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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 -
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 -
International Journal of Molecular... Apr 2023Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various... (Review)
Review
Tissue injury, one of the most common traumatic injuries in daily life, easily leads to secondary wound infections. To promote wound healing and reduce scarring, various kinds of wound dressings, such as gauze, bandages, sponges, patches, and microspheres, have been developed for wound healing. Among them, microsphere-based tissue dressings have attracted increasing attention due to the advantage of easy to fabricate, excellent physicochemical performance and superior drug release ability. In this review, we first introduced the common methods for microspheres preparation, such as emulsification-solvent method, electrospray method, microfluidic technology as well as phase separation methods. Next, we summarized the common biomaterials for the fabrication of the microspheres including natural polymers and synthetic polymers. Then, we presented the application of the various microspheres from different processing methods in wound healing and other applications. Finally, we analyzed the limitations and discussed the future development direction of microspheres in the future.
Topics: Humans; Microspheres; Wound Healing; Cicatrix; Polymers; Biocompatible Materials
PubMed: 37108482
DOI: 10.3390/ijms24087319 -
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 -
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 -
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 -
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 -
Acta Biomaterialia Mar 2023Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute...
Effective antigen delivery facilitates antiviral vaccine success defined by effective immune protective responses against viral exposures. To improve severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen delivery, a controlled biodegradable, stable, biocompatible, and nontoxic polymeric microsphere system was developed for chemically inactivated viral proteins. SARS-CoV-2 proteins encapsulated in polymeric microspheres induced robust antiviral immunity. The viral antigen-loaded microsphere system can preclude the need for repeat administrations, highlighting its potential as an effective vaccine. STATEMENT OF SIGNIFICANCE: Successful SARS-CoV-2 vaccines were developed and quickly approved by the US Food and Drug Administration (FDA). However, each of the vaccines requires boosting as new variants arise. We posit that injectable biodegradable polymers represent a means for the sustained release of emerging viral antigens. The approach offers a means to reduce immunization frequency by predicting viral genomic variability. This strategy could lead to longer-lasting antiviral protective immunity. The current proof-of-concept multipolymer study for SARS-CoV-2 achieve these metrics.
Topics: Humans; SARS-CoV-2; COVID-19 Vaccines; Microspheres; COVID-19; Vaccines; Antiviral Agents
PubMed: 36581007
DOI: 10.1016/j.actbio.2022.12.043