Magnetic PLGA Research Articles

Simultaneous therapeutic and diagnostic applications of magnetic PLGA nanoparticles loaded with doxorubicin in rabbit.

In this study, DOX (Doxorubicin) and Fe3O4 magnetic nanocrystals (SPIONs (Superparamagnetic iron oxide nanocrystals)) were encapsulated in the PLGA-PEG: poly(lactide-co-glycolide)-b-poly(ethylene glycol) nanoparticles for theranostic purposes. The final prepared formulation which is called NPs (Nanoparticles) exhibited a particle size with a mean diameter of ~ 209nm and a sufficient saturation magnetization value of 1.65 emu/g. The NPs showed faster DOX release at pH 5.5 compared to pH 7.4. Also, the cytotoxicity effect of NPs increased compared to Free-DOX alone in C6 glioma cancer cells. For in vivo investigations, the 2.2 Kg rabbits were injected with NPs formulations via a central articular anterior vein in their ears. Furthermore, the images of rabbit organs were depicted via MR (Magnetic resonance) and fluorescent imaging techniques. A negative contrast (dark signal) was observed in T2 (Relaxation Time) weighted MR images of IV (Intravenously)-injected rabbits with NPs compared to the control ones. The organ's florescent images of NPs-injected rabbits showed a high density of red color related to the accumulation of DOX in liver and kidney organs. These data showed that the NPs have no cytotoxicity effect on the heart. Also, the results of histopathological tests of different organs showed that the groups receiving NPs and Free-DOX were almost similar and no significant difference was seen, except for the cardiac tissue in which the pathological effects of NPs were significantly less than the Free-DOX. Additionally, pharmacokinetic studies were also conducted at the sera and whole bloods of IV-injected rabbits with NPs and Free-DOX. The pharmacokinetic parameters showed that NPs could enhance the DOX retention in the serum compared to the Free-DOX. Altogether, we aimed to produce a powerful delivery nanosystem for its potential in dual therapeutic and diagnostic applications which are called theranostic agents.

A maghemite/PLGA (core/shell) nanostructure that may facilitate chemotherapy and antitumor hyperthermia

Failure of cancer therapy is typically associated to the poor accumulation of chemotherapeutics in tumor cells, the development of multidrug resistances, and the severe side effects. To beat the challenge, combined therapies against malignancies based on biodegradable nanosystems have emerged. Here, it is described the reproducible formulation of ≈ 270 nm-sized magnetic multicore PLGA particles. Characterization of the nanostructures by dynamic light scattering, electron microscopy, goniometry and electrophoresis confirmed the inclusion of hydrophobic maghemite nuclei in a polymeric nanomatrix. Adequate magnetic responsiveness was determined in vitro, while colloidal stability at 4 °C was demonstrated in short-term stability tests. Under the influence of an alternating electromagnetic field, the maghemite/PLGA (core/shell)-based colloid reached the minimum temperature of hyperthermia (≈ 42 °C) in ≈ 30 min. These heating capabilities made possible a significant decrease in the viability of T-84 cells (to ≈ 43 %). Finally, Cisplatin loading to the magnetopolymeric nanoparticles was characterized quantitatively by UV–Vis spectrophotometry (entrapment efficiency ≈ 82 %), and qualitatively by electrophoresis. The resulting Cisplatin-loaded magnetic multicore PLGA particles demonstrated a superior antitumor activity over the free chemotherapeutic in A-549 cells. These core/shell particles could be of interest for hyperthermia cancer treatment and chemotherapy.

Construction of magnetic drug delivery system and its potential application in tumor theranostics

Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.

SPION based magnetic PLGA nanofibers for neural differentiation of mesenchymal stem cells

Recently, magnetic platforms have been widely investigated in diagnostic, therapeutic and research applications due to certain properties, such as cell and tissue tracking and imaging, thermal therapy and being dirigible. In this study, the incorporation of magnetic nanoparticles (MNPs) in nanofibers has been proposed to combine the advantages of both nanofibers and MNPs to induce neural differentiation of mesenchymal stem cells. Magnetic poly (lactic-co-glycolic acid) nanofibers (containing 0%, 5% and 10% SPION) were fabricated and utilized as the matrix for the differentiation of mesenchymal stem cells (MSCs). Morphological, magnetic and mechanical properties were analyzed using FESEM, VSM and tensile test, respectively. The expression of neural markers (TUJ-1, NSE, MAP-2) was assessed quantitative and qualitatively utilizing RT-PCR and immunocytochemistry. Results confirmed the incorporation of MNPs in nanofibrous scaffold, presenting a saturation magnetization of 9.73 emu g−1. Also, with increase in magnetic particle concentration (0%–10%), tensile strength increased from 4.08 to 5.85 MPa, whereas the percentage of elongation decreased. TUJ-1 expression was 3.8 and 1.8 fold for 10% and 5% magnetic scaffold (versus non-magnetic scaffold) respectively, and the expression of NSE was 6.3 and 1.2-fold for 10% and 5%, respectively. Consequently, it seems that incorporation of magnetic biomaterial can promote the neural differentiation of MSCs, during which the augmentation of super paramagnetic iron oxide concentration from 0% to 10% accelerates the neural differentiation process.

Hydrolytic instability and low-loading levels of temozolomide to magnetic PLGA nanoparticles remain challenging against glioblastoma therapy

Temozolomide (TMZ) is the first-line chemotherapeutic agent for the treatment of newly diagnosed glioblastoma (GBM). However, chemoresistance, hydrolytic instability, and insufficient drug accumulation are major challenges limiting the effectiveness of TMZ chemotherapy. Although various nanocarriers have been offered to overcome these limitations, there are some discrepancies regarding the TMZ encapsulation efficiency (EE%). In this study, by examining the behavior of TMZ in different solvents, we aimed to confirm the loading efficiency of TMZ in the nanoparticles (NPs) and investigate the therapeutic efficacy of TMZ-loaded NPs in human GBM cell line (T98G). For this purpose, firstly, we investigated the stability of TMZ and its degradation product (AIC) to evaluate whether TMZ degradation affects the measured EE% from the supernatant (indirect method) or the NPs (direct method). Subsequently, we tried to load TMZ into magnetic poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (TMZ-m-PNPs) by modifying the synthesis parameters in a controlled manner. It was concluded that the indirect method might cause misleading results due to the high hydrolytic instability of TMZ during the NPs synthesis or washing steps. Although many modifications have been performed in the synthesis method, the EE% of TMZ ranged between 1% and 7%. In cell culture, IC50 values of free-TMZ were found for human endothelial cells (HUVEC, ∼500 μM) and human glioblastoma cells (T98G, ∼350 μM) at the 72nd h. Furthermore, cell viability was quantified using MTT, live/dead cell viability, and Annexin V-FITC/PI assays of TMZ-m-PNPs, but cytotoxicity of NPs was not dose-dependent in T98G cells. Overall, this study offers two major new insights; first, the EE% of TMZ in NPs should be determined by the direct method; second, to increase the therapeutic efficacy of TMZ-loaded NPs on GBM cells, it may be recommended not to use the PLGA-based nanocarrier system that may contribute to poor therapeutic response.

Magnetic PLGA microspheres loaded with SPIONs promoted the reconstruction of bone defects through regulating the bone mesenchymal stem cells under an external magnetic field

Superparamagnetic iron oxide nanoparticles (SPIONs) have been presented to regulate the migration and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under magnetic field (MF). However, the toxicity and short residence for the massively exposed SPIONs at bone defects compromises their practical application. Herein, SPIONs were encapsulated into PLGA microspheres to overcome these shortcomings. Three types of PLGA microspheres (PFe-I, PFe-II and PFe-III) were prepared by adjusting the feeding amount of SPIONs, in which the practical SPIONs loading amounts was 1.83%, 1.38% and 1.16%, respectively. The average diameter of the fabricated microspheres ranged from 160 μm to 200 μm, having the porous and rough surfaces displayed by SEM. Moreover, they displayed the magnetic property with a saturation magnetization of 0.16 emu/g. In vitro cell studies showed that most of BMSCs were adhered on the surface of PFe-II microspheres after 2 days of co-culture. Moreover, the osteoblasts differentiation of BMSCs was significantly promoted by PFe-II microspheres after 2 weeks of co-culture, as shown by detecting osteogenesis-related proteins expressions of ALP, COLI, OPN and OCN. Afterward, PFe-II microspheres were surgically implanted into the defect zone of rat femoral bone, followed by exposure to an external MF, to evaluate their bone repairing effect in vivo. At 6th week after treatment with PFe-II + MF, the bone mineral density (BMD, 263.97 ± 25.99 mg/cm3), trabecular thickness (TB.TH, 0.58 ± 0.08 mm), and bone tissue volume/total tissue volume (BV/TV, 78.28 ± 5.01%) at the defect zone were markedly higher than that of the PFe-II microspheres alone (BMD, 194.34 ± 26.71 mg/cm3; TB.TH, 0.41 ± 0.07 mm; BV/TV, 50.49 ± 6.41%). Moreover, the higher expressions of ALP, COLI, OPN and OCN in PFe-II + MF group were displayed in the repairing bone. Collectively, magnetic PLGA microspheres together with MF may be a promising strategy for repairing bone defects.

A doxorubicin and vincristine drug release system based on magnetic PLGA microspheres prepared by coaxial electrospray

In this study, we demonstrated a novel doxorubicin and vincristine-loaded PLGA magnetic microspheres prepared by coaxial electrospray, as a drug delivery system for osteosarcoma treatment. The results showed that microspheres had an minimum mean diameter of 0.32 ± 0.25 μm and exhibited a spherical shape. The particle size distribution changed obviously with the different dosing ways. The entrapment efficiency was found to be 65.72, 73.6 and 74.14% for different microspheres. In vitro degradation research showed that circular pores appeared gradually on the surface of particles with the increase in time, which accelerated the degradation of microspheres. CCK-8 test showed that the Fe3O4@PLGA microspheres without drug loading had almost no side effects, the cytotoxicity of Fe3O4@P/(V + D), Fe3O4@(P + D)/V and Fe3O4@(P + V)/D microspheres increased in turn, and Fe3O4@(P + V)/D microspheres with minimum particle size could significantly arrest the growth of osteosarcoma saos-2 cells. Therefore, the drug-loaded magnetic microspheres have good killing effect on osteosarcoma cell lines, which can be used as an ideal targeting treatment for postoperative adjuvant therapy of osteosarcoma.

Functionalized Magnetic PLGA Nanospheres for Targeting and Bioimaging of Breast Cancer.

Superparamagnetic iron oxide nanoparticles (SPIONs) are actively used as highly sensitive imaging probes to provide contrast in MRI. In this study, we propose the use of SPIONs encapsulated with antibody-conjugated poly(lactic-co-glycolic acid) (PLGA) as a potent theragnostic agent. The SPIONs were synthesized by a chemical co-precipitation method of ferric and ferrous ions, and subsequently encapsulated with PLGA by using an emulsification-diffusion method. Herceptin was chemically conjugated to the SPION-encapsulating PLGA nanoparticles to target the human epidermal growth factor receptor 2 (Her2/neu) overexpressing breast cancers. FACS and MR molecular imaging revealed that the Her2/neu overexpressing cell line showed a stronger contrast enhancement than the Her2/neu non-expressing cell lines, and the signal intensity of in vivo MR imaging decreased as the concentration of Herceptin increased. This strategy of encapsulating SPIONs with PLGA will be highly useful in functionalizing magnetic nanoparticles and improving the diagnostic and therapeutic efficacy of a wide array of cancer treatments.

Fabrication and in vitro evaluation of magnetic PLGA nanoparticles as a potential Methotrexate delivery system for breast cancer

Polymeric magnetic nanoparticles due to their ability in overcoming drug retention in targeted organs have been noticed for localized drug delivery. Methotrexate (MTX) is one of the most frequently used chemotherapeutic agent and disease modifying anti-rheumatic drug with high hydrophilicity feature which leads to its rapid clearance even in local injections. The aim of this study is to prepare and evaluate MTX-loaded PLGA magnetic nanoparticles (MPNPs) to overcome these obstacles. MPNPs were prepared using double emulsion-solvent evaporation method and characterized. The particles size, morphology, magnetization saturation, drug and magnetite encapsulation efficiency, MTX release pattern from particles and cytotoxicity were evaluated. Using different drug to polymer ratio, PVA concentration and stirring speed, the minimum particle size of 390 nm was acquired. Approximately, 94.57% drug encapsulation efficiency resulted by further optimization. These particles have magnetization saturation of about 43emu/g with no remanence time and showed similar cell cytotoxicity in comparison with MTX solution. Considering the appropriate in vitro properties of selected MPNPs for magnetically guided drug targeting, it seems that promising results in reducing MTX side effects maybe expectable in further in vivo studies.

Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin.

Owing to the presence of multidrug resistance in tumor cells, conventional chemotherapy remains clinically intractable. To enhance the therapeutic efficacy of chemotherapeutic agents, targeting strategies based on magnetic polymeric nanoparticles modified with targeting ligands have gained significant attention in cancer therapy. In this study, we synthesized transferrin (Tf)-modified poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) loaded with paclitaxel (PTX) and superparamagnetic nanoparticle (MNP) using a solid-in-oil-in-water solvent evaporation method, followed by Tf adsorption on the surface of NPs. The Tf-modified magnetic PLGA NPs were characterized in terms of particle morphology and size, magnetic properties, encapsulation efficiency and drug release. Furthermore, the cytotoxicity and cellular uptake of the drug-loaded magnetic PLGA NPs were evaluated in both MCF-7 breast cancer and U-87 glioma cells in vitro. We found that Tf-modified PTX-MNP-PLGA NPs showed the highest cytotoxicity effect and cellular uptake efficiency under Tf receptor mediation in both MCF-7 and U-87 cells compared to unmodified PLGA NPs and free PTX. The cellular uptake efficiency of Tf-modified magnetic PLGA NPs appeared to be facilitated by the applied magnetic field, but the difference did not reach statistical significance. This study illustrates that this proposed formulation can be used as one new alternative treatment for patients bearing inaccessible tumors.

Indocyanine Green Loaded Magnetic Plga Nanoparticles Encapsulated with Liquid Perfluorocarbon for Multimodal Imaging - Guided Photothermal Tumor Ablation

Indocyanine Green Loaded Magnetic Plga Nanoparticles Encapsulated with Liquid Perfluorocarbon for Multimodal Imaging - Guided Photothermal Tumor Ablation

In vitro and in vivo evaluation of anti-nucleolin-targeted magnetic PLGA nanoparticles loaded with doxorubicin as a theranostic agent for enhanced targeted cancer imaging and therapy

A superparamagnetic iron oxide nanoparticles (SPIONs)/doxorubicin (Dox) co-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeted with AS1411 aptamer (Apt) against murine C26 colon carcinoma cells is successfully developed via a modified multiple emulsion solvent evaporation method for theranostic purposes. The mean size of SPIO/Dox-NPs (NPs) was 130nm with a narrow particle size distribution and Dox loading of 3.0%. The SPIO loading of 16.0% and acceptable magnetic properties are obtained and analyzed using thermogravimetric and vibration simple magnetometer analysis, respectively. The best release profile from NPs was observed in PBS at pH 7.4, in which very low burst release was observed. Nucleolin is a targeting ligand to facilitate anti-tumor delivery of AS1411-targeted NPs. The Apt conjugation to NPs (Apt-NPs) enhanced cellular uptake of Dox in C26 cancer cells. Apt-NPs enhance the cytotoxicity effect of Dox followed by a significantly higher tumor inhibition and prolonged animal survival in mice bearing C26 colon carcinoma xenografts. Furthermore, Apt-NPs enhance the contrast of magnetic resonance images in tumor site. Altogether, these Apt-NPs could be considered as a powerful tumor-targeted delivery system for their potential as dual therapeutic and diagnostic applications in cancers.

Preparation and characterization of uniform-sized PLGA nanospheres encapsulated with oleic acid-coated magnetic-Fe3O4 nanoparticles for simultaneous diagnostic and therapeutic applications

In recent years, magnetic nanoparticles are increasingly studied and exploited for their potential applications as magnetic resonance imaging (MRI11Magnetic resonance imaging) contrast agents, cancer treatment, targeted therapy, delivery vectors and hyperthermia. Todays, magnetic systems based on polymeric materials such as poly(lactic-co-glycolic acid) (PLGA22Poly(lactic-co-glycolic acid)) have been of special interest for their biomedical applications. In this study, we achieved an effective method for encapsulation of sized-controlled oleic acid-coated superparamagnetic iron oxide (SPIO33Superparamagnetic iron oxide NPs44Nanoparticles) into the PLGA nanospheres via a modified multiple emulsion solvent evaporation method (O1/W1/O2/W255Oil-in-water-in- oil-in-water) resulted in development of the NPs with narrow size distribution and acceptable magnetic properties that are very vital and curtail at targeting and magnetic properties of NPs for both anti-cancer therapy and magnetic resonance imaging studies. The SPIO NPs and SPIO-PLGA nanospheres showed spherical morphology with narrow size distribution of 10nm and 130nm, respectively. SPIO-PLGA nanospheres with high SPIO loading of 18.0% and magnetic properties of 5.9 emu/g were obtained. Furthermore, SPIO-PLGA NPs enhance the contrast of relaxation time (T166Relaxation time)-weighted imaging in tumor site. The prepared SPIO NPs and magnetic PLGA nanosphere could be promising superparamagnetic nanoparticles for simultaneous diagnostic and therapeutic applications.

Dual-Targeting Magnetic PLGA Nanoparticles for Codelivery of Paclitaxel and Curcumin for Brain Tumor Therapy.

Chemotherapy is one of the most important strategies for glioma treatment. However, the "impermeability" of the blood-brain barrier (BBB) impedes most chemotherapeutics from entering the brain, thereby rendering very few drugs suitable for glioma therapy, letting alone application of a combination of chemotherapeutics. Thereby, there is a pressing need to overcome the obstacles. A dual-targeting strategy was developed by a combination of magnetic guidance and transferrin receptor-binding peptide T7-mediated active targeting delivery. The T7-modified magnetic PLGA nanoparticle (NP) system was prepared with co-encapsulation of the hydrophobic magnetic nanoparticles and a combination of drugs (i.e., paclitaxel and curcumin) based on a "one-pot" process. The combined drugs yielded synergistic effects on inhibition of tumor growth via the mechanisms of apoptosis induction and cell cycle arrest, displaying significantly increased efficacy relative to the single use of each drug. Dual-targeting effects yielded a >10-fold increase in cellular uptake studies and a >5-fold enhancement in brain delivery compared to the nontargeting NPs. For the in vivo studies with an orthotopic glioma model, efficient brain accumulation was observed by using fluorescence imaging, synchrotron radiation X-ray imaging, and MRI. Furthermore, the antiglioma treatment efficacy of the delivery system was evaluated. With application of a magnetic field, this system exhibited enhanced treatment efficiency and reduced adverse effects. All mice bearing orthotopic glioma survived, compared to a 62.5% survival rate for the combination group receiving free drugs. This dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.

Control of doxorubicin release from magnetic Poly(dl-lactide-co-glycolide) nanoparticles by application of a non-permanent magnetic field

This work studied the effect of the application time of a non-permanent magnetic field on the rate of drug release from iron oxide polymeric nanoparticles. Magnetically responsive doxorubicin loaded poly(d-lactide-co-glycolide) (PLGA) nanoparticles were synthetized by the o/w solvent extraction/evaporation method and characterized. The produced particles show spherical shapes exhibiting a size between 200 and 400 nm, a drug loading of 3.6 % (w/w) and an iron concentration of 20.7 % (w/w). Cell cytotoxicity tests showed that unloaded magnetic PLGA nanoparticles were nontoxic. Concerning the therapeutic activity, doxorubicin-loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterparts (40 against 7 % of dead cells). In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. The final amount and the rate of doxorubicin released increase with the time of field application reaching higher values for a higher number of pulses with a lower duration. Doxorubicin release mechanism has shown to be governed by Fickian diffusion in the absence of a magnetic field while in the presence of a magnetic field some controlled relaxation polymer chains might also be present. The results show that the drug release rate from magnetic PLGA nanoparticles can be modulated through the application time and the on/off cycles duration of a non-permanent magnetic field.

Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy

Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

Photophysics of an octasubstituted zinc(II) phthalocyanine incorporated into solid polymeric magnetic and non-magnetic PLGA–PVA nanoparticles

Abstract 2,3,9,10,16,17,23,24-octakis[( N , N -dimethylaminoethylsulfanyl)]phthalocyaninatozinc (II) ( S1 ) was used as a lipophilic photosensitizer to be encapsulated into biodegradable poly( d , l lactide-co-glycolide)-polyvinyl alcohol nanoparticles. The synthesis, size, and spectroscopic, photophysical, and magnetic properties of nanoparticles, were analyzed. A greater number of sonication cycles afforded smaller nanoparticles. The stabilization by means of polyvinyl alcohol of all the nanoparticles synthesized provided a negative charge to the systems in a wide pH range. The thermograms obtained by differential scanning calorimetry showed that the nanoparticles were stabilized by polyvinyl alcohol. The incorporation of magnetite nanoparticles was verified by FT-IR, magnetization measurements by means of hysteresis curves and potential Z. S1 retained its efficiency in generating singlet oxygen. The incorporation of magnetite into the nanoparticles showed an increase in singlet oxygen quantum yields due to the heavy atom effect.

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres featuring monodispersity and controllable particle size using a microchannel device

AbstractPoly(lactic‐co‐glycolic acid) (PLGA) microspheres prepared using a traditional solvent evaporation or double emulsification method are usually polydisperse with an uncontrollable particle size distribution, which brings about poor application performance. In our research, monodisperse magnetic PLGA microspheres were prepared using a microchannel device based on a water‐in‐oil‐in‐water composite emulsion. The composite emulsion was formed by injecting a dichloromethane–gelatin water‐in‐oil emulsion into a microchannel together with an external water phase, i.e. poly(vinyl alcohol) (PVA) aqueous solution. Mean particle size control of the microspheres was executed using the osmotic pressure difference between internal and external aqueous phases caused by regulating NaCl concentration in PVA aqueous phase. It is found that monodisperse magnetic PLGA microspheres with high magnetic responsiveness can be successfully prepared combining the microchannel device with composite emulsion method. Mean particle size of the microspheres with coefficient of variation value below 4.72% is controllable from 123 to 203 µm depending on the osmotic pressure. The resulting samples have pyknotic and smooth surfaces, as well as spherical appearance. These monodisperse magnetic PLGA microspheres with good superparamagnetism and magnetic mobility have potential use as drug carriers for uniform release and magnetic targeting hyperthermia in biological fields. © 2015 Society of Chemical Industry

Encapsulation of VEGF165 into magnetic PLGA nanocapsules for potential local delivery and bioactivity in human brain endothelial cells.

Angiogenesis is an important repairing mechanism in response to ischemia. The administration of pro-angiogenic proteins is an attractive therapeutic strategy to enhance angiogenesis after an ischemic event. Their labile structures and short circulation times in vivo are the main obstacles that reduce the bioactivity and dosage of such proteins at the target site. We report on poly(d,l-lactic-co-glycolic acid) (PLGA) nanocapsules (diameter < 200 nm) containing bioactive vascular endothelial growth factor-165 (VEGF165) in the inner core and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in the polymeric shell. The system showed good encapsulation efficiencies for both VEGF165 and SPIONs and a sustained protein release over 14 days. In vitro studies confirmed protein bioactivity in the form of significantly increased proliferation in human microvascular brain endothelial cell cultures once the protein was released. Through magnetic resonance imaging (MRI) measurements we demonstrated excellent T2 contrast image properties with r2 values as high as 213 mM-1 s-1. In addition, magnetic VEGF165-loaded PLGA nanocapsules could be displaced and accumulated under an external magnetic field for guiding and retention purposes. We therefore suggest that using VEGF165-loaded magnetic PLGA nanocapsules may become a new targeted protein-delivery strategy in the development of future pro-angiogenic treatments, as for instance those directed to neurorepair after an ischemic event.

Surface modification of HSA containing magnetic PLGA nanoparticles by poloxamer to decrease plasma protein adsorption

Lifetime prolongation for hydrophobic drug carriers has been the focus of interest for many years. Poloxamer (Pluronic F68, PF68) has been employed in this study for modifying the surface of magnetic poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with human serum albumin (HSA) model drug. Surface characteristics of untreated and PF68 treated NPs were analyzed by size, zeta potential and electrophoretic mobility studies. UV–vis spectroscopic analysis, isothermal titration calorimetry (ITC) and dynamic light scattering methods were used to investigate serum protein (bovine serum albumin, BSA) adsorption. Results showed the successful surface attachment of PF68. Among different concentrations (0.1–1%, wt/vol) of PF68 studied, 0.5% was found to be the most useful, since a higher concentration can issue in micelle formation. 50% less BSA tended to be adsorbed on the treated NPs in comparison to the untreated ones.