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International Journal of Molecular... Aug 2021Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for... (Review)
Review
Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.
Topics: Animals; Drug Carriers; Drug Compounding; Drug Delivery Systems; Humans; Microspheres; Peptide Fragments; Polyesters; Polylactic Acid-Polyglycolic Acid Copolymer; Proteins
PubMed: 34445587
DOI: 10.3390/ijms22168884 -
Advanced Science (Weinheim,... May 2023Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone...
Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and is featured by the imbalance between intraosseous vascularization and bone metabolism. In this study, a pH-responsive shell-core structured micro/nano-hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics and ionic cross-linking technology are developed. This micro/nano-hydrogel microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to bone tissue, and thus negatively affecting intraosseous angiogenesis and osteoclastogenesis. According to biodistribution data, PDAP@Alg/Cs can successfully enhance drug intestinal absorption and bioavailability through intestine adhesion and bone targeting after oral administration. In vitro and in vivo experiments reveal that PDAP@Alg/Cs promoted type H vessel formation and inhibited bone resorption, effectively mitigating bone loss by activating HIF-1α/VEGF signaling pathway and promoting heme oxygenase-1 (HO-1) expression. In conclusion, this novel oral micro/nano-hydrogel microsphere system can simultaneously accelerate intraosseous vascularization and decrease bone resorption, offering a brand-new approach to prevent postmenopausal osteoporosis.
Topics: Female; Humans; Hydrogels; Microspheres; Osteoporosis, Postmenopausal; Tissue Distribution; Bone and Bones; Bone Resorption
PubMed: 36967561
DOI: 10.1002/advs.202207381 -
International Journal of Nanomedicine 2013Porous microspheres have drawn great attention in the last two decades for their potential applications in many fields, such as carriers for drugs, absorption and... (Review)
Review
Porous microspheres have drawn great attention in the last two decades for their potential applications in many fields, such as carriers for drugs, absorption and desorption of substances, pulmonary drug delivery, and tissue regeneration. The application of porous microspheres has become a feasible way to address existing problems. In this essay, we give a brief introduction of the porous microsphere, its characteristics, preparation methods, applications, and a brief summary of existing problems and research tendencies.
Topics: Animals; Drug Carriers; Humans; Microspheres; Particle Size; Polymerization; Porosity
PubMed: 23515359
DOI: 10.2147/IJN.S41271 -
Frontiers in Immunology 2022The versatility of natural killer cells has ignited growing interest in their therapeutic use for cancer and other immunotherapy treatments. However, NK cells compose a...
The versatility of natural killer cells has ignited growing interest in their therapeutic use for cancer and other immunotherapy treatments. However, NK cells compose a small portion of peripheral blood mononuclear cells (5%-20% of PBMCs) and clinical doses require billions of cells. Manufacturing suitable doses of NK cells remains a major challenge for NK immunotherapy. The current standard for expanding NK cells relies on feeder cells and fetal bovine serum to achieve large expansion, but both encounter regulatory concerns. We developed NK Cloudz, a dissolvable polymer-based microsphere platform, as an alternative to a feeder cell approach to expand NK cells. We demonstrated that a combination of NK Cloudz, a G-Rex6M culture vessel, and GMP Human Platelet Lysate expanded NK cells 387 ± 100-fold in 10 days from a PBMC starting population. The NK purity, viability, and cytotoxicity were similar to both a feeder cell protocol and an FBS-based protocol. Additionally, we found no significant differences between FBS and GMP Human Platelet Lysate and concluded that platelet lysate is a good xeno-free alternative to FBS for NK expansion. Overall, we demonstrated a feeder-cell-free and FBS-free protocol that leverages NK Cloudz as a promising step toward a commercial GMP manufacturing method to expand NK cells for therapeutic use.
Topics: Cell Proliferation; Feeder Cells; Humans; Killer Cells, Natural; Leukocytes, Mononuclear; Microspheres
PubMed: 35320938
DOI: 10.3389/fimmu.2022.803380 -
Scientific Reports Apr 2022In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La) with...
In osteoporosis and diabetes, it is essential to accelerate the bone repair and regeneration process. Trace rare earth elements such as lanthanum (La) ions (La) with appropriate concentrations are bioactive and can effectively regulate bone tissue performances. However, few well-established bone tissue engineering scaffolds can precisely and stably release La to promote bone regeneration significantly. Based on the advantages of biodegradable microspheres and microsphere-based scaffolds for controlled drug release, we developed poly(lactide-co-glycolide) (PLGA)-based microsphere-based scaffolds as both three-dimensional (3D) porous scaffolds and La storage and release systems for osteogenesis. So far, there is no study about microsphere-based scaffolds to release trace La to induce osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). PLGA microspheres co-embedded with La-doped mesoporous silica (LMS) with different amounts of doped La were sintered to prepare the LMS/PLGA (LMSP) microsphere-based scaffold. The La release behavior of LMSP can be controlled by adjusting the doping amount of La in mesoporous silica (MS). All these scaffolds possessed a 3D network architecture. With the increase of La doping, LMSP can better compensate for the pH decrease caused by PLGA degradation. The combination of MS and PLGA can avoid the cytotoxicity of MS alone. All prepared LMSP scaffolds were non-cytotoxic. After BMSCs were implanted on scaffolds, LMSP could promote cells adhesion, proliferation, and osteogenic differentiation. Among these microsphere-based scaffolds, LMSP-3 with stable and higher dose La release behavior showed the strongest ability to enhance the osteogenesis of BMSCs. The results showed that microsphere-based scaffolds with the ability to store and stably control the release of La could effectively improve osteogenic performance, which provides a new idea for the construction of bone tissue engineering scaffolds.
Topics: Bone Regeneration; Microspheres; Osteogenesis; Polylactic Acid-Polyglycolic Acid Copolymer; Silicon Dioxide; Tissue Engineering; Tissue Scaffolds
PubMed: 35430599
DOI: 10.1038/s41598-022-10347-0 -
Biophysical Journal Jun 2021Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak...
Many biologically important cell binding processes, such as the rolling of leukocytes in the vasculature, are multivalent, being mediated by large numbers of weak binding ligands. Quantitative agreement between experiments and models of rolling has been elusive and often limited by the poor understanding of the binding and unbinding kinetics of the ligands involved. Here, we present a cell-free experimental model for such rolling, consisting of polymer microspheres whose adhesion to a glass surface is mediated by ligands with well-understood force-dependent binding free energy-short complementary DNA strands. We observe robust rolling activity for certain values of the shear rate and the grafted DNA strands' binding free energy and force sensitivity. The simulation framework developed to model leukocyte rolling, adhesive dynamics, quantitatively captures the mean rolling velocity and lateral diffusivity of the experimental particles using known values of the experimental parameters. Moreover, our model captures the velocity variations seen within the trajectories of single particles. Particle-to-particle variations can be attributed to small, plausible differences in particle characteristics. Overall, our findings confirm that state-of-the-art adhesive dynamics simulations are able to capture the complex physics of particle rolling, boding well for their extension to modeling more complex systems of rolling cells.
Topics: Adhesives; Cell Adhesion; DNA; Leukocyte Rolling; Leukocytes; Microspheres
PubMed: 33838138
DOI: 10.1016/j.bpj.2021.03.038 -
Experimental Biology and Medicine... Oct 2022Microsphere-based flow cytometry is a highly sensitive emerging technology for specific detection and clinical analysis of antigens, antibodies, and nucleic acids of... (Review)
Review
Microsphere-based flow cytometry is a highly sensitive emerging technology for specific detection and clinical analysis of antigens, antibodies, and nucleic acids of interest. In this review, studies that focused on the application of flow cytometry as a viable alternative for the investigation of infectious diseases were analyzed. Many of the studies involve research aimed at epidemiological surveillance, vaccine candidates and early diagnosis, non-infectious diseases, specifically cancer, and emphasize the simultaneous detection of biomarkers for early diagnosis, with accurate results in a non-invasive approach. The possibility of carrying out multiplexed assays affords this technique high versatility and performance, which is evidenced in a series of clinical studies that have verified the ability to detect several molecules in low concentrations and with minimal sample volume. As such, we demonstrate that microsphere-based flow cytometry presents itself as a promising technique that can be adopted as a fundamental element in the development of new diagnostic methods for a number of diseases.
Topics: Humans; Flow Cytometry; Microspheres; Antigens; Biomarkers; Communicable Diseases
PubMed: 35974694
DOI: 10.1177/15353702221113856 -
Drug Discoveries & Therapeutics Jul 2023The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations.... (Review)
Review
The use of harmful solvents during the preparation of pharmaceutical formulations is restricted to preserve environment and ensure safety of industrial operations. However, harmful solvents must be used to produce certain formulations. For instance, methylene chloride has been used in the fabrication of polylactic acid (PLA) and poly(lactic-co-glycolic) acid (PLGA) microspheres. This review highlights the latest advances in the strategy of PLA or PLGA microsphere production from non-halogenated solvents and describes advantages and limitations of these methods. The study also discusses the development of dry fabrication techniques for microsphere fabrication and the positioning of conventional and dry fabrication in the containment concept for workers' safety.
Topics: Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Polyglycolic Acid; Lactic Acid; Microspheres; Polyesters; Solvents; Particle Size
PubMed: 37245983
DOI: 10.5582/ddt.2023.01008 -
PloS One 2022Hydrophilic materials immersed in aqueous solutions show near-surface zones that exclude suspended colloids and dissolved molecules. These exclusion zones (EZs) can...
Hydrophilic materials immersed in aqueous solutions show near-surface zones that exclude suspended colloids and dissolved molecules. These exclusion zones (EZs) can extend for tens to hundreds of micrometers from hydrophilic surfaces and show physicochemical properties that differ from bulk water. Here we report that exposure of standard aqueous microsphere suspensions to static magnetic fields creates similar microsphere-free zones adjacent to magnetic poles. The EZs build next to both north and south poles; and they build whether the microspheres are of polystyrene or carboxylate composition. EZ formation is accompanied by ordered motions of microspheres, creating dense zones some distance from the magnetic poles and leaving microsphere-free zones adjacent to the magnet. EZ size was larger next to the north pole than the south pole. The difference was statistically significant when polystyrene microspheres were used, although not when carboxylate microspheres were used. In many ways, including both size and dynamics, these exclusion zones resemble those found earlier next to various hydrophilic surfaces. The ability to create EZs represents a feature of magnets not previously revealed.
Topics: Hydrophobic and Hydrophilic Interactions; Magnetic Fields; Microspheres; Polystyrenes; Water
PubMed: 35622780
DOI: 10.1371/journal.pone.0268747 -
Journal of Biomedical Materials... Feb 2022Fast acting topical hemostatic agents play a key role in hemorrhage control. Retarding fibrinolysis is also critical in improving coagulation, thereby expanding chances...
Fast acting topical hemostatic agents play a key role in hemorrhage control. Retarding fibrinolysis is also critical in improving coagulation, thereby expanding chances of survival. The purpose of the present work was to investigate the physical properties, loading capacity and hemostatic efficacy of newly developed nanoclay microsphere frameworks (NMFs) loaded with tranexamic acid (TA), as antifibrinolytic agent. Nanoclay compositions were prepared with increasing levels of TA. Results showed that TA was successfully incorporated into the nanoclay structure and released when solvated with ethanol. Both doped and undoped NMFs significantly decreased activated partial thromboplastin time and increased clot stiffness, which was attributed to significantly thinner fibrin fibers and a denser clot structure.
Topics: Fibrinolysis; Hemostasis; Hemostatics; Microspheres; Tranexamic Acid
PubMed: 34288380
DOI: 10.1002/jbm.b.34918