moreover, LN applied to the skin can improve stability, drug targeting, occlusion, penetration enhancement, and increased skin hydration compared with other drug nanocarriers. Furthermore, the features of LN can be enhanced by inclusion in suitable bases such as creams, ointments, gels (i.e., hydrogel, emulgel, bigel), lotions, etc. This review focuses on recent developments in lipid nanoparticle systems and their application to treating skin diseases. We point out and consider the reasons for their creation, pay attention to their advantages and disadvantages, list the main production techniques for obtaining them, and examine the place assigned to them in solving the problems caused by skin disorders.

Advances in Nanoparticle Drug Delivery Systems for Anti-Hepatitis B Virus Therapy: A Narrative Review.

Chronic hepatitis B (CHB) is an infectious viral disease that is prevalent worldwide. Traditional nucleoside analogues, as well as the novel drug targets against hepatitis B virus (HBV), are associated with certain critical factors that influence the curative effect, such as biological stability and safety, effective drug delivery, and controlled release. Nanoparticle drug delivery systems have significant advantages and have provided a basis for the development of anti-HBV strategies. In this review, we aim to review the advances in nanoparticle drug delivery systems for anti-hepatitis B virus therapy by summarizing the relevant literature. First, we focus on the characteristics of nanoparticle drug delivery systems for anti-HBV therapy. Second, we discuss the nanoparticle delivery systems for anti-HBV nucleoside drugs, gene-based drugs, and vaccines. Lastly, we provide an overview of the prospects for nanoparticle-based anti-HBV agents.

Nanoparticulate drug delivery systems: A revolution in design and development of drugs

The recent developments in nanoparticle-based drug formulations have been helping to address issues around treating challenging diseases. Nanoparticles come in different sizes but usually vary between 100nm to 500nm. For the past few years there has been research going on in the area of drug delivery using particulate delivery systems. Various drug molecules have been modified for both pharmacokinetic and pharmacodynamic properties using nanoparticles as physical approach. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimizing side effects. Here, we review various aspects of nanoparticle formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules and therapeutic genes.
 Keywords: nanoparticles, applications in delivery, Liposomes, Dendrimers

Development and optimization of paclitaxel loaded Eudragit/PLGA nanoparticles by simplex lattice mixture design: Exploration of improved hemocompatibility and in vivo kinetics

Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77–214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55–163,071.15 h*ng/mL), longer half-lives (5.80–6.35 h) and extended mean residence times (6.05–8.54 h) in comparison to PTX solution (p < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects.

Research progress on therapeutic potential of quercetin

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.

Engineered Nanoparticles for Prevention against CoVID-19 Infection

The sudden emergence of novel coronavirus CoVID-19 in China during the end of last year and its outburst all around the globe thereafter have raised serious questions about their instant management and diagnostic measures as it is infecting humans around in an exponential manner. The implementation of nanotechnology could perhaps ingenerate the rising distress due to the spread of the disease as the conventional antiviral drugs just control the symptoms. Nanoparticles drug delivery systems are engineered technologies that use nanoparticles for targeted drug delivery and controlled release of therapeutic agents. Nanoparticles based approach can replace the treatment with a more promising one that could meet these challenges. Understanding molecular pathogenesis of CoVID-19 infection is very important to exploit the nanoparticles to fight against it. A lot of nanostructures have been developed with antiviral and antibacterial properties for a variety of drug delivery and biomedical applications. The need of the hour is to exploit nano research to develop effective diagnostics tools, drugs, vaccines to treat and prohibit infection. In this paper an attempt has been made to understand the role and potential of various nanoparticles to inhibit CoVID-19 infection and its toxicity effects.

Permeation Challenges of Drugs for Treatment of Neurological Tuberculosis and HIV and the Application of Magneto-Electric Nanoparticle Drug Delivery Systems.

The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-invasive approach for the delivery of drugs into the CNS. These nanoparticles (NPs) can create localized transient changes in the permeability of the cells of the BBB by inducing electroporation. MENs can be applied to deliver antiretrovirals and antibiotics towards the treatment of human immunodeficiency virus (HIV) and tuberculosis (TB) infections in the CNS. This review focuses on the drug permeation challenges and reviews the application of MENs for drug delivery for these diseases. We conclude that MENs are promising systems for effective CNS drug delivery and treatment for these diseases, however, further pre-clinical and clinical studies are required to achieve translation of this approach to the clinic.

Recent Advances of Microfluidic Platforms for Controlled Drug Delivery in Nanomedicine.

Nanomedicine drug delivery systems hold great potential for the therapy of many diseases, especially cancer. However, the controlled drug delivery systems of nanomedicine bring many challenges to clinical practice. These difficulties can be attributed to the high batch-to-batch variations and insufficient production rate of traditional preparation methods, as well as a lack of technology for fast screening of nanoparticulate drug delivery structures with high correlation to in vivo tests. These problems may be addressed through microfluidic technology. Microfluidics, for example, can not only produce nanoparticles in a well-controlled, reproducible, and high-throughput manner, but it can also continuously create three-dimensional environments to mimic physiological and/or pathological processes. This overview gives a top-level view of the microfluidic devices advanced to put together nanoparticulate drug delivery systems, including drug nanosuspensions, polymer nanoparticles, polyplexes, structured nanoparticles and therapeutic nanoparticles. Additionally, highlighting the current advances of microfluidic systems in fabricating the more and more practical fashions of the in vitro milieus for fast screening of nanoparticles was reviewed. Overall, microfluidic technology provides a promising technique to boost the scientific delivery of nanomedicine and nanoparticulate drug delivery systems. Nonetheless, digital microfluidics with droplets and liquid marbles is the answer to the problems of cumbersome external structures, in addition to the rather big pattern volume. As the latest work is best at the proof-of-idea of liquid-marble-primarily based on totally virtual microfluidics, computerized structures for developing liquid marble, and the controlled manipulation of liquid marble, including coalescence and splitting, are areas of interest for bringing this platform toward realistic use.

Formulation and Evaluation of Miconazole Nitrate Loaded Nanoparticles for Topical Delivery

The aim of the present work was to formulate and evaluate Miconazole nitrate (MN) polymeric nanoparticles (NPs) for systemic delivery of the active ingredient after topical administration. The Solvent evaporation approach was used to make nanoparticles for topical delivery of MN. Particle size, entrapment efficiency and SEM were all measured in MN-SLN. A consistent size distribution (PI 0.300) was used to generate aqueous NPs dispersions with a mean particle size less than 250 nm. After 3 months of storage, the produced semi-solid systems had a mean particle size of less than 250 nm and a PI of less than 0.500. The F5 formulation was been chosen as the model formulation from among the nine nanoparticle formulations developed (F1 to F9). The reason for this was that, according to the ICH stability guidelines, formulation F5 was judged to be optimal and stable. The F5 formulations of miconazole nanoparticles shows the highest entrapment efficiency (93.28%) and drug loading (86.64%). In conclusion, there are two major advantages of using miconazole nanoparticle drug delivery systems. i.e., they are topical preparations that assemble in the hair follicles and wrinkles to produce a systemic and local action. It is possible that nanoparticles will be the most effective treatment for fungal skin infections.

Obstacles and Recommendations for Clinical Translation of Nanoparticle System-Based Targeted Alpha-Particle Therapy.

The rationale for application of nanotechnology in targeted alpha therapy (TAT) is sound. However, the translational strategy requires attention. Formulation of TAT in nanoparticulate drug delivery systems has the potential to resolve many of the issues currently experienced. As α-particle emitters are more cytotoxic compared to beta-minus-emitting agents, the results of poor biodistribution are more dangerous. Formulation in nanotechnology is also suggested to be the ideal solution for containing the recoil daughters emitted by actinium-225, radium-223, and thorium-227. Nanoparticle-based TAT is likely to increase stability, enhance radiation dosimetry profiles, and increase therapeutic efficacy. Unfortunately, nanoparticles have their own unique barriers towards clinical translation. A major obstacle is accumulation in critical organs such as the spleen, liver, and lungs. Furthermore, inflammation, necrosis, reactive oxidative species, and apoptosis are key mechanisms through which nanoparticle-mediated toxicity takes place. It is important at this stage of the technology’s readiness level that focus is shifted to clinical translation. The relative scarcity of α-particle emitters also contributes to slow-moving research in the field of TAT nanotechnology. This review describes approaches and solutions which may overcome obstacles impeding nanoparticle-based TAT and enhance clinical translation. In addition, an in-depth discussion of relevant issues and a view on technical and regulatory barriers are presented.

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells’ nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.

Targeting Nanoparticles to Bioengineered Human Vascular Networks.

Pharmacotherapy of vascular anomalies has limited efficacy and potentially limiting toxicity. Targeted nanoparticle (NP) drug delivery systems have the potential to accumulate within tissues where the vasculature is impaired, potentially leading to high drug levels (increased efficacy) in the diseased tissue and less in off-target sites (less toxicity). Here, we investigate whether NPs can be used to enhance drug delivery to bioengineered human vascular networks (hVNs) that are a model of human vascular anomalies. We demonstrate that intravenously injected phototargeted NPs enhanced accumulation of NPs and the drug within hVNs. With phototargeting we demonstrate 17 times more NP accumulation within hVNs than was detected in hVNs without phototargeting. With phototargeting there was 10-fold more NP accumulation within hVNs than in any other organ. Phototargeting resulted in a 6-fold increase in drug accumulation (doxorubicin) within hVNs in comparison to animals injected with the free drug. Nanoparticulate approaches have the potential to markedly improve drug delivery to vascular anomalies.