Biodegradable microspheres as carriers for native superoxide dismutase and catalase delivery

Modification of release rates of cyclosporin A from polyl( L-lactic acid) microspheres by fatty acid esters and in-vivo evaluation of the microspheres

Comparative study on sustained release of human growth hormone from semi-crystalline poly( l-lactic acid) and amorphous poly( d, l-lactic-co-glycolic acid) microspheres: morphological effect on protein release

In this work, magnetite (Fe(3)O(4)) nanoparticles with an average size 10 nm modified by sodium oleate were prepared by the modified controlled chemical coprecipitation method, which can be well dispersed in water and linked well with protein molecules because of the presence of -COOH on their surface. Then magnetic poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microspheres containing interferon alpha-2b (IFN-a-2b) were prepared by the modified water-in-oil-in-water solvent evaporation procedure. X-ray powder diffraction analysis, particle size analysis, transmission electron microscopy, scanning electron microscopy, and vibrating-sample magnetometer (VSM) analysis were carried out to examine phase composition, surface and interior morphology, size and size distribution, and magnetic properties of the magnetic microspheres. Also the effects of some important parameters on the magnetic biodegradable microspheres were investigated, such as magnetite dosage in the preparation system, stirring rate of the suspension medium, and concentration of the external aqueous phase. And the antiviral activity of IFN-a-2b encapsulated in the magnetic polymeric microspheres was evaluated by the vesicular stomatitis virus (VSV) cytopathicity inhibition assay. The results showed that the properties of IFN-loaded magnetic PLGA and PLA microspheres were better than the conventional protein-loaded polymeric microspheres, such as perfect magnetic properties, higher protein encapsulation efficiency, and less effect on the antiviral activity of protein. These indicated that the magnetic PLA and PLGA microspheres containing IFN-a-2b exhibited strong potential as targeted-drug delivery vehicles, which could be rapidly localized to the immunization-related tissues easily by an external magnetic field.

Transarterial chemoembolization (TACE) is a therapeutic approach to address hepatocellular carcinoma by obstructing the blood supply to the tumor using embolic agents and improving the local delivery of anticancer agents. Size-calibrated polymeric microspheres (MSs) termed drug-eluting beads (DEBs) are the most prevalent solid embolic materials; however, their limitations include insufficient X-ray visibility or biodegradability. In this study, size-controlled polymeric MSs with inherent radiopacity and biodegradability were created, and their embolic effect was assessed. Poly(lactide-co-glycolide) MSs (PLGA MSs) incorporating a hydrophobic X-ray contrast agent and an anticancer drug were produced by the w/o/w emulsion process. Their sizes were exactly calibrated to 71.40 ± 32.18 and 142.66 ± 59.92 μm in diameter, respectively, which were confirmed to have sizes similar to the clinically available DEBs. The iodine content of PLGA MSs was calculated as 144 mgI/g, and the loading quantity of the drug was 1.33%. Manufactured PLGA MSs were gradually degraded for 10 weeks and consistently released the anticancer drug. Following the PLGA MSs injection into the renal artery of New Zealand white rabbit test subjects, their deliverability to the targeted vessel through the microcatheter was confirmed. Injected PLGA MSs were clearly imaged through the real-time X-ray device without blending any contrast agents. The embolic effect of the PLGA MSs was ultimately established by the atrophy of an embolized kidney after 8 weeks. Consequently, the designed PLGA MS is anticipated to be an encouraging prospect to address hepatocellular carcinoma.

5-Fluorouracil plasma levels and biodegradation of subcutaneously injected drug-loaded microspheres prepared by spray-drying poly( d, l-lactide) and poly( d, l-lactide-co-glycolide) polymers

Considering the significance of effective antigen presentation for boosting immune responses, it is essential to develop delivery systems for antigen presenting cells (APCs; dendritic cells and macrophages). As a simple and facile way for improving delivery efficiency of PLGA microspheres (MS) into APCs, we fabricated exosome-conjugated PLGA MS via polydopamine coating in this study. Spherical micro-sized particles were first prepared by conventional water-in oil-in water (W1/O/W2) double emulsion and solvent evaporation methods and were observed by scanning electron microscopy (SEM). With increasing model protein (ovalbumin)/MS weight ratios, higher amounts of ovalbumin (OVA) were immobilized onto MS. After exosome (EXO) conjugation to MS via polydopamine coating, the amount of nitrogen was significantly increased on the surface of MS, indicating that EXO were successfully conjugated onto MS. EXO-coated dopamine MS (EXO-Dopa MS) exhibited significantly improved delivery into DC2.4 cells and RAW264.7 cells, compared with bare MS and Dopa MS. Therefore, EXO-Dopa MS could be used as effective carriers of immune stimulating biomolecules into APCs for cancer immunotherapy.

Applications of poly(l-lactide) (PLA) and poly(d,l-lactide-co-glycolide) (PLGA) microspheres are widely used in the biomedical and pharmaceutical fields. The effects of PLA/PLGA on microsphere properties when using conventional particulate preparation methods are not easily defined due to the uncontrollable particle size and size distribution. This study was aimed to synthesize uniform PLA and PLGA microspheres using a phenol formaldehyde resin-based microfluidic chip, which has the advantage of being solvent-resistant, flexible, and is readily disassembled for cleaning. The proposed chip can rapidly fabricate reproducible PLA and PLGA microspheres. Uniform emulsion droplets can be achieved by hydrodynamic flow focusing. After solvent evaporation, the free-flowing PLA and PLGA microspheres have a high level of morphological uniformity and size, allowing for a clear comparison of material effects. The results indicate that the sizes of the PLA and PLGA microspheres for the various flow rates of dispersed/continuous phases are very similar. The PLA/PLGA materials do not have a significant effect on particle size, but the particle surface indicates a different morphology. The result of the cytotoxicity evaluation shows no difference between PLA and PLGA and ensures the biocompatibility of both prepared PLA and PLGA microspheres for biomedical and pharmaceutical applications in the future.

Doxorubicin-loaded poly(lactic-co-glycolic acid) microspheres prepared using the solid-in-oil-in-water method for the transarterial chemoembolization of a liver tumor

Polymer based microspheres of aceclofenac as sustained release parenterals for prolonged anti-inflammatory effect

Purpose: Alendronate sodium, used systemically as a bone protective agent, proved to also be effective locally in various dental bone applications. Development of alendronate-loaded microspheres with high loading efficiency for such applications would be greatly challenged by the hydrophilicity and low MW of the drug. The aim of this study was to incorporate alendronate sodium, into poly (lactide-co-glycolide) (PLGA) microspheres (MS) with high loading efficiency.Methods: Three multiple emulsion methods: water-in-oil-in-water (W/O/W), water-in-oil-in-oil (W/O1/O2) and solid-in-oil-in-oil (S/O1/O2) were tested. In addition to entrapment efficiency, MS were characterized for surface morphology, particle size, in vitro drug release and in vitro degradation of the polymer matrix. Alendronate microspheres with maximum drug loading and good overall in vitro performance were obtained using the W/O1/O2 emulsion technique.Results: Drug release from the microspheres exhibited a triphasic release pattern over a period of 13 days, the last fast release phase being associated with more rapid degradation of the PLGA matrix.Conclusions: Biocompatible, biodegradable PLGA microspheres incorporating alendronate sodium with high loading efficiency obtained in this study may offer promise as a delivery system for bisphosphonates in dental and probably other clinical applications.

Biodegradation and biocompatibility of PLA and PLGA microspheres

Biodegradation and biocompatibility of PLA and PLGA microspheres

Fabrication of hollow porous PLGA microspheres for controlled protein release and promotion of cell compatibility

Biodegradable microspheres as controlled-release tetanus toxoid delivery systems

Local as well as systemic therapy is often used to treat bacterial lung infections. Delivery of antibiotics to the vascular side of infected lung tissue using lung-targeting microspheres (MS) is a good alternative to conventional administration routes, allowing for localized high levels of antibiotics. This delivery route can also complement inhaled antibiotic therapy, especially in the case of compromised lung function. We prepared and characterized monodisperse poly(lactic-co-glycolic acid) (PLGA) MS loaded with levofloxacin using a flow-focusing glass microfluidic chip. In vitro characterization showed that the encapsulated LVX displayed a biphasic controlled release during 5 days and preserved its antibacterial activity. The MS degradation was investigated in vitro by cross-sectioning the MS using a focused ion beam scanning electron microscope and in vivo by histological examination of lung tissue from mice intravenously administered with the MS. The MS showed changes in the surface morphology and internal matrix, whereas the degradation in vivo was 3 times faster than that in vitro. No effect on the viability of endothelial and lung epithelial cells or hemolytic activity was observed. To evaluate the pharmacokinetics and biodistribution of the MS, complete quantitative imaging of the 111indium-labeled PLGA MS was performed in vivo with single-photon emission computed tomography imaging over 10 days. The PLGA MS distributed homogeneously in the lung capillaries. Overall, intravenous administration of 12 μm PLGA MS is suitable for passive lung targeting and pulmonary therapy.