Diffusion of curcumin in PLGA-based carriers for drug delivery: a molecular dynamics study.

CONTEXT: The rapid growth and diversification of drug delivery systems have been significantly supported by advancements in micro- and nano-technologies, alongside the adoption of biodegradable polymeric materials like poly(lactic-co-glycolic acid) (PLGA) as microcarriers. These developments aim to reduce toxicity and enhance target specificity in drug delivery. The use of in silico methods, particularly molecular dynamics (MD) simulations, has emerged as a pivotal tool for predicting the dynamics of species within these systems. This approach aids in investigating drug delivery mechanisms, thereby reducing the costs associated with design and prototyping. In this study, we focus on elucidating the diffusion mechanisms in curcumin-loaded PLGA particles, which are critical for optimizing drug release and efficacy in therapeutic applications. METHODS: We utilized MD to explore the diffusion behavior of curcumin in PLGA drug delivery systems. The simulations, executed with GROMACS, modeled curcumin molecules in a representative volume element of PLGA chains and water, referencing molecular structures from the Protein Data Bank and employing the CHARMM force field. We generated PLGA chains of varying lengths using the Polymer Modeler tool and arranged them in a bulk-like environment with Packmol. The simulation protocol included steps for energy minimization, T and p equilibration, and calculation of the isotropic diffusion coefficient from the mean square displacement. The Taguchi method was applied to assess the effects of hydration level, PLGA chain length, and density on diffusion. RESULTS: Our results provide insight into the influence of PLGA chain length, hydration level, and polymer density on the diffusion coefficient of curcumin, offering a mechanistic understanding for the design of efficient drug delivery systems. The sensitivity analysis obtained through the Taguchi method identified hydration level and PLGA density as the most significant input parameters affecting curcumin diffusion, while the effect of PLGA chain length was negligible within the simulated range. We provided a regression equation capable to accurately fit MD results. The regression equation suggests that increases in hydration level and PLGA density result in a decrease in the diffusion coefficient.

Clinical Trials for Oral, Inhaled and Intravenous Drug Delivery System for Lung Cancer and Emerging Nanomedicine-Based Approaches.

Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.

Histologic evaluation of a catheter coated with paclitaxel PLGA nanoparticles in the internal jugular veins of rats.

The aim of this study is to investigate the potential impact of catheterization on intimal hyperplasia and explore the efficacy of Paclitaxel loaded PLGA nanoparticles (PTX-NPs) in preventing stenosis at the site of venous injury. Under general anesthesia, Central Venous Catheters were inserted into the rat's right internal jugular veins (IJV) using the cut-down technique. Twenty bare catheters (C) and twenty PTX-NPs coated catheters (P) were assigned to one of four groups (C2, C4, P2, or P4) based on catheter type and expected survival time. 2 or 4 weeks after surgery, IJVs were completely harvested by formalin fixation and gelatin infusion and slides were stained with H&E (Haematoxylin and Eosin) and Masson's technique. The P2 (Paclitaxel coating, 2 weeks) group showed the most proliferation among the four groups and the P4 (Paclitaxel coating, 4 weeks) showed a tendency to decrease proliferation. Additionally, the lumen size in the P4 group was about 6% smaller than in the P2 group, and there was a lower prevalence of stenotic grade in the P4 group. Our study suggests that PTX-NPs coated catheters may be effective in preventing venous stenosis if the intended usage is prolonged, rather than for a short-term period. Graphical abstract: Schematic representation of catheter functionalization and coating of PTX-NPs on Catheter. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00282-y.

Protection of Hearing Loss in Ototoxic Mouse Model Through SPIONs and Dexamethasone-Loaded PLGA Nanoparticle Delivery by Magnetic Attraction.

Background: Ototoxicity currently has no available treatment other than medication withdrawal as soon as toxicity is suspected. The human inner ear organs have little potential for regeneration; thus, ototoxicity-induced hair cell injury is deemed permanent. Dexamethasone (Dexa) is a synthetic steroid analog that has significant potential for otoprotection in the treatment of various inner ear diseases; however, its low absorption into the inner ear prevents significant recovery of function. Nanoparticles facilitate targeted drug delivery, stabilize drug release, and increase half-life of the drug. Methods: This study aimed to develop poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded superparamagnetic iron oxide nanoparticles (SPIONs) and Dexa (PSD-NPs) to control localized drug delivery by magnetic attraction in the treatment of ototoxicity-induced hearing loss. PSD-NPs and without SPIONs (PD-NPs) were prepared using a nanoprecipitation method. Results: Using an inner ear simulating system, we confirmed that PSD-NPs has an otoprotective effect in organotypic culture that is enhanced by magnetic attraction. PSD-NPs delivered via intrabullar injection in a magnetic field penetrated the inner ear and prevented hearing loss progression to a greater degree than equivalent doses of Dexa or PSD-NPs alone (day 28: ototoxic: 80.0 ± 0.0 dB; Dexa 100: 60.0 ± 15.5 dB; PSD 100: 50.0 ± 8.2 dB; PSD 100 with magnet: 22.5 ± 5.0 dB; P < 0.05). The protective effects were confirmed in various in vivo and in vitro models of ototoxicity. Conclusion: Our findings suggest that SPIONs with Dexa and magnetic field application prevent the progression of ototoxicity-induced hearing loss through anti-apoptotic mechanisms in the inner ear.

Targeted thrombolysis by magnetoacoustic particles in photothrombotic stroke model.

BACKGROUND: Recombinant tissue plasminogen activator (rtPA) has a short half-life, and additional hemorrhagic transformation (HT) can occur when treatment is delayed. Here, we report the design and thrombolytic performance of 3 [Formula: see text]m discoidal polymeric particles loaded with rtPA and superparamagnetic iron oxide nanoparticles (SPIONs), referred to as rmDPPs, to address the HT issues of rtPA. METHODS: The rmDPPs consisted of a biodegradable polymeric matrix, rtPA, and SPIONs and were synthesized via a top-down fabrication. RESULTS: The rmDPPs could be concentrated at the target site with magnetic attraction, and then the rtPA could be released under acoustic stimulus. Therefore, we named that the particles had magnetoacoustic properties. For the in vitro blood clot lysis, the rmDPPs with magnetoacoustic stimuli could not enhance the lytic potential compared to the rmDPPs without stimulation. Furthermore, although the reduction of the infarcts in vivo was observed along with the magnetoacoustic stimuli in the rmDPPs, more enhancement was not achieved in comparison with the rtPA. A notable advantage of rmDPPs was shown in delayed administration of rmDPPs at poststroke. The late treatment of rmDPPs with magnetoacoustic stimuli could reduce the infarcts and lead to no additional HT issues, while rtPA alone could not show any favorable prognosis. CONCLUSION: The rmDPPs may be advantageous in delayed treatment of thrombotic patients.

Cavitation-assisted sonothrombolysis by asymmetrical nanostars for accelerated thrombolysis.

Sonothrombolysis with recombinant tissue plasminogen activator (rtPA) and microbubbles has been widely studied to enhance thrombolytic potential. Here, we report different sonothrombolysis strategy in nanoparticles using microbubbles cavitation. We found that different particles in shape exhibited different reactivity toward the cavitation, leading to a distinct sonothrombolytic potential. Two different gold nanoparticles in shape were functionalized with the rtPA: rtPA-functionalized gold nanospheres (NPt) and gold nanostars (NSt). NPt could not accelerate the thrombolytic potential with a sole acoustic stimulus. Importantly, NSt enhanced the potential with acoustic stimulus and microbubble-mediated cavitation, while NPt were not reactive to cavitation. Coadministration of NSt and microbubbles resulted in a dramatic reduction of the infarcts in a photothrombotic model and recovery in the cerebral blood flow. Given the synergistic effect and in vivo feasibility of this strategy, cavitation-assisted sonothrombolysis by asymmetrical NSt might be useful for treating acute ischemic stroke.

Improved survival rate and minimal side effects of doxorubicin for lung metastasis using engineered discoidal polymeric particles.

Despite advances in cancer therapy, the discovery of effective cancer treatments remains challenging. In this study, a simple method was developed to increase the efficiency of doxorubicin (DOX) delivery in a lung metastasis model. This method comprises a simple configuration to increase the delivery efficiency via precise engineering of the size, shape, loading content, and biodegradability of the drug delivery system. This system had a 3 µm discoidal shape and exerted approximately 90% burst release of the drug within the first 24 h. There was no cytotoxicity of the drug carrier up to a concentration of 1 mg ml-1, and DOX from the carrier was delivered into the cancer cells, exhibiting an anticancer effect comparable to that of the free drug. The ex vivo results revealed a strong correlation between the location of cancer cells in the lung and the location of DOX delivered by this drug delivery system. These drug carriers were confirmed to intensively deliver DOX to cancer cells in the lung, with minimal off-target effects. These findings indicate that this delivery system can be a new approach to improving the survival rate and reducing the side effects caused by anticancer drugs without the use of targeting ligands and polyethylene glycol.

Indocyanine Green-Loaded PLGA Nanoparticles Conjugated with Hyaluronic Acid Improve Target Specificity in Cervical Cancer Tumors.

PURPOSE: Indocyanine green (ICG) is a promising agent for intraoperative visualization of tumor tissues and sentinel lymph nodes in early-stage gynecological cancer. However, it has some limitations, including a short half-life and poor solubility in aqueous solutions. This study aimed to enhance the efficacy of near-infrared (NIR) fluorescence imaging by overcoming the shortcomings of ICG using a nano-drug delivery system and improve target specificity in cervical cancer. MATERIALS AND METHODS: ICG and poly(lactic-co-glycolic acid) (PLGA) conjugated with polyethylenimine (PEI) were assembled to enhance stability. Hyaluronic acid (HA) was coated on PEI-PLGA-ICG nanoparticles to target CD44-positive cancer cells. The manufactured HA-ICG-PLGA nanoparticles (HINPs) were evaluated in vitro and in vivo on cervical cancer cells (SiHa; CD44+) and human dermal cells (ccd986sk; CD44-), respectively, using NIR imaging to compare intracellular uptake and to quantify the fluorescence intensities of cells and tumors. RESULTS: HINPs were confirmed to have a mean size of 200 nm and a zeta-potential of 33 mV using dynamic light scattering. The stability of the HINPs was confirmed at pH 5.0-8.0. Cytotoxicity assays, intracellular uptake assays, and cervical cancer xenograft models revealed that, compared to free ICG, the HINPs had significantly higher internalization by cervical cancer cells than normal cells (p<0.001) and significantly higher accumulation in tumors (p<0.001) via CD44 receptor-mediated endocytosis. CONCLUSION: This study demonstrated the successful application of HINPs as nanocarriers for delivering ICG to CD44-positive cervical cancer, with improved efficacy in NIR fluorescence imaging.

Porous discoidal polymeric particles for effective drug delivery minimizing phagocytosis.

Curcumin has great potential in cancer treatment and prevention. However, free curcumin for anticancer effect is limited due to its low water solubility and instability. Delivery of free curcumin using biodegradable and biocompatible polymers, such as poly (lactic-co-glycolic acid) (PLGA), can improve these undesirable problems. In this study, a top-down fabrication method using PLGA was employed to deliver free curcumin, engineering size, shape, and surface properties. As a result, porous discoidal polymeric particles (DPPs) were produced in ammonium bicarbonate with a hydrodynamic diameter of 5 µm and a negatively charged surface. The loading amount of free curcumin in the porous DPPs was higher than non-porous DPPs. In vitro drug release study showed that curcumin release from porous DPPs was 1.4-fold higher than non-porous ones. The confocal microscopy and flow cytometry results demonstrated that porous DPPs decrease phagocytosis by macrophages than non-porous ones. This study suggests that porous DPPs have significant advantages for effective drug delivery of curcumin, minimizing phagocytosis.

Biodistribution of poly clustered superparamagnetic iron oxide nanoparticle labeled mesenchymal stem cells in aminoglycoside induced ototoxic mouse model.

Recently, application of stem cell therapy in regenerative medicine has become an active field of study. Mesenchymal stem cells (MSCs) are known to have a strong ability for homing. MSCs labeled with superparamagnetic iron oxide nanoparticles (SPIONs) exhibit enhanced homing due to magnetic attraction. We have designed a SPION that has a cluster core of iron oxide-based nanoparticles coated with PLGA-Cy5.5. We optimized the nanoparticles for internalization to enable the transport of PCS nanoparticles through endocytosis into MSCs. The migration of magnetized MSCs with SPION by static magnets was seen in vitro. The auditory hair cells do not regenerate once damaged, ototoxic mouse model was generated by administration of kanamycin and furosemide. SPION labeled MSC's were administered through different injection routes in the ototoxic animal model. As result, the intratympanic administration group with magnet had the highest number of cells in the brain followed by the liver, cochlea, and kidney as compared to those in the control groups. The synthesized PCS (poly clustered superparamagnetic iron oxide) nanoparticles, together with MSCs, by magnetic attraction, could synergistically enhance stem cell delivery. The poly clustered superparamagnetic iron oxide nanoparticle labeled in the mesenchymal stem cells have increased the efficacy of homing of the MSC's to the target area by synergetic effect of magnetic attraction and chemotaxis (SDF-1/CXCR4 axis). This technique allows delivery of the stem cells to the areas with limited vasculatures. The nanoparticle in the biomedicine allows drug delivery, thus, the combination of nanomedicince together with the regenerative medicine will provide highly effective therapy.

Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles.

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. RESULTS: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. CONCLUSIONS: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

Variable Membrane Dielectric Polarization Characteristic in Individual Live Cells.

Investigation of the dielectric properties of cell membranes plays an important role in understanding the biological activities that sustain cellular life and realize cellular functionalities. Herein, the variable dielectric polarization characteristics of cell membranes are reported. In controlling the dielectric polarization of a cell using dielectrophoresis force spectroscopy, different cellular crossover frequencies were observed by modulating both the direction and sweep rate of the frequency. The crossover frequencies were used for the extraction of the variable capacitance, which is involved in the dielectric polarization across the cell membranes. In addition, this variable phenomenon was investigated by examining cells whose membranes were cholesterol-depleted with methyl-ß-cyclodextrin, which verified a strong correlation between the variable dielectric polarization characteristics and membrane composition changes. This study presented the dielectric polarization properties in live cells' membranes that can be modified by the regulation of external stimuli and provided a powerful platform to explore cellular membrane dielectric polarization.

Therapeutic Efficacy of Curcumin Enhanced by Microscale Discoidal Polymeric Particles in a Murine Asthma Model.

Curcumin is considered a potential anti-asthmatic agent owing to its anti-inflammatory properties. The objective of the present study was to prepare curcumin-containing poly(lactic-co-glycolic acid)-based microscale discoidal polymeric particles (Cur-PLGA-DPPs) and evaluate their anti-asthmatic properties using a murine asthma model. Cur-PLGA-DPPs were prepared using a top-down fabrication method. The prepared Cur-PLGA-DPPs had a mean particle size of 2.5 ± 0.4 µm and a zeta potential value of -34.6 ± 4.8 mV. Ex vivo biodistribution results showed that the Cur-PLGA-DPPs mainly accumulated in the lungs and liver after intravenous injection. Treatment with Cur-PLGA-DPPs effectively suppressed the infiltration of inflammatory cells in bronchoalveolar lavage fluid, and reduced bronchial wall thickening and goblet-cell hyperplasia compared to those in the phosphate-buffered-saline-treated control group. No significant changes in hematology and blood biochemistry parameters were observed after treatment with Cur-PLGA-DPPs. At equal curcumin concentrations, treatment with Cur-PLGA-DPPs exhibited better therapeutic efficacy than treatment with free curcumin. Our results suggest that the microscale Cur-PLGA-DPPs can be potentially used as a lung-targeted asthma therapy.

A novel automatic segmentation and tracking method to measure cellular dielectrophoretic mobility from individual cell trajectories for high throughput assay.

BACKGROUND AND OBJECTIVE: The dielectrophoresis (DEP) technique is increasingly being recognised as a potentially valuable tool for non-contact manipulation of numerous cells as well as for biological single cell analysis with non-invasive characterisation of a cell's electrical properties. Several studies have attempted to track multiple cells to characterise their cellular DEP mobility. However, they encountered difficulties in simultaneously tracking the movement of a large number of individual cells in a bright-field image sequence because of interference from the background electrode pattern. Consequently, this present study aims to develop an automatic system for imaging-based characterisation of cellular DEP mobility, which enables the simultaneous tracking of several hundred of cells inside a microfluidic device. METHODS: The proposed method for segmentation and tracking of cells consists of two main stages: pre-processing and particle centre localisation. In the pre-processing stage, background subtraction and contrast enhancement were performed to distinguish the cell region from the background image. In the particle centre localisation stage, the unmarked cell was automatically detected via graph-cut algorithm-based K-means clustering. RESULTS: Our algorithm enabled segmentation and tracking of numerous Michigan Cancer Foundation-7 (MCF-7) cell trajectories while the DEP force was oscillated between positive and negative. The cell tracking accuracy and cell count capability was at least 90% of the total number of cells with the newly developed algorithm. In addition, the cross-over frequency was measured by analysing the segmented and tracked trajectory data of the cellular movements caused by the positive and negative DEP force. The measured cross-over frequency was compared with previous results. The multi-cellular movements investigation based on the measured cross-over frequency was repeated until the viability of cells was unchanged in the same environment as in a microfluidic device. The results were statistically consistent, indicating that the developed algorithm was reliable for the investigation of DEP cellular mobility. CONCLUSION: This study developed a powerful platform to simultaneously measure the DEP-induced trajectories of numerous cells, and to investigate in a robust, efficient, and accurate manner the DEP properties at both the single cell and cell ensemble level.

Endocytic trafficking of polymeric clustered superparamagnetic iron oxide nanoparticles in mesenchymal stem cells.

The technology of directing nanoparticles to specific locations in the body continues to be an area of great interest in a myriad of research fields. In the present study, we have developed nanoparticles and a method that allows the nanoparticles to move to specific sites by simultaneously utilizing the homing ability and magnetism of stem cells. Polymeric clustered SPIO (PCS) nanoparticles are composed of a superparamagnetic iron oxide nanoparticle (SPION) cluster core coated with poly lactic-co-glycolic acid (PLGA) and labeled with the fluorescent dye Cy5.5 for tracking. PCS is designed to be internalized by stem cells via endocytosis and then moved to the desired subcellular location through magnetism. Here, we investigated the interactions between SPIONs and mesenchymal stem cells (MSCs), including their absorption mechanism and subcellular localization. Exposure to the nanoparticles at 40 µg/mL for over 96 h did not affect cell survival or differentiation. We used a variety of endocytosis inhibitors and identified the potential cellular internalization pathway of SPIONs to be clathrin-mediated endocytosis. Antibodies to organelles were used to accumulate lysosomes through early and late endosomes. PCS at 40 µg/mL was internalized and stored without significant deleterious effects on stem cells, indicating that MSCs can act as an effective nanoparticle carrier. These findings also demonstrate the successful localization of the novel particles using magnetic attraction.

Engineered iron oxide nanoparticles to improve regenerative effects of mesenchymal stem cells.

ABSTRACT: Mesenchymal stem cells (MSCs) based therapies are a major field of regenerative medicine. However, the success of MSC therapy relies on the efficiency of its delivery and retention, differentiation, and secreting paracrine factors at the target sites. Recent studies show that superparamagnetic iron oxide nanoparticles (SPIONs) modulate the regenerative effects of MSCs. After interacting with the cell membrane of MSCs, SPIONs can enter the cells via the endocytic pathway. The physicochemical properties of nanoparticles, including size, surface charge (zeta-potential), and surface ligand, influence their interactions with MSC, such as cellular uptake, cytotoxicity, homing factors, and regenerative related factors (VEGF, TGF-ß1). Therefore, in-depth knowledge of the physicochemical properties of SPIONs might be a promising lead in regenerative and anti-inflammation research using SPIONs mediated MSCs. In this review, recent research on SPIONs with MSCs and the various designs of SPIONs are examined and summarized. GRAPHIC ABSTRACT: A graphical abstract describes important parameters in the design of superparamagnetic iron oxide nanoparticles, affecting mesenchymal stem cells. These physicochemical properties are closely related to the mesenchymal stem cells to achieve improved cellular responses such as homing factors and cell uptake.

Overcoming Nanoparticle-Mediated Complement Activation by Surface PEG Pairing.

Many PEGylated nanoparticles activate the complement system, which is an integral component of innate immunity. This is of concern as uncontrolled complement activation is potentially detrimental and contributes to disease pathogenesis. Here, it is demonstrated that, in contrast to carboxyPEG2000-stabilized poly(lactic-co-glycolic acid) nanoparticles, surface camouflaging with appropriate combinations and proportions of carboxyPEG2000 and methoxyPEG550 can largely suppress nanoparticle-mediated complement activation through the lectin pathway. This is attributed to the ability of the short, rigid methoxyPEG550 chains to laterally compress carboxyPEG2000 molecules to become more stretched and assume an extended, random coil configuration. As supported by coarse-grained molecular dynamics simulations, these conformational attributes minimize statistical protein binding/intercalation, thereby affecting sequential dynamic processes in complement convertase assembly. Furthermore, PEG pairing has no additional effect on nanoparticle longevity in the blood and macrophage uptake. PEG pairing significantly overcomes nanoparticle-mediated complement activation without the need for surface functionalization with complement inhibitors.

Top-down fabrication-based nano/microparticles for molecular imaging and drug delivery.

Recent breakthroughs in nanoparticle research have led to improved drug delivery and have overcome problems associated with normal drug delivery methods. Optimizing the design of nanoparticles in terms of controlled size, shape, and surface chemistry of nanoparticles can maximize the therapeutic efficacy. To maximize therapeutic effects, advanced formulation and fabrication methods have been developed. Biomedical applications of nanoparticles produced using the new fabrication techniques, including drug delivery and molecular imaging, have been widely explored. This review highlights the simple and versatile manufacturing techniques that can be used in the development of new types of nanoparticles that have strictly controlled physiochemical properties and their multifaceted advantages in drug delivery and molecular imaging.

Biodegradable micro-sized discoidal polymeric particles for lung-targeted delivery system.

Various types of particle-based drug delivery systems have been explored for the treatment of pulmonary diseases; however, bio-distribution and elimination of the particles should be monitored for better understanding of their therapeutic efficacy and safety. This study aimed to characterize the biological properties of micro-sized discoidal polymeric particles (DPPs) as lung-targeted drug delivery carriers. DPPs were prepared using a top-down fabrication approach and characterized by assessing size and zeta potential. They were labeled with zirconium-89 (89Zr), and bio-distribution studies and PET imaging were performed for 7 days after intravenous administration. Their hydrodynamic size was 2.8 ±â€¯6.1 µm and average zeta potential was -39.9 ±â€¯5.39 mV. At doses of 5, 12.5, and 25 mg/kg, they showed no acute toxicity in nude mice. Desferrioxamine (DFO)-functionalized 89Zr-labeled DPPs gave a decay-corrected radiochemical yield of 82.1 ±â€¯0.2%. Furthermore, 89Zr-DPPs, from chelate-free labeling methods, showed a yield of 48.5 ±â€¯0.9%. Bio-distribution studies and PET imaging showed 89Zr-DFO-DPPs to be mainly accumulated in the lungs and degraded within 3 d of injection. However, 89Zr-DFO-DPPs showed significantly low uptake in the bone. Overall, our results suggested micro-sized DPPs as promising drug delivery carriers for the targeted treatment of various pulmonary diseases.

Strategies to enhance efficacy of SPION-labeled stem cell homing by magnetic attraction: a systemic review with meta-analysis.

Stem cells possess a promising potential in the clinical field. The application and effective delivery of stem cells to the desired target organ or site of injury plays an important role. This review describes strategies on understanding the effective delivery of stem cells labeled with superparamagnetic iron oxide nanoparticles (SPION) using an external magnet to enhance stem cell migration in vivo and in vitro. Fourteen total publications among 174 articles were selected. Stem cell type, SPION characteristics, labeling time, and magnetic force in vivo are considered important factors affecting the effective delivery of stem cells to the homing site. Most papers reported that the efficiency was increased when magnet is applied compared to those without. Ten studies analyzed the homing competency of SPION-labeled MSCs in vitro by observing the migration of the cell toward the external magnet. In cell-based experiments, the mechanism of magnetic attraction, the kind of nanoparticles, and various stem cells were studied well. Meta-analysis has shown the mean size of nanoparticles and degree of recovery or regeneration of damaged target organs upon in vivo studies. This strategy may provide a guideline for designing studies involving stem cell homing and further expand stem cell.