Drug Targeting Applications Research Articles

Advances in Drug Targeting, Drug Delivery, and Nanotechnology Applications: Therapeutic Significance in Cancer Treatment

In the 21st century, thanks to advances in biotechnology and developing pharmaceutical technology, significant progress is being made in effective drug design. Drug targeting aims to ensure that the drug acts only in the pathological area; it is defined as the ability to accumulate selectively and quantitatively in the target tissue or organ, regardless of the chemical structure of the active drug substance and the method of administration. With drug targeting, conventional, biotechnological and gene-derived drugs target the body’s organs, tissues, and cells that can be selectively transported to specific regions. These systems serve as drug carriers and regulate the timing of release. Despite having many advantageous features, these systems have limitations in thoroughly treating complex diseases such as cancer. Therefore, combining these systems with nanoparticle technologies is imperative to treat cancer at both local and systemic levels effectively. The nanocarrier-based drug delivery method involves encapsulating target-specific drug molecules into polymeric or vesicular systems. Various drug delivery systems (DDS) were investigated and discussed in this review article. The first part discussed active and passive delivery systems, hydrogels, thermoplastics, microdevices and transdermal-based drug delivery systems. The second part discussed drug carrier systems in nanobiotechnology (carbon nanotubes, nanoparticles, coated, pegylated, solid lipid nanoparticles and smart polymeric nanogels). In the third part, drug targeting advantages were discussed, and finally, market research of commercial drugs used in cancer nanotechnological approaches was included.

Research on the application of micro-robotics in the drug delivery field

Abstract. Drug delivery has been one of the hotspots of research in the field of pharmacy. Delivering drugs to the target location more accurately and efficiently is a problem that researchers have been thinking of facing. The invention of the microrobot has led to greater convenience in the field of micromanipulation. Microrobots have demonstrated exceptional promise and significant benefits in the field of medication delivery in recent years, owing to their versatility, low invasiveness, and controllability. This paper comprehensively reviews the research on microrobots for drug delivery applications. First, we summarize the microrobots in vivo motion technology from the propulsion mode perspective and discuss its effects. Subsequently, we analyze the new technologies in the field related to microrobots used for drug-targeting applications and explore the release method of the drug to reach the target location. Finally, synthesizing the analysis results, we give the problems and future development of microrobot applications in the field of drug delivery.

Ligand-Based targeting in drug delivery system

Targeted drug delivery system has come up as a new approach that increase the effectiveness of the drug while reducing the side effects of cancer therapy. This review focuses on the application of ligand-based drug targeting, especially antibodies-drug conjugates in the case of ovarian cancer and folate-receptor targeting in the case for tumor cells. This review will provide analytical insights about the effectiveness of two approaches on improving bioavailability, targeting specific tumor cells, and enhancing drug carrying capacity. The findings show that folate receptor targeting does has significant potential in enhancing curcumin’s anticancer activity. However, there are still challenges such as rapid decomposition of curcumin. This review also highlights the need for future experiments and research to consolidate the effectiveness of the drug delivery system and explore their potential in broader clinical environment.

Endocytosis efficiency and targeting ability by the cooperation of nanoparticles.

Cooperative wrapping of nanoparticles (NPs) with small sizes is an important pathway for the uptake of NPs by cell membranes. However, the cooperative wrapping efficiency and the effects of NPs' rigidity remain ambiguous. With the aid of computer simulations, we show that the complete wrapping mechanism of cooperative endocytosis is that the aggregation of NPs leads to greater wrapping forces than the single NP case, which triggers the increase of the wrapping degree and in turn further increases the wrapping forces until they are finally fully taken up. The effects of the NP size, initial distance, interaction strength, arrangement and stiffness on cooperative endocytosis were systematically studied. The cooperative wrapping efficiency increases as the NP radius increases. Hexagonal close packed NPs have the highest internalization efficiency. When the interactions are strong, softer NPs exhibit higher endocytosis efficiency. We further propose two strategies by combining NPs with different wrapping properties for targeting applications. By combining two NPs decorated with different types of ligands, the combination NPs can only be fully endocytosed by the cell membrane with two cognate types of receptors and adhere to the normal cell membrane with only one type of receptor. We also design composite NPs using a large NP non-covalently decorated with several small NPs. By harnessing the competition between the ligand-receptor interactions and the excluded volume interactions between the small NPs and the lipid membrane, the composite NPs have targeting ability towards the cancer cell membrane. The design concept of combining NPs with different wrapping properties for drug targeting applications may be very promising in biomedicine.

Pulsatile blood flow simulations of magnetic drug targeting (MDT) for drug particles dispersion through stenosis asymmetric and symmetric vessels

Magnetic drug delivery has emerged as an innovative strategy for addressing medical conditions like tumors and vascular occlusions. In this study, we delve into the influence of magnetic fields on three-dimensional models representing various vessel configurations, including unobstructed, asymmetric, and symmetric vessels. We take into account critical factors such as non-Newtonian viscosity, pulsatile flow, and the presence of vessel obstructions. By investigating drug particles ranging from 1 to 4 µm in diameter, our findings illuminate the central role that magnetic particles play in Magnetic Drug Targeting (MDT). Importantly, we observe a substantial enhancement in drug particle capture efficiency in the presence of a magnetic field, particularly for larger particle diameters. Nevertheless, this efficiency saturates at 100% for diameters exceeding 3 µm due to particle–wall interactions. Interestingly, within potential obstruction areas, particle capture efficiency exhibits a nuanced relationship with diameter. Even at a diameter of 4 µm, the magnetic field's influence on vessel walls leads to particle capture before reaching obstructions, thus reducing efficiency. Comparing scenarios without a magnetic field, it is found that symmetrical obstructions yield higher capture efficiency compared to asymmetrical vessels, and asymmetric vessels outperform their smoother counterparts. Moreover, the presence of vessel obstructions amplifies drug particle capture efficiency. Consequently, our simulations unveil significant potential for the application of MDT in the treatment of atherosclerosis. From a physics perspective, these results offer promising prospects for the application of Magnetic Drug Targeting in the realm of cardiovascular diseases.

Folic Acid-Modified Ibrutinib-Loaded Silk Fibroin Nanoparticles for Cancer Cell Therapy with Over-Expressed Folate Receptor.

The anticancer drug ibrutinib (IB), also known as PCI-32765, is a compound that irreversibly inhibits Bruton's tyrosine kinase (BTK) and was initially developed as a treatment option for B-cell lineage neoplasms. Its action is not limited to B-cells, as it is expressed in all hematopoietic lineages and plays a crucial role in the tumor microenvironment. However, clinical trials with the drug have resulted in conflicting outcomes against solid tumors. In this study, folic acid-conjugated silk nanoparticles were used for the targeted delivery of IB to the cancer cell lines HeLa, BT-474, and SKBR3 by exploiting the overexpression of folate receptors on their surfaces. The results were compared with those of control healthy cells (EA.hy926). Cellular uptake studies confirmed total internalization of the nanoparticles functionalized by this procedure in the cancer cells after 24 h, compared to nanoparticles not functionalized with folic acid, suggesting that cellular uptake was mediated by folate receptors overexpressed in the cancer cells. The results indicate that the developed nanocarrier can be used for drug targeting applications by enhancing IB uptake in cancer cells with folate receptor overexpression.

OXYMATRINE (AN INHIBITOR OF HSPA8) REDUCES BINDING OF VGF DERIVED BIOACTIVE PEPTIDE TLQP-21 TO THE SURFACE OF LIVE SH-SY5Y CELLS

Use of active site-targeting inhibitor is an effective approach leading to pharmacological inventions. Heat shock cognate protein A8 (HSPA8) has been found as a receptor of VGF derived bioactive peptide TLQP-21 in SH-SY5Y cells. So, it was of much interest to carry out this study in order to observe whether Oxymatrine (OMTR), an inhibitor of HSPA8, inhibits the binding of TLQP-21 to the surface of intact, live SH-SY5Y cells. The results confirmed, as expected, that OMTR reduces the binding of TLQP-21 to the surface of intact, live SH-SY5Y cells, with a strong conclusion that the binding of TLQP-21 to the surface of SH-SY5Y cell model was through HSPA8. The inhibition efficacy of OMTR potentiates its application in drug targeting.

Magnetic Forces by Permanent Magnets to Manipulate Magnetoresponsive Particles in Drug-Targeting Applications.

This study presents preliminary computational and experimental findings on two alternative permanent magnet configurations helpful for magnetic drug administration in vivo. A numerical simulation and a direct experimental measurement of the magnetic induction on the magnet system's surface were used to map the magnetic field. In addition, the ferrite-type (grade Y35) and permanent neodymium magnets (grade N52) to produce powerful magnetic forces were also examined analytically and quantitatively. Ansys-Maxwell software and Finite Element Method Magnetism (FEMM) version 4.2 were used for all numerical computations in the current investigation. For both magnets, the generated magnetic fields were comparatively studied for targeting Fe particles having a diameter of 6 μm. The following findings were drawn from the present investigation: (i) the particle deposition on the vessel wall is greatly influenced by the intensity of the magnetic field, the magnet type, the magnet size, and the magnetic characteristics of the micro-sized magnetic particles (MSMPs); (ii) ferrite-type magnets might be employed to deliver magnetoresponsive particles to a target location, even if they are less powerful than neodymium magnets; and (iii) the results from the Computational Fluid Dynamics( CFD) models agree well with the measured magnetic field induction, magnetic field strength, and their fluctuation with the distance from the magnet surface.

Alginate based Nanoparticles and Its Application in Drug Delivery Systems

Nanoparticulate systems made of biopolymers encompass promising properties as carriers and adjuvant for drug delivery. Alginate is one of the most widely investigated biomaterials in the field of nanoparticulate drug delivery due to its biodegradability, biocompatibility, and bioadhesivity. Alginate nanoparticles for drug delivery can be prepared through spray drying, ionic gelation, emulsification, covalent cross-linking, polyelectrolyte complexation, self-assembling, etc. Alginate is an extensively utilized biopolymer in multiple applications due to its gelling property and chemical structure with hydroxyl and carboxylate moieties. The biocompatibility, biodegradability of alginate, and solubility in water have broadened up research perspectives in material, and biomedical sciences. Study of alginate-based nanoparticles, nanoaggregates, and nanofibers initiated recently. In the present review, the physicochemical properties of alginate, which enabled its use as a pharmaceutical excipient and as nanocarriers in drug delivery, have been reviewed. A special insight has been given on the modern advances of alginate nanoparticles in drug delivery and drug targeting applications. Besides this, limitations of alginate as nanocarriers in drug delivery and the future perspectives on how to augment utilization in the pharmaceutical nanotechnology have also been reviewed.

The inclination of magnetic dipole effect and nanoscale exchange of heat of the Cross nanofluid

Nanoscale energy exchange and movement of fluid by Lorentz force is the most recent problem that has a strong connection with applied mathematics due to the consumption of energy. Imposing the inclination of Magnetic dipole in the fluid has abundant applications in magnetic drug engineering, astrophysics, sensors, geophysics, cosmology, and targeting. This study is associated with the exchange of energy under the influence of the inclination of Magnetic dipole with cylinder geometry. The Cross nanofluid mathematical model is launched to carry the nanoscale energy exchange with temperature-dependent thermal conductivity. The permeable cylinder geometry along with the different effects is provided during the expanding/contracting cylinder. Whereas Cross fluid helps to investigate the problem in shear thinning/thickening regions. The numerical representations of the problem are provided via the BVP4C scheme.

A Review on Formulation and Evaluation of Nanoniosomal Topical gel of Paclitaxel for skin cancer

Cancer is the second leading cause of death in the world and one of the major public health problems. Despite the great advances in cancer therapy, the incidence and mortality rates of cancer remain high. Therefore, the goal for more efficient and less toxic cancer treatment strategies is still at the forefront of current research. Despite these efforts, cancer drug research remains a remarkably challenging field, and therapeutic innovations have not yet achieved expected clinical results. However, the physiopathology of the disease is now better understood, and the discovery of novel molecular targets has refreshed the expectations of developing improved treatments. Paclitaxel (PCT) is a chemotherapeutic agent used as a first-line treatment for a wide range of cancers, such as lung, ovarian, breast, prostate, head, and neck cancers, and AIDS-related Kaposi sarcoma. Currently, the marketed forms of Paclitaxel are intravenous formulations. Oral administration of Paclitaxel is unfortunately hampered due to its low bioavailability. This is explained by its low aqueous solubility, low permeability, high affinity for cytochrome P450 and P-glycoprotein. As another approach, drug carrier systems are extensively studied to enhance oral Paclitaxel bioavailability and reduce side effects. The niosomes provides several important advantages over conventional drug therapy. Structurally, niosomes are similar to liposomes, in that they are also made up of a bilayer. However, the bilayer in the case of niosomes is made up of non-ionic surface-active agents rather than phospholipids as seen in case of liposomes. Niosome nanoparticles are among these drug delivery systems, which have numerous applications in drug delivery and targeting. Niosomes are frequently used for loading drugs serving different purposes (e.g., anticancer, antiviral, and antibacterial agents). The aim of this review is to evaluate the extent of nanotherapeutics used in anti-cancer activity.

Liquid–Liquid Encapsulation of Ferrofluid Using Magnetic Field

AbstractEncapsulated magnetic microdroplets are of paramount importance in drug targeting and therapeutic applications. However, conventional techniques for generating encapsulated magnetic microdroplets suffer from several challenges, including lack of monodispersity, inflexibility in core–shell combinations, and complex device architecture to achieve encapsulation. Herein, a facile magnet‐assisted framework to controllably wrap ferrofluid (FF) droplets inside polydimethylsiloxane (PDMS) floating on a water bath is developed. A permanent magnet placed at the bottom of a static glass cuvette pulls the ferrofluid droplet across the PDMS–water interface, which results in the wrapping of the FF droplet by a thin PDMS layer. The deformation of the FF–PDMS interface and the encapsulation of FF inside PDMS thereof is attributed to the interplay of magnetic force and force due to PDMS–water interfacial tension. Based on the experimental observations, three regimes are identified, namely, stable encapsulation, unstable encapsulation, and no encapsulation, which depends on the magnetic Bond number (Bom) and the thickness of the PDMS layer (δ). The versatility of the technique is demonstrated further by showing stable wrapping of multiple ferrofluid droplets inside the same encapsulated cargo and successful underwater manipulation of the encapsulated droplets, which finds relevance in the encapsulation and magnet‐assisted actuation of novel encapsulated materials.

Prediction and confirmation of a switch-like region within the N-terminal domain of hSIRT1

Many proteins display conformational changes resulting from allosteric regulation. Often only a few residues are crucial in conveying these structural and functional allosteric changes. These regions that undergo a significant change in structure upon receiving an input signal, such as molecular recognition, are defined as switch-like regions. Identifying these key residues within switch-like regions can help elucidate the mechanism of allosteric regulation and provide guidance for synthetic regulation. In this study, we combine a novel computational workflow with biochemical methods to identify a switch-like region in the N-terminal domain of human SIRT1 (hSIRT1), a lysine deacetylase that plays important roles in regulating cellular pathways. Based on primary sequence, computational methods predicted a region between residues 186–193 in hSIRT1 to exhibit switch-like behavior. Mutations were then introduced in this region and the resulting mutants were tested for allosteric reactions to resveratrol, a known hSIRT1 allosteric regulator. After fine-tuning the mutations based on comparison of known secondary structures, we were able to pinpoint M193 as the residue essential for allosteric regulation, likely by communicating the allosteric signal. Mutation of this residue maintained enzyme activity but abolished allosteric regulation by resveratrol. Our findings suggest a method to predict switch-like regions in allosterically regulated enzymes based on the primary sequence. If further validated, this could be an efficient way to identify key residues in enzymes for therapeutic drug targeting and other applications.

Advances in the Methods for the Synthesis of Carbon Dots and Their Emerging Applications.

Cutting-edge technologies are making inroads into new areas and this remarkable progress has been successfully influenced by the tiny level engineering of carbon dots technology, their synthesis advancement and impressive applications in the field of allied sciences. The advances of science and its conjugation with interdisciplinary fields emerged in carbon dots making, their controlled characterization and applications into faster, cheaper as well as more reliable products in various scientific domains. Thus, a new era in nanotechnology has developed into carbon dots technology. The understanding of the generation process, control on making processes and selected applications of carbon dots such as energy storage, environmental monitoring, catalysis, contaminates detections and complex environmental forensics, drug delivery, drug targeting and other biomedical applications, etc., are among the most promising applications of carbon dots and thus it is a prominent area of research today. In this regard, various types of carbon dot nanomaterials such as oxides, their composites and conjugations, etc., have been garnering significant attention due to their remarkable potential in this prominent area of energy, the environment and technology. Thus, the present paper highlights the role and importance of carbon dots, recent advancements in their synthesis methods, properties and emerging applications.

Identifying a switch‐like region within the N‐terminal domain of SIRT1

Many proteins display conformational changes upon allosteric regulation. Oftentimes a few key residues, deemed a switch or switch-like region, are crucial in conveying these structural and functional allosteric changes. Identifying these switch-like regions not only helps us understand the nature of the allosteric regulations, it also pinpoints a “hot spot” for highly efficient targeting by small molecules or other ligands. In this study, we combine computational and biochemical methods to identify a switch-like region in the N-terminal domain of SIRT1, a lysine deacylase that plays important roles in regulating cellular pathways. Using computational methods based on the primary sequence of SIRT1, a region between residues 186-193 was predicted to exhibit switch-like behavior. Mutations were then introduced in this region of SIRT1. The resulting mutant SIRT1 constructs were tested for allosteric reactions to resveratrol, a known SIRT1 allosteric regulator, using an enzyme-coupled continuous activity assay. Some mutants remained active but exhibited no change in enzyme activity upon the addition of resveratrol, suggesting that this region is indeed a switch-like region for allosteric regulations of SIRT1. Furthermore, we have been able to identify and narrow down the specific switch-like residues within this region. Our findings suggest a method to predict switch-like regions in allosterically regulated enzymes based solely on the primary sequence of proteins. If further validated, this could be an efficient way to identify key residues in enzymes for therapeutic drug targeting and other applications.

Microbial Fabricated Nanosystems: Applications in Drug Delivery and Targeting.

The emergence of nanosystems for different biomedical and drug delivery applications has drawn the attention of researchers worldwide. The likeness of microorganisms including bacteria, yeast, algae, fungi, and even viruses toward metals is well-known. Higher tolerance to toxic metals has opened up new avenues of designing microbial fabricated nanomaterials. Their synthesis, characterization and applications in bioremediation, biomineralization, and as a chelating agent has been well-documented and reviewed. Further, these materials, due to their ability to get functionalized, can also be used as theranostics i.e., both therapeutic as well as diagnostic agents in a single unit. Current article attempts to focus particularly on the application of such microbially derived nanoformulations as a drug delivery and targeting agent. Besides metal-based nanoparticles, there is enough evidence wherein nanoparticles have been formulated using only the organic component of microorganisms. Enzymes, peptides, polysaccharides, polyhydroxyalkanoate (PHA), poly-(amino acids) are amongst the most used biomolecules for guiding crystal growth and as a capping/reducing agent in the fabrication of nanoparticles. This has promulgated the idea of complete green chemistry biosynthesis of nano-organics that are most sought after in terms of their biocompatibility and bioavailability.

Spectral simulation to investigate the effects of nanoparticle diameter and nanolayer on the ferrofluid flow over a slippery rotating disk in the presence of low oscillating magnetic field

AbstractThis article explores the impacts of the solid–liquid interfacial layer and nanoparticle diameter on the unsteady ferrous‐water nanoliquid flow over a spinning disk. The existence of velocity slip is presumed on the disk. Additionally, the low oscillating magnetic field effect is included to extract the hydrothermal consequences of the problem. Shliomis theory has been presented to verbalize the foremost equations of the mentioned flow problem. The similarity transformation renders the dimensionless equations. Spectral quasilinearization technique along with the residual error profile is presented to resolve the converted equations. An adequate number of pictures and tables are portrayed to improve the parametric study of the problem. Several streamlines, isotherms, contour plots, and three‐dimensional figures are presented to disclose the hydrothermal integrity of the nanofluidic transport. Effective magnetization parameter produces 4.67% skin frictional increment. Heat transport declines for nanoparticle diameter but is enhanced for nanolayer conductivity ratio. The presence of an oscillating magnetic field always promotes heat transference as compared with the absence of the oscillating field. The nanolayer conductivity ratio conveys the highest 8.69% heat transport rate, whereas the magnetization factor provides the lowest, 1.79%. It has novel applications in magnetic drug targeting, hard disk scaling, magnetic resonance imaging, spin coating, lubrication, and so forth.

A Feasibility Study of In Vivo Control and Tracking of Microrobot Using Taxicab Geometry for Direct Drug Targeting.

In vivo direct drug targeting aims at delivering drug molecules loaded on microrobots to the diseased site using the shortest possible physiological routes, which potentially improves targeting efficiency and reduces systemic toxicity. It is thus essential to consider realistic in-body limitations for direct drug targeting applications. Here, we present a novel controller for microrobot maneuver by considering four key in vivo constraints: non-Euclidean structure of capillaries, irreversibility of blood flow, invisibility of microvasculature, and inaccuracy of microrobot tracking. We use the taxicab geometry of capillaries as the a priori knowledge for steering and tracking a microrobot in lattice-like vessels. Furthermore, we introduce a minimax repulsive boundary function to prevent the microrobot from getting too close to the boundaries imposed by the direction of blood flow. We also propose a novel Kalman filtering algorithm to reduce tracking error, while avoiding possible obstacles such as vessel walls without knowing their actual locations. The proposed control method consists of four modules, namely a model predictive control module for tumor targeting, a Kalman filtering module for microrobot tracking, a blind obstacle detection module, and a vessel structure estimation module. The interplay of these four modules offers successful maneuver and tracking of the microrobot while avoiding obstacles in a blind manner by utilizing the taxicab geometry of blood vessels. We present a comprehensive in silico simulation study to verify our designed controller.

Advancements in Polymer and Lipid-based Nanotherapeutics for Cancer Drug Targeting

Cancer is a global disease. It is the second leading cause of death worldwide, according to the health report. Approximately 70% of deaths from cancer occurs in low- and middle-income countries. According to the WHO, in 2015 8.8 million deaths were reported due to cancer worldwide. The conventional system of medicine was used since a long for the management of the disease, but it comes with the drawback of low safety, less efficacy and non-targeting of cancer cells. Nanotherapeutics has become the most exploited drug targeting system based on the safety and efficacy this system provides over the conventional system. This review summarizes an advanced design consideration in anticancer therapy, recent advancements in the nanocarrier-based advanced drug targeting, challenges and limitations related to nanoparticles-based therapy in cancer and its future perspective. The review also lists the on-going clinical trials in the last five years on nano-based therapy for different types of cancer. The data for this article was obtained by an extensive literature review of related published scientific contents from the WHO's website, PubMed, Scopus, Scielo, clinicaltrials.gov and other relevant scientific archiving services. The safety and efficacy that nanoparticles provide, and the current research strongly support their application in cancer drug targeting. However, their presence in the market is still limited. Nanotherapeutics in cancer drug targeting needs extensive research in association with pharmaceutical industries. Nano-targeting based therapies are the future of pharmaceutical designing for the diagnosis, management and prevention of different forms of cancer.

Transferrin-Mediated Glioblastoma Cell Targeting of Hexagonal Boron Nitrides

Hexagonal boron nitrides (hBNs) are promising nanomaterials with their high boron content, non-toxic nature in inactive form, high chemical stability, and mechanical strength. However, their hydrophobic nature limits their use in biomedical applications. Therefore, the hBNs have been functionalized with DSPE-PEG-NH2 to increase their colloidal stability and circulation time in bloodstream as well as to provide active sites on their surface for further functionalization with tumor-targeting agents. Then, further functionalization of the DSPE-PEG-hBNs with transferrin (TfR) was applied for selective targeting of transferrin receptors overexpressed by brain tumor cells. After that, the cellular interaction and biocompatibility of the structure was investigated on glioblastoma multiforme (U87MG) cancer cells. The cellular investigations showed that transferrin functionalization of the DSPE-PEG-hBNs increased their uptake by glioblastoma cancer cells and decreased cell viability due to the enhanced cellular internalization. Based on the data, the TfR-DSPE-PEG-hBNs are promising agents to evaluate them in drug carrying and targeting applications.