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Expert Opinion on Drug Delivery 2016This review discusses advances in the field of microsphere testing. (Review)
Review
INTRODUCTION
This review discusses advances in the field of microsphere testing.
AREAS COVERED
In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties.
EXPERT OPINION
Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.
Topics: Drug Carriers; Drug Liberation; Drug Stability; Humans; Microspheres; Particle Size; Pharmaceutical Preparations
PubMed: 26828874
DOI: 10.1517/17425247.2016.1134484 -
Current Protocols Dec 2021The ability of stem cells to differentiate into specialized cells make them a valuable tool for therapeutic applications. 3D bioprinting, a subset of additive...
The ability of stem cells to differentiate into specialized cells make them a valuable tool for therapeutic applications. 3D bioprinting, a subset of additive manufacturing, uses bioinks composed of cells and biomaterials to create living tissues. The use of bioactive factors like small molecules and proteins can promote stem cell differentiation into the desired cell phenotypes for tissue regeneration. Small molecules can accelerate the process of regeneration in tissue engineering, maintain bioactivity in a biological environment, and minimize the costs associated with this process. Additionally, they can be encapsulated in specialized drug-delivery devices called microspheres for controlled release. Microspheres are small (1-1000 μm) spherical particles usually made from biodegradable and biocompatible polymers that can be loaded with drugs and other bioactive components. They can then be integrated into stem-cell-laden bioinks used to form bioprinted tissues, where they will release the encapsulated drug and promote differentiation of stem cells into the desired mature cell type. Microspheres can be widely used to encapsulate a broad range of therapeutic agents, including hydrophilic and hydrophobic small molecule drugs, DNA, and proteins. The release of encapsulated molecules occurs through degradation and erosion of the polymer matrix. This article provides detailed protocols for fabricating and sterilizing drug-releasing microspheres made from poly-ε-caprolactone, a promising biodegradable polymer often used for controlled drug delivery due to its biocompatibility and biodegradation kinetics. Additional protocols describe characterization of the loading and size of microspheres as well as incorporation of microspheres into a fibrin-based bioink for 3D bioprinting. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Fabrication of drug-releasing PCL microspheres Support Protocol 1: Preparation of microspheres for determination of encapsulation efficiency by HPLC Support Protocol 2: Preparation of microspheres for SEM analysis Basic Protocol 2: Incorporation of microspheres into fibrin-based bioink.
Topics: Cell Differentiation; Microspheres; Pharmaceutical Preparations
PubMed: 34919351
DOI: 10.1002/cpz1.331 -
Molecules (Basel, Switzerland) Dec 2023In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer ((BMA--DAMA--MMA)) solution were...
In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer ((BMA--DAMA--MMA)) solution were introduced into the device for the preparation of hydrogel fibers loaded with polymer microspheres. The structure of the microsphere fiber, including the size and spacing of the microspheres, could be controlled by flow rate, and the microspheres were able to degrade and release cargo responding to acidic pH conditions. By modification with carboxymethylcellulose (CMC), alginate hydrogel exhibited enhanced pH sensitivity (shrunk in acidic while swollen in basic condition). This led to an impact on the diffusion rate of the molecules released from the inner microspheres. The microsphere fiber showed dramatic and negligible degradation and drug release in tumor cell (i.e., A431 and A549 cells) and normal cell environments, respectively. These results indicated that the microsphere fiber prepared in this study showed selective drug release in acidic environments, such as tumor and inflammation sites, which could be applied as a smart surgical dressing with normal tissue protective properties.
Topics: Drug Liberation; Microfluidics; Microspheres; Alginates; Hydrogels; Polymers; Hydrogen-Ion Concentration
PubMed: 38202775
DOI: 10.3390/molecules29010193 -
The Chinese Journal of Dental Research Mar 2022Microspheres have been widely utilised as versatile carriers in biomedical applications. In recent years, as a new type of injectable scaffold, microspheres have...
Microspheres have been widely utilised as versatile carriers in biomedical applications. In recent years, as a new type of injectable scaffold, microspheres have attracted increasing attention in the field of regenerative medicine owing to their various advantages including their small size, large specific surface area and mimicry of the 3D native environment. These characteristics enable them to adopt the narrow and irregular anatomy of the tooth and become an ideal scaffold for endodontic regeneration. Microspheres play an important role in carrying biologics (cells, biomolecules and drugs), which effectively regulate the fate of stem cells and control the release of growth factors and drugs. Cell-laden microspheres, which can be divided into microcarriers and microcapsules, have great application prospects in dental pulp regeneration. This paper summarises the properties and characteristics of microsphere scaffolds used in tissue engineering, placing emphasis on their advantages and applications in endodontic regeneration.
Topics: Dental Pulp; Microspheres; Regeneration; Regenerative Medicine; Tissue Engineering
PubMed: 35293708
DOI: 10.3290/j.cjdr.b2752709 -
Drug Delivery and Translational Research Apr 2023Microspheres have gained much attention from pharmaceutical and medical industry due to the excellent biodegradable and long controlled-release characteristics. However,...
Microspheres have gained much attention from pharmaceutical and medical industry due to the excellent biodegradable and long controlled-release characteristics. However, the drug release behavior of microspheres is influenced by complicated formulation and manufacturing factors. The traditional formulation development of microspheres is intractable and inefficient by the experimentally trial-and-error methods. This research aims to build a prediction model to accelerate microspheres product development for small-molecule drugs by machine learning (ML) techniques. Two hundred eighty-six microsphere formulations with small-molecule drugs were collected from the publications and pharmaceutical company, including the dissolution temperature at both 37 ℃ and 45 ℃. After the comparison of fourteen ML approaches, the consensus model achieved accurate predictions for the validation set at 37 ℃ and 45 ℃ (R = 0.880 vs. R = 0.958), indicating the good performance to predict the in vitro drug release profiles at both 37 ℃ and 45 ℃. Meanwhile, the models revealed the feature importance of formulations, which offered meaningful insights to the microspheres development. Experiments of microsphere formulations further validated the accuracy of the consensus model. Furthermore, molecular dynamics (MD) simulation provided a microscopic view of the preparation process of microspheres. In conclusion, the prediction model of microsphere formulations for small-molecule drugs was successfully built with high accuracy, which is able to accelerate microspheres product development and promote the quality control of microspheres for the pharmaceutical industry.
Topics: Delayed-Action Preparations; Microspheres; Drug Liberation; Particle Size
PubMed: 36454434
DOI: 10.1007/s13346-022-01253-z -
Recent Patents on Nanotechnology 2017This review focuses on the fundamental fluid mechanics which governs the generation of micro/nanospheres. The micro/nanosphere generation process has gathered... (Review)
Review
This review focuses on the fundamental fluid mechanics which governs the generation of micro/nanospheres. The micro/nanosphere generation process has gathered significant attention in the past two decades, since micro/nanospheres are widely used in drug delivery, food science, cosmetics, and other application areas. Many methods have been developed based on different operating principles, such as microfluidic methods, electrospray methods, chemical methods, and so forth. This paper focuses on microfluidic methods. Although the structure of the microfluidic devices may be different, the operating principles behind them are often very similar. Following an initial discussion of the fluid mechanics related to the generation of microspheres, various design approaches are discussed, including T-junction, flow focusing, membrane emulsification, modified T-junction, and double emulsification methods. The advantages and problems associated with each method are also discussed. Next, the most commonly used computational fluid dynamics (CFD) methods are reviewed at three different levels: microscopic, mesoscopic, and macroscopic. Finally, the issues identified in the current literature are discussed, and some suggestions are offered regarding the future direction of technology development related to micro/nanosphere generation. Few relevant patents to the topic have been reviewed and cited.
Topics: Hydrodynamics; Membranes, Artificial; Microfluidic Analytical Techniques; Microspheres; Models, Theoretical; Nanospheres; Patents as Topic; Surface Tension
PubMed: 27562806
DOI: 10.2174/1872210510666160530125646 -
Bio Systems May 2023Proteinoids, or thermal proteins, are inorganic entities formed by heating amino acids to their melting point and commencing polymerisation to form polymeric chains....
Proteinoids, or thermal proteins, are inorganic entities formed by heating amino acids to their melting point and commencing polymerisation to form polymeric chains. Typically, their diameters range from 1μm to 10μm. Some amino acids incorporated into proteinoid chains are more hydrophobic than others, leading proteinoids to cluster together when they are present in aqueous solutions at specific concentrations, allowing them to grow into microspheres. The peculiar structure of proteinoids composed of linked amino acids endows them with unique properties, including action-potential like spiking of electrical potential. These unique properties make ensembles of proteinoid microspheres a promising substrate for designing future artificial brains and unconventional computing devices. To evaluate a potential of proteinoid microspheres for unconventional electronic devices we measure and analyse the data-transfer capacities of proteinoid microspheres. In experimental laboratory conditions we demonstrate that the transfer function of proteinoids microspheres is a nontrivial phenomenon, which might be due to the wide range of proteinoid shapes, sizes, and structures.
Topics: Microspheres; Proteins; Amino Acids
PubMed: 37076037
DOI: 10.1016/j.biosystems.2023.104892 -
Journal of Colloid and Interface Science Jan 2022Lipase is the most widely used enzyme in industry. Due to its unique "lid" structure, lipase can only show high activity at the oil-water interface, which means that...
Lipase is the most widely used enzyme in industry. Due to its unique "lid" structure, lipase can only show high activity at the oil-water interface, which means that water is needed in the catalytic esterification process. However, the traditional lipase catalytic system cannot effectively control "micro-water" in the esterification environment, resulting in the high content of free water, which hinders the esterification reaction and reduces the yield. In this paper, a promising strategy of esterification catalyzed by polyacrylamide hydrogel immobilized lipase is reported. The porous polyacrylamide hydrogel microspheres (PHM) prepared by inverse emulsion polymerization are used as carrier to adsorb lipase by hydrogen bonding interaction. These hydrogel microspheres provide a "micro-water environment" for lipase in the anhydrous reaction system, and further provide an oil-water interface for "interface activation" of lipase. The obtained lipase-porous polyacrylamide hydrogel microspheres (L-PHMs) exhibit higher temperature and pH stability compared with free lipase, and the optimum enzymatic activity reach 1350 U/g (pH 6, 40 °C). L-PHMs can still remain about 49% of their original activity after 20 reuses. Furthermore, L-PHMs have been successfully applied to catalyze the synthesis of conjugated linoleic acid ethyl ester. The results suggest that this immobilization method opens up a new way for the application of lipase in ester synthesis.
Topics: Enzymes, Immobilized; Esterification; Hydrogels; Hydrogen; Lipase; Microspheres
PubMed: 34492461
DOI: 10.1016/j.jcis.2021.08.147 -
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi =... Aug 2023Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage... (Review)
Review
Sodium alginate (SA) is a kind of natural polymer material extracted from kelp, which has excellent biocompatibility, non-toxicity, biodegradability and abundant storage capacity. The formation condition of sodium alginate gel is mild, effectively avoiding the inactivation of active substances. After a variety of preparation methods, sodium alginate microspheres are widely used in the fields of biomaterials and tissue engineering. This paper reviewed the common methods of preparing alginate microspheres, including extrusion, emulsification, electrostatic spraying, spray drying and coaxial airflow, and discussed their applications in biomedical fields such as bone repair, hemostasis and drug delivery.
Topics: Alginates; Biocompatible Materials; Drug Delivery Systems; Microspheres; Plastic Surgery Procedures
PubMed: 37666771
DOI: 10.7507/1001-5515.202211048 -
ACS Applied Bio Materials Feb 2022Three-dimensional cellular constructs derived from pluripotent stem cells allow the study of neurodevelopment and neurological disease within a spatially organized...
Three-dimensional cellular constructs derived from pluripotent stem cells allow the study of neurodevelopment and neurological disease within a spatially organized model. However, the robustness and utility of three-dimensional models is impacted by tissue self-organization, size limitations, nutrient supply, and heterogeneity. In this work, we have utilized the principles of nanoarchitectonics to create a multifunctional polymer/bioceramic composite microsphere system for stem cell culture and differentiation in a chemically defined microenvironment. Microspheres could be customized to produce three-dimensional structures of defined size (ranging from >100 to <350 μm) with lower mechanical properties compared with a thin film. Furthermore, the microspheres softened in solution, approaching more tissue-like mechanical properties over time. With neural stem cells (NSCs) derived from human induced pluripotent stem cells, microsphere-cultured NSCs were able to utilize multiple substrates to promote cell adhesion and proliferation. Prolonged culture of NSC-bound microspheres under differentiating conditions allowed the formation of both neural and glial cell types from control and patient-derived stem cell models. Human NSCs and differentiated neurons could also be cocultured with astrocytes and human umbilical vein endothelial cells, demonstrating application for tissue-engineered modeling of development and human disease. We further demonstrated that microspheres allow the loading and sustained release of multiple recombinant proteins to support cellular maintenance and differentiation. While previous work has principally utilized self-organizing models or protein-rich hydrogels for neural culture, the three-dimensional matrix developed here through nanoarchitectonics represents a chemically defined and robust alternative for the study of neurodevelopment and nervous system disorders.
Topics: Endothelial Cells; Humans; Induced Pluripotent Stem Cells; Microspheres; Nervous System Diseases; Neural Stem Cells
PubMed: 35045249
DOI: 10.1021/acsabm.1c01012