Targeted Drug Delivery Systems Research Articles

Research Progress of Drug Delivery Systems Targeting the Kidneys

Research Progress of Drug Delivery Systems Targeting the Kidneys

Advances in Microfluidic-based Core@Shell Nanoparticles Fabrication for Cancer Applications.

Current research in cancer therapy focuses on personalized therapies, through nanotechnology-based targeted drug delivery systems. Particularly, controlled drug release with core-shell nanoparticles can be designed to safely transport various active agents, optimizing delivery to specific organs and tumors, minimizing side effects. The use of microfluidics in this field has stood out against conventional methods by allowing precise control over parameters like size, structure, composition, and mechanical/biological properties of nanoscale carriers. This review compiles applications of microfluidics in the production of core-shell nanoparticles for cancer therapy, discussing the versatility inherent in various microchannel and/or micromixer setups and showcasing how these setups can be utilized individually or in combination, as well as how this technology allowed the development of new advances in more efficient and controlled fabrication of core-shell nanoformulations. Recent biological studies have achieved an effective, safe and controlled delivery of otherwise unreliable encapsulants such as siRNA, pDNA, and cisplatin as a result of precisely tuned fabrication of nanocarriers, showing that this technology is paving the way for innovative strategies in cancer therapy nanofabrication, characterized by continuous production and high reproducibility. Finally, this review analyses the technical, biological, and technological limitations that currently prevent this technology from becoming the standard. This article is protected by copyright. All rights reserved.

Shape Matters: Impact of Mesoporous Silica Nanoparticle Morphology on Anti-Tumor Efficacy

A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2 = 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2 = 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2 = 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.

Dual targeting total saponins of Pulsatilla of natural polymer crosslinked gel beads with multiple therapeutic effects for ulcerative colitis

Oral colon targeted drug delivery system (OCTDDS) is desirable for the treatment of ulcerative colitis (UC). In this study, we designed a partially oxidized sodium alginate-chitosan crosslinked microsphere for UC treatment. Dissipative particle dynamics (DPD) was used to study the formation and enzyme response of gel beads from a molecular perspective. The formed gel beads have a narrow particle size distribution, a compact structure, low cytotoxicity and great colon targeting in vitro and in vivo. Animal experiments demonstrated that gel beads promoted colonic epithelial barrier integrity, decreased the level of pro-inflammatory factors, accelerated the recovery of intestinal microbial homeostasis in UC rats and restored the intestinal metabolic disorders. In conclusion, our gel bead is a promising approach for the treatment of UC and significant for the researches on the pathogenesis and treatment mechanism of UC.

Chitosan mediated smart Photodynamic therapy based novel drug delivery systems- a futuristic view

In order to improve the pharmacological and therapeutic properties of drugs, researchers have attempted numerous novel approaches, such as stimuli-responsive systems, and targeted drug delivery systems. These systems can be attempted by nano-based drug delivery systems involving biocompatible polymers. One among which is chitosan, a linear polysaccharide, a promising potential polymer that gained interest in delivering challenging drugs. Chitosan can encapsulate and release the drugs in a controlled/sustained manner. Chitosan can be used to develop a variety of drug delivery carriers, including films, gels, nanoparticles, nanodispersions, nanomicelles, and patches. In this regimen, minimally invasive photodynamic therapy has recently gained much interest in treating vascular diseases, including cancer, ocular diseases, microbial infections, skin disorders, etc. Photodynamic therapy utilizes light excited at a specific wavelength, eliciting singlet oxygen production. Self-lighting photodynamic therapy and combination-based photodynamic therapy also offer synergistic effects. Photodynamic therapy is more selective and specific, which may offer treatment for deep-seated diseased tissues compared to conventional therapeutic modalities. Light-activated novel drug delivery formulations have been reported using various biocompatible polymers, including chitosan. Chitosan offers its effectiveness as mucoadhesiveness, tissue penetrability, antioxidant, antimicrobial properties, supports in singlet oxygen generation, and shown its benefits in photodynamic therapy. Therefore, this review presents numerous applications of chitosan-based light-activated drug delivery systems with particular emphasis on their patents and clinical trials. The literature has been collected and compiled using various search resources such as Science Direct, J-Gate, Google Scholar, PubMed, and research data.

Zwitterionic targeting nanodrugs prepared from poly(propyleneimine) dendrimers for enhanced anti-tumor therapy

Development of targeting and high drug loading drug delivery system has been gaining great interest. Zwitterionic modification of the terminal amine groups on G2 poly(propyleneimine) (G2 PPI) dendrimers was achieved via the thiol-ene click reaction, followed by the introduction of the anti-cancer drug paclitaxel and targeting peptides c(RGDfC), then the micelles were formed through self-assembly behavior, subsequently doxorubicin was encapsulated internally, finally the targeting drug-loaded micelles PPIMPRC-DOX were synthesized. The PPIMPRC-DOX micelles were irregular spherical with good monodispersity. The average particle size from TEM image was 63.05nm and the hydrodynamic size was 93.1nm, both of which were relatively uniform. The critical micelle concentration was 48.52μg/mL, the total drug loading efficiency was 32.45%. In vitro release experiments revealed that within the mildly acidic environment of tumors, PPIMPRC-DOX micelles exhibited enhanced release efficiency and increased accumulation of DOX. The anti-nonspecific protein adsorption experiment proved that the interaction between the PPIMPRC-DOX micelles and fibrinogen was very weak, and they had good anti-nonspecific protein adsorption ability. The cytotoxicity assessments using the MTT assay on HeLa cells and A549 cells revealed obvious cytotoxic effects of PPIMPRC-DOX micelles on both cells. Hence, the utilization of zwitterionic G2 PPI dendrimers in constructing PPIMPRC-DOX micelles holds promise as a prospective nanodrug delivery system.

Mitochondria Targeted Drug Delivery System Overcoming Drug Resistance in Intrahepatic Cholangiocarcinoma by Reprogramming Lipid Metabolism

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.

Brain Targeted Drug Delivery System for Microglial Diseases: Recent Developments in Neuroinflammation and Neurodegeneration

Development, Evaluation, and Molecular Dynamics Study of Ampicillin-Loaded Chitosan-Hyaluronic Acid Films as a Drug Delivery System.

Periodontitis is an inflammatory periodontal disease defined by the progressive loss of tissues surrounding the tooth. Ampicillin is an antibiotic for managing and treating specific bacterial infections, including periodontitis. Periodontal pockets occur due to periodontal disease progression and act as a natural reservoir that is easily reachable for the insertion of a delivery system, and the amount of drug to be released has a major role in the efficiency of treatment of the disease. Polyelectrolyte complexes (PECs), particularly those based on chitosan and hyaluronic acid combinations, offer a promising avenue to overcome the challenges associated with drug delivery. These complexes are both biodegradable and biocompatible, making them an optimal choice for enabling targeted drug delivery. This study centers on developing and assessing the structure and dynamic attributes of a drug-PEC system encompassing ampicillin and chitosan-hyaluronic acid components, which represents a targeted drug delivery system to better alleviate the periodontitis. To achieve this goal, we conducted experiments including weight and drug content uniformity, swelling ındex, drug release %, FT-IR and SEM analyses, and atomistic molecular dynamics simulations on the drug PECs loaded with ampicillin with varying amounts of hyaluronic acid. All simulations and the experimental analysis suggested that increased HA amount resulted in an increase in drug release % and swelling index. The simulation outcomes provide insights into the nature of the drug and PEC interactions alongside transport properties such as drug diffusion coefficients. These coefficients offer valuable insights into the molecular behavior of ampicillin-PEC drug delivery systems, particularly in the context of their application in periodontitis treatment.

Decomposition of Luminescent Hydroxyapatite Scaffolds in Simulated Body Fluid.

We present a luminescence study investigating the dissolution of rare-earth-doped hydroxyapatite scaffolds in simulated body fluid (SBF), aiming to assess the luminescence stability of Tb-, Ce-, and Eu-doped scaffolds over time. Our findings reveal a consistent decrease in luminescence emission intensity across all samples over a four-week period in which the scaffolds were immersed in the SBF. In addition, energy-dispersive spectroscopy confirms a decrease in rare-earth ion concentration in the scaffolds with respect to time, whereas fluorescence spectroscopy shows the presence of rare-earth ions in the SBF, indicating the partial dissolution of the scaffolds over time. The use of rare-earth ions as luminescence markers provides insights into the mechanisms of apatite formation in hydroxyapatites. Thus, these scaffolds may find wider use in regenerative medicine, particularly in targeted drug delivery systems, where their luminescent properties have the potential to noninvasively track drug release.

Titania NPs: A Review of Their Versatile Roles in Medicine and Synthesis Methods

Abstract: In this study, we investigate the various applications of titania in the medical field. Titania, renowned for its biocompatibility and distinctive properties, plays a significant role in pharmaceutical formulations. It is vital in coating tablets and capsules, improving drug stability and appearance. Additionally, titania nanoparticles (NPs) facilitate targeted drug delivery systems, enhancing therapeutic outcomes. Furthermore, we explore the promising prospects of titania-based photocatalysts in photodynamic therapy, highlighting their potential to transform cancer treatment and combat microbial infections. This comprehensive examination underscores the diverse and promising opportunities in which titania significantly advances medicine.

Mixed bioconvection of nanofluid of oxytactic bacteria through a porous cavity with inlet and outlet under periodic magnetic field using artificial intelligence based on LightGBM algorithm

The comprehension of microorganisms’ responses to magnetic field and fluid motion offers potential for the advancement of targeted drug delivery systems or medical interventions reliant on biological fluids. In this paper, the mixed bioconvection flow of nanofluid of oxytactic bacteria has been investigated through a porous cavity with inlet and outlet ports under the impact of periodic magnetic field. All the walls of the cavity are fixed at the constant high temperature. The proposed problem has been modeled first and then simulated using the finite element method. The computed computational fluid dynamics results have been analyzed for the several important controlling parameters. It is observed that there is at least 65% increment on heat transfer between the lowest and highest Peclet numbers. Further, regression analysis was conducted using the LightGBM algorithm. Careful parameter tuning was performed to avoid overfitting, ensuring that the model did not memorize the training data. According to the R2 values used for regression analysis, in the 18 datasets used for the performance metric comparison of the artificial intelligence model, a total of 18 targets were tried to be predicted for different Richardson number (0.1, 1, and 10) and Lewis Number (0.1, 1, and 10) values for each motile microorganisms, temperature and oxygen concentration values specified in the datasets, and a minimum accuracy of 95% and a maximum accuracy of 98% were obtained. These findings demonstrate the capability of the LightGBM algorithm to accurately predict the target variable within a high range of accuracy for the given datasets.

Self-Assembly of Peptides as an Alluring Approach toward Cancer Treatment and Imaging.

Cancer is a severe threat to humans, as it is the second leading cause of death after cardiovascular diseases and still poses the biggest challenge in the world of medicine. Due to its higher mortality rates and resistance, it requires a more focused and productive approach to provide the solution for it. Many therapies promising to deliver favorable results, such as chemotherapy and radiotherapy, have come up with more negatives than positives. Therefore, a new class of medicinal solutions and a more targeted approach is of the essence. This review highlights the alluring properties, configurations, and self-assembly of peptide molecules which benefit the traditional approach toward cancer therapy while sparing the healthy cells in the process. As targeted drug delivery systems, self-assembled peptides offer a wide spectrum of conjugation, biocompatibility, degradability-controlled responsiveness, and biomedical applications, including cancer treatment and cancer imaging.

Nanogels as Drug Delivery Carrier: A Narrative Review on Formulation Techniques, Characterization, Applications, and Patents.

Under the umbrella of targeted drug delivery systems, several techniques are unleashed in the market that allow a drug or other pharmacologically active material to be delivered to the target cell to treat a condition or health problem. The improvement of the pharmaceutical delivery systems' effectiveness, safety, and stability is accomplished through the Formulation of the nano-gel-based delivery system. Nanogels are aqueous dispersions of submicronsized, three-dimensional, strongly cross-linked networks of hydrophilic polymers that are inflated by water. Through a variety of delivery routes, such as oral, pulmonary, nasal, parenteral, and intraocular, an active pharmaceutical agent or therapeutic agent with a high or low molecular weight can be easily encapsulated into nanogels. Nanogels have been researched as drug delivery systems due to their beneficial qualities, such as biocompatibility, high stability, flexible particle size, drug loading capacity, and potential surface modification for active targeting by attaching ligands that recognize cognate receptors on target cells or tissues. By responding to internal or external stimuli, including pH, temperature, light, and redox, nano gels can be made to be stimulus-responsive, allowing for regulated drug release. Thus, in the fact of said characteristics' of nano gels, this review manuscript aims to provide an overview of characterization, evaluation, formulation technique, recent applications, and patents of nano gels.

Light‐Driven Multi‐Core/Shell Microdroplets as a Targeted Drug Delivery System

AbstractTargeted drug delivery system (DDS) holds exciting prospects in biomedical clinical research and drug development. However, it faces a significant challenge in achieving stable and safe targeted transportation without drug leakage while obtaining precise and controllable drug dosing with a high drug utilization rate and low side effects. Herein, an optical tweezers‐based light‐driven technique is proposed to transport and construct multi‐core/shell microdroplets enveloping drug carriers and target cells as a novel, safe, and efficient targeted DDS. Drug‐loaded microdroplets with core/shell structures are first fabricated by a new and simple injection extrusion method and then it is transported to a target cell by a dynamic optical trap with a low optical power, which ensures no drug leakage, exogenous materials, and biothermal damage are introduced during the drug delivery process. Next, precise drug dosing is realized by pushing the target cell into the drug‐loaded microdroplet under the actions of optical forces, which constructs a multi‐core/shell microdroplet structure with a pure drug environment to improve the drug action efficiency. Moreover, quantitative drug dosing with a high drug utilization rate can also achieved by controlling the sizes/number of drug droplets inside the microdroplets. This light‐driven DDS is of great interest to frontier medical research and disease treatment fields.

Aptamers for the Delivery of Plant-Based Compounds: A Review.

Natural compounds have a high potential for the treatment of various conditions, including infections, inflammatory diseases, and cancer. However, they usually present poor pharmacokinetics, low specificity, and even toxicity, which limits their use. Therefore, targeted drug delivery systems, typically composed of a carrier and a targeting ligand, can enhance natural product selectivity and effectiveness. Notably, aptamers-short RNA or single-stranded DNA molecules-have gained attention as promising ligands in targeted drug delivery since they are simple to synthesize and modify, and they present high tissue permeability, stability, and a wide array of available targets. The combination of natural products, namely plant-based compounds, with a drug delivery system utilizing aptamers as targeting agents represents an emerging strategy that has the potential to broaden its applications. This review discusses the potential of aptamers as targeting agents in the delivery of natural compounds, as well as new trends and developments in their utilization in the field of medicine.

Targeted Drug Delivery through the Synthesis of Magnetite Nanoparticle by Co-Precipitation Method and Creating a Silica Coating on it

Billions of dollars are spent annually in the world to treat and investigate problems caused by drug side effects. According to the estimation of health researchers, a huge part of people who take medicine suffer from complications caused by it. In this way, the necessity of using a targeted system in order to deliver medicine to the targeted place without damaging healthy tissues is felt more than before. In recent years, targeted drug delivery systems based on nanoparticles have received much attention. In the same direction, in this research, co-precipitation method was used to prepare magnetic nanoparticles using iron(|) and iron(||) oxides, and further, according to the synthesis steps of magnetite nanoparticles (MNPs) and the mechanism of formation and identification of magnetite nanoparticles ( Fe3O4) by examining the infrared pattern (FT-IR) obtained from Fe3O4 nanoparticles, the results of the magnetometric test (VSM) of Fe3O4 nanoparticles, X-ray diffraction pattern (XRD) of Fe3O4 nanoparticles, Field Emission Scanning Electron Microscope (FE-SEM) images obtained from Fe3O4 nanoparticles was discussed. After this stage, silica- coated iron nanoparticles (Fe3O4@SiO2) were prepared, and the infrared (FT-IR) pattern of Fe3O4@SiO2) was also investigated. It is worth mentioning that the mechanism of formation and identification of magnetic silica-coated iron nanoparticles (Fe3O4@SiO2) has been described in detail. Therefore, the obtained results indicate that the drug can be guided in a controlled and targeted manner by the magnetic field, and the results of the FE-SEM images show that the obtained product has a spherical morphology and the particle size distribution was less than 100 nm. Therefore, spherical shape and the symmetry of these particles can be helpful for their movement in the liquid mediu.

Successful preparation of a biopolymeric nanocarrier enables controlled release of antinociceptive monoterpene for local pain management after transdermal barrier permeation

AbstractDeveloping effective and targeted drug delivery systems is crucial in searching for improved pain management strategies. Here, it is shown the preparation of a nanocarrier using chitosan hydrogel, and polymeric nanocapsules loaded with linalool for enhancing transdermal permeation and targeted delivery of this antinociceptive monoterpene for the pain treatment. Extensive characterization was conducted to evaluate the properties of the nanocarrier, and several in vitro studies were performed to investigate the release kinetics of linalool from the nanocarrier and its permeation through the layers of the skin. As results, the prepared polymeric nanocarrier exhibited an average size of 160 ± 9 nm, with a polydispersion index of 0.12 ± 0.01. The kinetic study revealed that the nanocarrier effectively controlled and prolonged the release of linalool, following a pseudo‐second order model (R2 = 0.98). To evaluate the permeation of the nanocarrier through the transdermal barrier, swine ear skin was employed. The nanocarrier efficiently penetrated the transdermal barrier and successfully delivered linalool to the skin layers. Additionally, an in vivo toxicity study indicated no toxicity for the nanocarrier at the tested concentrations (<0.950 μg mL−1). The release kinetics showed a controlled and sustained release of the linalool, suggesting its potential for prolonged therapeutic effects.

Exploring a new phyto-derived nanoparticle for targeting bacterial protein EF-Tu: an integrated approach to develop antimicrobial drug

ABSTRACT The application of antibiotic medicine to save numerous lives is in jeopardy due to the alarming elevation in antibiotic-resistant organisms as a consequence of improper and imprudent usage of antibiotics. This study investigated the antibacterial efficacy of pelargonidin (PG) by employing a cost-effective nano-formulation-based targeted drug delivery system as an alternative to conventional strategies. The precise targeting of bacteria was made easier by synthesizing nano-particles of phyto-product pelargonidin (NPG) by employing poly-lactide-co-glycolide (PLGA), a biodegradable polymer. The physico-chemical characterization of NPGs was performed via AFM study and the antibacterial efficacy of NPGs tested against Escherichia coli and Staphylococcus aureus was assessed by agar disc diffusion method. Additionally, the docking platform explored in this study enabled the prediction of the ability of PG to occupy the binding pocket of EF-Tu (elongation factor thermo unstable), a vital bacterial protein that operates on a translational level. The overall results implicate that NPG was an effective drug candidate against the gram-negative bacteria E. coli and the gram-positive bacteria S. aureus according to the diameter of the inhibition zone (23 ± 0.82 mm: E. coli and 22.67 ± 1.25 mm: S. aureus). Furthermore, in silico analysis revealed that the NPG-EF-Tu complex had an excellent docking score of −9.13 Kcal/mol, indicating key amino acid residues required for interaction, and anticipating the signaling component/s involved that may be hindered by NPG, thereby leading to a decline of bacterial growth. The core phyto-compound of NPG (pelargonidin) could effectively bind to EF-Tu thereby exercising strong antimicrobial efficacy against both E. coli and S. aureus making it a potential alternative to the usage of commercial antibacterials with a history of drug-resistance.

A Novel Approach on Nanosphere Based Colon Targeted Drug Delivery System

Oral route is the most feasible and desired one, CDDS may also employ alternative methods. When administering medications directly to the colon, rectal administration is the fastest method. Rectal administration makes it challenging to reach the proximal portion of the colon. Rectal administration may potentially cause patients discomfort and result in poor compliance. Particles with a diameter between 10 and 200 nm are known as nanospheres. Nanospheres can be crystalline or amorphous in form, and they can shield a medicine from enzymatic and chemical deterioration. When treating colonic illness, targeted drugdelivery to the colon ensures direct therapy at the afflicted area with a lower dose and less systemic adverse effects and provides an appropriate environment for proteins and peptides that are susceptible to gastric fluid and digestive enzymes. It also minimizes the first pass metabolism advantage of the standard dose form and prevents gastrointestinal discomfort brought on by the ingestion of NSAIDs.
 Keywords: Nanospheres, CDDS, Nanoparticles, NSAID, gastrointestinal discomfort