Drug Targeting Systems Research Articles

Liposomes and Their Therapeutic Applications in Enhancing Psoriasis and Breast Cancer Treatments.

Psoriasis and breast cancer are two examples of diseases where associated inflammatory pathways within the body's immune system are implicated. Psoriasis is a complex, chronic and incurable inflammatory skin disorder that is primarily recognized by thick, scaly plaques on the skin. The most noticeable pathophysiological effect of psoriasis is the abnormal proliferation of keratinocytes. Breast cancer is currently the most diagnosed cancer and the leading cause of cancer-related death among women globally. While treatments targeting the primary tumor have significantly improved, preventing metastasis with systemic treatments is less effective. Nanocarriers such as liposomes and lipid nanoparticles have emerged as promising drug delivery systems for drug targeting and specificity. Advances in technologies and drug combinations have emerged to develop more efficient lipid nanocarriers to include more than one drug in combinational therapy to enhance treatment outcomes and/or relief symptoms for better patients' quality of life. Although there are FDA-approved liposomes with anti-cancer drugs for breast cancer, there are still unmet clinical needs to reduce the side effects associated with those nanomedicines. Hence, combinational nano-therapy may eliminate some of the issues and challenges. Furthermore, there are no nanomedicines yet clinically available for psoriasis. Hence, this review will focus on liposomes encapsulated single and/or combinational therapy to augment treatment outcomes with an emphasis on the effectiveness of combinational therapy within liposomal-based nanoparticulate drug delivery systems to tackle psoriasis and breast cancer. This review will also include an overview of both diseases, challenges in delivering drug therapy and the roles of nanomedicines as well as psoriasis and breast cancer models used for testing therapeutic interventions to pave the way for effective in vivo testing prior to the clinical trials.

Review on Study of Nanoparticles in Brain Targeting for Treatment Of Alzheimer’s

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder, in which there is a progressive deterioration of intellectual and social functions, memory loss, personality changes and inability for self-care, and has become the fourth leading cause of death in developed countries. Pathogenesis of AD, there is a progressive deposition of β-amyloid (Aβ)- peptide in the hippocampal and cerebral cortical regions. This deposition is associated with the presence of neurofibrillary tangles (NFTs) and senile plaques. The senile plaques deposited between the neurons consist mainly protein β amyloid. Neurofibrillary tangles deposited inside the neurons fabricated from Tau protein. Diagnosing Alzheimer's requires careful medical evaluation thorough medical history, mental status testing, physical and neurological examination tests (such as blood tests and brain imaging), two classes of medications approved to treat AD. Cholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine, NMDA receptor antagonists: Memantine. The major goal in designing nanoparticles as a delivery system are to control particle size, surface property and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutic optimum rate and dose regimen of the agent to the CNS, but also the ability of the agent to access the relevant target site within the CNS. Many strategies have been developed to deliver the drug into brain by crossing the BBB: chemical delivery systems, magnetic drug targeting or drug carrier systems such as antibodies, liposomes or nanoparticles. Among those, nanoparticles have got a great concentration as the potential targeted drug delivery systems in the brain recently. Keywords: Alzheimer’s disease, β-amyloid, cholinesterase inhibitors, Curcumin nanoparticles.

Molecular docking, dynamics, and preclinical experimental studies identify Morin hydrate as a potent PPAR-γ and NRF-2 transcription factor agonist that mitigates colon inflammation

Introduction: Peroxisome proliferator-activated receptor gamma (PPAR-γ) plays a vital role in regulating intestine inflammation. PPAR-γ is highly expressed in the adipose tissue and the colon. The nuclear erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein1 (Keap1) system protects cells from oxidative stress and inflammation. Therefore, PPAR-γ and Nrf2 ligands offer a drug-targeting system that can be exploited to treat inflammatory bowel diseases (IBDs), especially ulcerative colitis. IBD prevalence is on the rise globally. Current mainstream therapies for IBD offer protection but with many side effects; therefore, up to 30% of IBD patients turn to alternate therapy using bioactive phytochemicals. Morin hydrate, a naturally occurring bioflavonoid in many fruits, stems, and leaves of the Moraceae family plant, possesses potent anti-inflammatory properties. The docking studies reveal that it is a potent activator of the PPAR-γ and Nrf2 transcription factors. Therefore, in this study, we investigated the role of morin hydrate modulating colon epithelial PPAR-γ transcription in colon inflammation. Aim: Therefore, this study aims to investigate morin hydrate’s anti-inflammatory properties using both in vivo and in vitro models of colon inflammation. Methodology: C57BL/6J black mice were administered 2% dextran sodium sulfate (DSS) morin hydrate administered at concentrations of 25 & 50mg/kg body for in vivo studies. The DAI, colon length, MPO, and histology changes were determined. Proinflammatory cytokines (IL-1β, IL-6, TNF-α, & IL17A) were measured using ELISA and mRNA using real-time PCR. PPAR-γ and Nrf2 expression and phosphoNF-κB/NF-κB expression were estimated. HT-29 cells were cultured in DMEM media and were stimulated using TNF-α (1ng/ml). Different concentrations of morin hydrate were treated to HT-29 cells to determine a safe dose range for further in vitro experiments by estimating cell toxicity assay. CXCL-1, IL-8, and mRNA levels were determined using real-time PCR after morin hydrate co-treatment. Morin hydrate effect on PPAR-γ and Nrf2 promoter activity was determined using full-length promoter transfection studies. Results: Morin treatment significantly ( p<0.01) decreased DAI, MPO level, and restored colon length dose-dependently in the treated group. Histological scoring for colonic inflammation was significantly ( p<0.001) improved upon morin treatment. Morin treatment also inhibited the proinflammatory cytokines (IL-1β, IL-6, TNF-α, & IL17A) significantly ( p<0.01) both at protein and mRNA levels. Morin significantly inhibited COX-2 and iNOS both at protein and mRNA levels and also decreased tissue nitrite levels. Morin also activated PPAR-γ protein expression NRF2 nuclear translocation and inhibited NF-κB expression in DSS-administered mice. Morin significantly decreased antioxidant surrogate markers superoxide dismutase (SOD) and catalase activity. Morin significantly ( p<0.01) decreased proinflammatory cytokine (CXCL-1 & IL-8) mRNA expression when HT-29 cells were challenged with TNF-α. Morin also increased PPAR-γ and Nrf2 promoter activity. Conclusion: Morin hydrate is a potent PPAR-γ and Nrf2 transcription factor activator that mitigates colon inflammation through its anti-inflammatory and antioxidant activities. This is supported from UAE University grant, fund number 12R006 and 12R169. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A nanobody-mediated drug system against largemouth bass virus delivered by bacterial nanocellulose in Micropterus salmoides

Diseases caused by pathogens severely hampered the development of aquaculture, especially largemouth bass virus (LMBV) has caused massive mortality and severe economic losses to the culture of largemouth bass (Micropterus salmoides). Considering the environmental hazards and human health, effective and environmentally friendly therapy strategy against LMBV is of vital importance and in pressing need. In the present study, a novel nanobody (NbE4) specific for LMBV was selected from a phage display nanobody library. Immunofluorescence and indirect ELISA showed that NbE4 could recognize LMBV virions and had strong binding capacity, but RT-qPCR evidenced that NBE4 did not render the virus uninfectious. Besides, antiviral drug ribavirin was used to construct a targeted drug system delivered by bacterial nanocellulose (BNC). RT-qPCR revealed that NbE4 could significantly enhance the antiviral activity of ribavirin in vitro and in vivo. The targeted drug delivery system (BNC-Ribavirin-NbE4, BRN) reduced the inflammatory response caused by LMBV infection and improved survival rate (BRN-L, 33.3 %; BRN-M, 46.7 %; BRN-H, 56.7 %)compared with control group (13.3 %), ribavirin group (RBV, 26.7 %) and BNC-ribavirin (BNC-R, 40.0 %), respectively. This research provided an effective antiviral strategy that improved the drug therapeutic effect and thus reduced the dosage.

A comprehensive study on the review of virosomes As a novel drug delivery system

Virosomes can be used as vaccines and vehicles for the cellular transport of various macromolecular molecules. The potential for drug delivery and targeting systems to be implemented using virosomes represents an exciting area of ​​research. Virosomes are biocompatible, biodegradable, nontoxic, and nonimmunogenic, so efforts have been made to utilize them as anti-inflammatory or adjuvant agents, as well as drug and organic delivery frameworks for therapeutic applications. The success of virosomal drug delivery depends on the strategy used to assemble and fuse typeable bioactive materials into virosomes. Potential innovations of virosomes could be used to transport peptides and nucleic acids or qualities and drugs such as antitoxins, anticancer agents, and steroids.

A fast Fibonacci wavelet-based numerical algorithm for the solution of HIV-infected cells model.

In this article, we present a novel approach under the Fibonacci wavelet and collocation technique which is computationally efficient to obtain the solution of the model of cells of HIV infection. A system of nonlinear ordinary differential equations represents this mathematical model. We have approximated unknown functions and their derivatives using the operational matrix of integration of Fibonacci wavelets to transform this model into a set of algebraic equations and then simplified using a suitable method. It is anticipated that the proposed approach would be more efficient and suitable for solving a variety of nonlinear ordinary and partial differential equations representing the model of medical, radiation, and surgical oncology, and drug targeting systems that occur in medical science and engineering. Tables and graphs are included to show how the suggested wavelet method provides enhanced accuracy for a wide range of problems. Relative data and computations are performed over MATLAB software.

The effects of epirubicin-loaded Boc-L-Diphenylalanine peptide nanoparticles on cytotoxicity, genotoxicity, oxidative stress, and apoptosis in non-small cell lung cancer cells.

Peptides, which are important components of the human body, appear in different chemistry applications. Perhaps the most important of these applications is the use of these structures in drug delivery systems due to their biocompatibility properties. Diphenylalanine (FF) peptide-based systems, which are part of the ß-amyloid polypeptide sequence and are known as the smallest dipeptide group, are particularly preferred due to their biocompatible nature, thermal stability, high ionic strength in water in new targeted drug systems. Epirubicin, the epimer of doxorubicin, is utilized in treating lung cancer. The side effects and the applied doses of epirubicin are being tried to be reduced. Therefore, in this study, epirubicin-loaded tert-butyloxycarbonyl protected diphenylalanine (Boc)-FF particles were synthesized and characterized and the effects of these peptides on cytotoxicity, genotoxicity, oxidative stress and apoptosis on non-small cell lung cancer cells (NSCLC) (A549) were evaluated. According to the results of the study, it was determined that epirubicin-loaded Boc-FF dipeptides significantly reduced the viability, oxidative stress, and increased DNA damage and apoptosis in the cells. The study suggests that epirubicin-loaded Boc-FF particles can be used as an alternative drug carrier for NSCLC treatment due to their physiological, chemical, and biological activity.

Recent Advancements in Biomimetic Drug Delivery System of Single- Chain Fatty Acids as Ufasomes and Ufosomes: A Comprehensive Review

Abstract: The current review is focused on many carrier systems and technologies that have recently been explored for achieving controlled drug release, promoting therapeutic potential, and selectivity. Among various carrier systems, the vesicular drug delivery system is the highly effective method of delivering medication to the infection site resulting in minimal drug toxicity and adverse effects. Various research studies have been conducted to reduce drug loss and degradation, prevent unwanted side effects, improve drug bioavailability, and retain the fraction of drug in the necessary region. To achieve these goals novel vesicular drug delivery and vesicular drug targeting systems, such as ufasomes and ufosomes, are currently under research. They are highly ordered self-assembled novel vesicular drug delivery systems formed from disordered building blocks into highly ordered systems by specific inter-block mutual interactions. These two carrier systems are separately being studied for their efficacy to improve the effectiveness of various drugs. In this perspective, we summarized the basic concept and recent studies on ufasomes and ufosomes for drug delivery along with pertinent investigations in the present review. The vesicular systems discussed in this article are given chronologically, from existing systems to advanced fatty acid vesicles. Drug design and development using ufasome and ufosome vesicular systems have added a new dimension to the treatment of disease conditions by circumventing penetration limiting obstacles and therefore increasing efficacy.

A prediction model for magnetic particle imaging–based magnetic hyperthermia applied to a brain tumor model

Background and objectiveBrain tumor is a global health concern at the moment. Thus far, the only treatments available are radiotherapy and chemotherapy, which have several drawbacks such as low survival rates and low treatment efficacy due to obstruction of the blood-brain barrier. Magnetic hyperthermia (MH) using magnetic nanoparticles (MNPs) is a promising non-invasive approach that has the potential for tumor treatment in deep tissues. Due to the limitations of the current drug-targeting systems, only a small proportion of the injected MNPs can be delivered to the desired area and the rest are distributed throughout the body. Thus, the application of conventional MH can lead to damage to healthy tissues. MethodsMagnetic particle imaging (MPI)-guided treatment platform for MH is an emerging approach that can be used for spatial localization of MH to arbitrarily selected regions by using the MPI magnetic field gradient. Although the feasibility of this method has been demonstrated experimentally, a multidimensional prediction model, which is of crucial importance for treatment planning, has not yet been developed. Hence, in this study, the time dependent magnetization equation derived by Martsenyuk, Raikher, and Shliomis (which is a macroscopic equation of motion derived from the Fokker-Planck equation for particles with Brownian relaxation mechanism) and the bio-heat equations have been used to develop and investigate a three-dimensional model that predicts specific loss power (SLP), its spatio-thermal resolution (temperature distribution), and the fraction of damage in brain tumors. ResultsBased on the simulation results, the spatio-thermal resolution in focused heating depends, in a complex manner, on several parameters ranging from MNPs properties to magnetic fields characteristics, and coils configuration. However, to achieve a high performance in focused heating, the direction and the relative amplitude of the AC magnetic heating field with respect to the magnetic field gradient are among the most important parameters that need to be optimized. The temperature distribution and fraction of the damage in a simple brain model bearing a tumor were also obtained. ConclusionsThe complexity in the relationship between the MNPs properties and fields parameter imposes a trade-off between the heating efficiency of MNPs and the accuracy (resolution) of the focused heating. Therefore, the system configuration and field parameters should be chosen carefully for each specific treatment scenario. In future, the results of the model are expected to lead to the development of an MPI-guided MH treatment platform for brain tumor therapy. However, for more accurate quantitative results in such a platform, a magnetization dynamics model that takes into account coupled Néel-Brownian relaxation mechanism in the MNPs should be developed.

Targeted magnetochemotherapy modified by 5-Fu-loaded thermally on/off switching nanoheaters for the eradication of CT26 murine colon cancer by inducing apoptotic and autophagic cell death

Despite significant breakthroughs in diagnosis and treatment of colorectal cancer (CRC), the extent of morbidity and mortality secondary to CRC is still concerning. In this study, we evaluated the efficacy of our new tumor-selective nanoplatforms at induction of apoptosis and autophagy, which was tested using active 5-fluorouracil (5-Fu)-based targeting of tumor cells in a BALB/c murine model of CRC combined with magnetic thermal therapy. Nanoparticles were synthesized and characterized by zeta sizer, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The cytotoxicity and tissue uptake of 5-Fu-loaded folic acid (Fa)-modified magnetic nanoparticles (5-Fu/MNPs-Fa) was assessed using MTT, ICP-OES, and HPLC. The rate of apoptosis and autophagy, as two major indicators of antitumor activity, was measured based on protein expression of Bax, Bcl2, Caspase 3, mTOR, P-mTOR, Beclin-1, and LC3B in CT-26 murine CRC, along with tumor volume and survival time. The spherical 5-Fu/MNPs-Fa exhibited sustained thermal on/off switching drug release and higher therapeutic index compared to free 5-Fu. Our de novo synthetized magnetic nanoheaters successfully delivered the therapeutic agent to the tumor site, enhanced the conversion of radio frequency energy to heat in tumor cells, exhibited higher antitumor efficiency based on Bax/Bcl2 ratio and overexpression of Beclin-1 and LC3B, increased the survival time, and decreased the tumor volume (P < 0.05). Our findings indicated that magnetochemotherapy (MHC) was substantially more effective than hyperthermia and/or chemotherapy alone. From a translational standpoint, the 5-Fu/MNPs-Fa would be a promising candidate sustained drug targeting system that could improve cancer cell therapy via inducing apoptosis and autophagy.Graphical

Significance of Hydrophobic Polymer in Novel Drug Delivery System

Polymers, due to their diverse topology and chemistry, account for a significant portion of the materials used in controlled release formulations and drug-targeting systems. They have played an integral role in the advancement of drug delivery technology by providing controlled release of therapeutic agents in constant doses over long periods, cyclic dosage, and tunable release of both hydrophilic and hydrophobic drugs. Eudragit is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives. Eudragits are amorphous polymers having glass transition temperatures between 9 to &gt; 150o C. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH &gt; 6 and is used for enteric coating, while Eudragit S, soluble at pH &gt; 7 is used for colon targeting. In this review, the physicochemical characteristics and applications of different grades of Eudragit in colon-specific/enteric-coated/ sustained release drug delivery and taste masking have been addressed.

Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer

Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemotherapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocyanine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photothermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near-infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.

Ex vivo model for the measurement of intraocular pressure and force of injection during the administration of hollow microneedles in porcine sclera

AbstractPurpose: The current gold standard treatment option for posterior segment diseases such as age‐related macular degeneration is the delivery of drug into the vitreous cavity by intravitreal injection. This method is, however, associated with several issues including low patient compliance and the risk of adverse effects [1]. Microneedles (MNs), designed to deliver their payload into the sclera, offer a minimally invasive means of providing localized drug delivery to the eye, providing a potentially more patient‐friendly alternative. MNs for ocular drug delivery have gained significant interest in recent years; however, for clinical acceptability, safe values for parameters such the injection force and changes in intraocular pressure (IOP) are critical. This work investigated the effects that changing MN design parameters (e.g., bevel angle, needle length and needle gauge) had on both the force of penetration (FoP) and depth of penetration (DoP) achieved in ex vivo porcine sclera at clinically relevant locations. The model used a pressure transducer to allow for real‐time monitoring of IOP over the injection procedure.Methods: Stainless steel hollow microneedles (ssHMNs) were fabricated from conventional hypodermic needles, with a range of bevel angles (30–75°) cut in triplicate using Wire Electrical Discharge Machining. Needle heights were adjusted as required using 3D‐printed adapters. To assess FoP and DoP, ssHMNs were inserted into ex vivo porcine sclera with images being captured using optical coherence topography. IOP changes during the injection procedure were monitored in real‐time using a pressure transducer.Results: ssHMNs were shown to partially penetrate the ex vivo porcine sclera. Average values obtained for FoP and DoP were shown to be dependent on sclera location. Peak IOP values were observed upon scleral penetration, with these being lower with smaller needle sizes. Similarly, average FoP values were found to decrease for higher gauge needles and smaller bevel angles.Conclusions: This work demonstrates the effects of changing design parameters of ssHMNs on the FoP and DOP achieved in ex vivo porcine sclera, as well as changes in IOP.Reference1. “Stimuli sensitive ocular drug delivery systems,” in Drug Targeting and Stimuli Sensitive Drug Delivery Systems, 2018, pp. 211–270.

Utilization of novel lectin-conjugated Au nanoparticles as Thomsen-Friedenreich onco-antigen target for in vitro cytotoxicity and apoptosis induction in leukemic cell line

Leukemia is a tumor of blood-forming tissues including bone marrow and lymphatic nodes, which comprise biologically distinct subgroups. In the present study, Au NPs-PEG-Lectin was prepared as a drug targeting system for potential Thomsen-Friedenreich antigen (TF-Ag) presented on the surface of leukemic cells to induce cytotoxicity. Gold nanoparticles were prepared using citrate reduction method and conjugated with lectin via SH-PEG-COOH. The conjugate was characterized using UV/Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Zeta potential, and Scanning electron microscopy (SEM) with subsequent applications for cytotoxicity, cell cycle analysis, and apoptosis. Immunophenotypically blood samples from patients with acute lymphoblastic leukemia (ALL) were positively expressed CD45, CD95 dim expression, and low CD176 (TF-Ag) expression. Samples of acute myeloid leukemia (AML) confirmed the expression of all markers. Au NPs-PEG-Lectin conjugate showed an average size of 35.82 nm with zeta potential of −27.33 with accelerated lectin release from the conjugate at acidic pH. Au NPs-PEG-Lectin demonstrated the highest and most significant cytotoxic activity against HL-60 and K562 with IC50 of 132.5 and 314.8 μg mL−1, respectively. Flow cytometric analysis revealed induction of HL-60 cell apoptosis upon conjugate treatment in a dose-dependent pattern up to 51.03 % with no sign of necrosis with cell cycle arrest at G0/G1 phase. HL-60 cells treated with Au NPs-PEG-Lectin exhibited inter-nucleosomal DNA fragmentation. Morphologically, Phospho-Histone/BrdU dual staining indicated that Au NPs-PEG-Lectin initiated HL-60 arrest at G0/G1 phase. Taken together, molecular docking verified the possible interaction between lectin amino acids and different hydroxy groups within TF-Ag forming hydrogen bonds.

Safety assessment of different unloaded polymeric nanocapsules in Caenorhabditis elegans

Nano-sized drug delivery systems have been the subject of intense research in recent years because polymeric materials allow the absorption and release of active substances in a controlled manner. Despite the benefits, the safety of nanoparticulate systems is an aspect to be understood, particularly in vivo systems. Caenorhabditis elegans is a very useful alternative model for nanotoxicology and has been recently applied in this field. The aim of this study was to evaluate toxicological endpoints in C. elegans exposed to nanocapsules (NC) prepared with different coatings: polysorbate 80 (NCP80); polyethylene glycol (NCPEG), Eudragit® RS 100 (NCEUD) and chitosan (NCCS). Nanocapsules were prepared by nanoprecipitation method and showed acceptable physico-chemical characterization. Polyethylene glycol nanocapsules and chitosan nanocapsules increased worms lethality in a dose-dependent manner in acute exposure; polysorbate 80 nanocapsules, polyethylene glycol nanocpsules and chitonan nanocapsules also increased lethality following chronic exposure. Chitosan nanocapsules were the most toxic in all exposures, demonstrating toxicity even at low concentrations. Reproduction and body length were not affected by any of the nanocapsules exposures. The expression of superoxide dismutase showed that polysorbate 80 nanocapsules at the highest concentration slightly increased SOD-3::GFP expression. On the other hand, chitosan nanocapsules exposure blunted SOD-3 expression. This work demonstrates the toxicological differences between nanocapsule produced with different coatings and indicates higher safety for the use of eugragit nanocapsule in new formulations for future drug delivery and targeting systems.

Externally Triggered Drug Delivery Techniques Using Micro and Nanoparticles

The need for sustained and better-controlled drug administration has led to development of novel drug delivery systems. The concentration of a drug in blood at any given time depends on the prescribed routine of drug intake. Conventional methods of drug intake do not always maintain the required consistent drug concentration. Controlled drug release mechanisms can help in maintaining drug dosage levels while optimizing therapeutic effects. Microparticles and nanoparticles, initially developed as carriers for vaccines and anticancer drugs, are being used in drug delivery systems for drug targeting, improved release profile and efficiency. The drugs can be encapsulated inside the particles, suspended in or with them. However, release of the drug depends on the type of techniques used to trigger drug delivery. This review outlines the major techniques used for drug delivery applications based on external triggering mechanisms while utilising micro and/or nanoparticles. These techniques include ultrasound, light, radiofrequency, electric and magnetic field exposures. Most of these techniques have largely remained in vitro owing to challenges concerning safety due to exposure levels and penetration of external signals due to human physiology. Considering these aspects of the challenge, microwave based external triggering can be a prospective technology for drug delivery using micro and nanoparticles.

Two-phase bio-nanofluid flow through a bifurcated artery with magnetic field interaction

A modified multiphase flow model is applied for a better understanding of bio-nanofluid (blood containing 4% (w/v) Fe3O4 nanoparticles) flow regimes through a real bifurcated artery. The magnetic field with distinct current intensities (I = 0 – 300 A) was employed to induce the flow features when the wire's source is placed nearby the junction of the asymmetrical branched artery during numerical computation. The finite volume method was used to solve the coupled hemodynamics model. Results show that the pressure, and vorticity profiles increased and fallen gradually with the existence of the magnetic source and further obtained the maximum pressure for the strong current intensity (I = 300 A). The fluctuating vorticity distributions are found along the inner and outer vessel wall as well as the predicted lines created within the simulated domain for the increase of current intensity. The velocity outlines variates steadily, and the local peak velocities are obtained with the increase of the magnetic force. With the increment of the current intensity upto I = 300 A, the flow rate rises progressively for the asymmetric branched vessel, and the opposite scenario is found for the root vessel. The temperature profiles decrease steadily with the increment of the applied current intensity. With the manifestation of the magnetic source, the irregular flow behaviours are found within the asymmetrical bifurcated artery. This modeling investigation could be beneficial for the emergent therapy plan of ample vascular diseases as the magnetic drug targeting system.

Functionalization of β-cyclodextrin with a urea-based PSMA ligand and preliminary studies on targeting prostate cancer cells

Targeted delivery of drugs into specific cancer cells is an effective way to enhance the efficacy and minimize the side effects of therapy. Prostate malignant cells overexpress the prostate-specific membrane antigen (PSMA), a membrane protein that may be a valid target for selective drug administration. To target prostate cancer cells, a β-cyclodextrin perfunctionalised with dipeptide-like urea arms, a well-established mimic of a selective ligand against PSMA, is herein reported, to develop a multivalent drug delivery and targeting system. Firstly, fluorescein was used to validate the system on cells that express high levels of PSMA (prostate tumoral cells, LNCap) or very low levels of PSMA (non-tumoral cells, Hek293T). Then, the antineoplastic agent doxorubicin complexed with β-cyclodextrin functionalized with PSMA-like ligand takes less time to induce cytotoxicity on LNCap cells compared to doxorubicin alone. This might represent a promising drug-delivery approach to selectively target prostate cancer cells.

Dynamics of Williamson Ferro-nanofluid due to bioconvection in the portfolio of magnetic dipole and activation energy over a stretching sheet

The significance of the present work is that it is very useful in different fields of bio-engineering and engineering including magnetic drug targeting systems, magnetic hyperthymia, directing of magnetic drugs and etc. This paper explored the mechanical features of the magnetic dipole, activation energy and chemical reaction over the MHD flow of two-dimensional non-Newtonian Williamson Ferro-nanofluid under the stretched surface. The main aim of using the magnetic dipole effect in this problem is to control the momentum and thermal boundary layer thickness with the combining impact of nanofluid. As a result, the current approach is extremely valuable for controlling the thickness of thermal and momentum boundary layers. The thermal radiation and heat source/sink impacts are included in the heat equation for the calculation of heat transmission phenomena. The role of the gyrotactic microorganisms is discussed in the present analysis. The influence of Brownian motion and thermophoresis are also examined. The present mechanical system is formulated in the form of the higher-order PDEs and these nonlinear PDEs are relocated into the nonlinear higher-order ODEs by using the suitable similarity transformations. In the methodology section, for the solution of these highly nonlinear ODEs, the homotopic analysis scheme is employed. The effects of distinct flow parameters on the velocity, temperature, concentration and motile gyrotactic microorganism of the Williamson nanoliquid are scrutinized and discoursed in a graphical form. The following are some key outcomes from this analysis, it is predicted that the speed of the nanoliquid particles is lesser for nanoparticle volume fraction. Also, it is examined that the activation energy boosted the nanofluid concentration. Computation for streamline is performed in the present study.

On the entropy optimization of hemodynamic peristaltic pumping of a nanofluid with geometry effects

Recent studies in nanoscience and technology have emphasized the significance of the nanofluid in biomedical engineering like drug targeting systems, biotherapy and treatment of cancer. The present article is opted to analyze the impact of copper and diamond nanoparticles on peristaltic pumping of couple stress nanofluid regulated by the electro-magneto-hydrodynamic mechanism in a vertical microchannel. The influences of thermal radiation, convective and slip boundary conditions are also considered. In this study, the blood is treated as a coupled stress fluid, nanoparticles with four types of shapes (sphere, platelet, blade and cylinder) have been taken into account. The lubrication approach is carried out for mathematical modeling. The resulting non-linear system of equations has been solved analytically. The impacts of pertinent parameters on shear stress, velocity, temperature, heat transfer rate and entropy generation are shown through pictorial representations. From the current study, it is observed that the couple stress parameter reduces velocity and enhances pressure gradient and shear stress of nanofluid. The entropy generation enhances with sphere-shaped nanoparticles. Magnetic field strength reduces the bolus size. The thermal radiation diminishes the rate of heat transfer and nanofluid temperature increases with heat generation effects.