Dextran Microspheres Research Articles

Rational Design of Liquid-Liquid Microdispersion Droplet Microreactors for the Controllable Synthesis of Highly Uniform and Monodispersed Dextran Microspheres.

Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 μm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.

Synthesis of eco-friendly multifunctional dextran microbeads for multiplexed assays

There has been an increasing demand for simultaneous detection of multiple analytes in one sample. Microbead-based platforms have been developed for multiplexed assays. However, most of the microbeads are made of non-biodegradable synthetic polymers, leading to environmental and human health concerns. In this study, we developed an environmentally friendly dextran microbeads as a new type of multi-analyte assay platform. Biodegradable dextran was utilized as the primary material. Highly uniform magnetic dextran microspheres were successfully synthesized using the Shirasu porous glass (SPG) membrane emulsification technique. To enhance the amount of surface functional groups for ligand conjugation, we coated the dextran microbeads with a layer of dendrimers via a simple electrostatic adsorption process. Subsequently, a unique and efficient click chemistry coupling technique was developed for the fluorescence encoding of the microspheres, enabling multiplexed detection. The dextran microbeads were tested for 3-plex cytokine analysis, and exhibited excellent biocompatibility, stable coding signals, low background noise and high sensitivity.

High drug loading hydrophobic cross-linked dextran microspheres as novel drug delivery systems for the treatment of osteoarthritis

Drug delivery via intra-articular (IA) injection has proved to be effective in osteoarthritis (OA) therapy, limited by the drug efficiency and short retention time of the drug delivery systems (DDSs). Herein, a series of modified cross-linked dextran (Sephadex, S0) was fabricated by respectively grafting with linear alkyl chains, branched alkyl chains or aromatic chain, and acted as DDSs after ibuprofen (Ibu) loading for OA therapy. This DDSs expressed sustained drug release, excellent anti-inflammatory and chondroprotective effects both in IL-1β induced chondrocytes and OA joints. Specifically, the introduction of a longer hydrophobic chain, particularly an aromatic chain, distinctly improved the hydrophobicity of S0, increased Ibu loading efficiency, and further led to significantly improving OA therapeutic effects. Therefore, hydrophobic microspheres with greatly improved drug loading ratio and prolonged degradation rates show great potential to act as DDSs for OA therapy.

High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury

Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8–63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 μg) within the limited administration volume (10 μL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.

Changes in the Pulmonary Artery Wave Reflection in Dogs with Experimentally-Induced Acute Pulmonary Embolism and the Effect of Vasodilator

Simple SummaryPulmonary hypertension (PH) remains a fatal disease, despite the advances in disease-specific therapies. This may be because the assessment of pulmonary hemodynamics in PH has not been established. Recently, several studies have reported that the pulmonary arterial wave reflection (PAWR) might influence the right ventricular afterload and could provide additional information regarding the severity and progression of PH. However, the pathophysiology of PAWR has some unclear points particularly in the case of acute pulmonary embolism (APE). The objective of this study was to investigate, for the first time, the characteristics of PAWR in a dog model of APE using dual-tipped sensor wire. From the result of the present study, after dogs developed PH by injections of dextran microsphere, PAWR was increased significantly along with the pulmonary vascular resistance (PVR) and reduced after vasodilator administration. In addition, PAWR was significantly correlated with PVR and right ventricular fractional area of change (FAC). These results indicating that PAWR may be useful as a new evaluation method in PH and may detect changes related to right ventricular afterload earlier than pulmonary artery pressure (PAP).Pulmonary hypertension (PH) is a complex syndrome that has been frequently diagnosed in dogs and humans and can be detected by Doppler echocardiography and invasive catheterization. Recently, PAWR attracts much attention as a noninvasive approach for the early detection of PH. The present study aims to investigate the PAWR changes in acute pulmonary embolism (APE) and highlight the response of PAWR variables to vasodilator therapy in dogs. For this purpose, anesthesia and catheterization were performed in 6 Beagle dogs. After that, APE was experimentally conducted by Dextran microsphere administration, followed by vasodilator (Nitroprusside; 1μg/kg/min/IV) administration. The hemodynamics, echocardiography, PVR and PAWR variables were evaluated at the baseline, after APE and after administration of nitroprusside. The result showed a significant increase in PVR, PAP, tricuspid regurgitation (TR) as well as PAWR variables following APE induction compared with the baseline (p < 0.05). Vasodilation caused by administration of nitroprusside reduced the mean atrial pressure, PVR and PAWR parameters. There were a significant correlation and linear regression between PAWR indices and PVR as well as right ventricular function parameters. In conclusion, PAWR is not only correlated with PVR but also the right ventricular function parameter, which indicates that PAWR may be useful as a new evaluation method in PH, considering that PAWR can assess both right ventricular afterload and right ventricular function.

Hydrogel microspheres for spatiotemporally controlled delivery of RNA and silencing gene expression within scaffold-free tissue engineered constructs

Delivery systems for controlled release of RNA interference (RNAi) molecules, including small interfering (siRNA) and microRNA (miRNA), have the potential to direct stem cell differentiation for regenerative musculoskeletal applications. To date, localized RNA delivery platforms in this area have focused predominantly on bulk scaffold-based approaches, which can interfere with cell-cell interactions important for recapitulating some native musculoskeletal developmental and healing processes in tissue regeneration strategies. In contrast, scaffold-free, high density human mesenchymal stem cell (hMSC) aggregates may provide an avenue for creating a more biomimetic microenvironment. Here, photocrosslinkable dextran microspheres (MS) encapsulating siRNA-micelles were prepared via an aqueous emulsion method and incorporated within hMSC aggregates for localized and sustained delivery of bioactive siRNA. siRNA-micelles released from MS in a sustained fashion over the course of 28 days, and the released siRNA retained its ability to transfect cells for gene silencing. Incorporation of fluorescently labeled siRNA (siGLO)-laden MS within hMSC aggregates exhibited tunable siGLO delivery and uptake by stem cells. Incorporation of MS loaded with siRNA targeting green fluorescent protein (siGFP) within GFP-hMSC aggregates provided sustained presentation of siGFP within the constructs and prolonged GFP silencing for up to 15 days. This platform system enables sustained gene silencing within stem cell aggregates and thus shows great potential in tissue regeneration applications. Statement of SignificanceThis work presents a new strategy to deliver RNA-nanocomplexes from photocrosslinked dextran microspheres for tunable presentation of bioactive RNA. These microspheres were embedded within scaffold-free, human mesenchymal stem cell (hMSC) aggregates for sustained gene silencing within three-dimensional cell constructs while maintaining cell viability. Unlike exogenous delivery of RNA within culture medium that suffers from diffusion limitations and potential need for repeated transfections, this strategy provides local and sustained RNA presentation from the microspheres to cells in the constructs. This system has the potential to inhibit translation of hMSC differentiation antagonists and drive hMSC differentiation toward desired specific lineages, and is an important step in the engineering of high-density stem cell systems with incorporated instructive genetic cues for application in tissue regeneration.

The dry powder formulation of mixed cross-linked dextran microspheres and tetanus toxoid-loaded trimethyl chitosan nanospheres as a potent adjuvant for nasal delivery system.

Objective(s):The present study aimed to determine the immunoadjuvant efficacy of mixed cross-linked dextran microspheres (CDM) and tetanus toxoid (TT)-loaded trimethyl chitosan (TMC) nanospheres in dry powder form. Materials and Methods:The TMC nanoparticles (NPs) containing TT were produced using the ionic gelation method. Co-administration of TT-loaded TMC NPs and CDM as an absorption enhancer was performed to improve immunity against the antigen. Dry powder formulations were delivered via the nasal route in a rabbit model. Results:Among immunization groups, mixing of CDM with TT encapsulated in TMC NPs could elicit the highest titer of systemic IgG antibody. Furthermore, the addition of CDM to TT-loaded TMC enhanced the sIgA response relative to the TT solution. Conclusion:The TMC NPs had a considerable effect on mucosal and systemic immunity against the TT antigen. Therefore, the CDM excipient can be utilized for nasal immunization to elevate systemic and mucosal responses.

Human Histology and Persistence of Various Injectable Filler Substances for Soft Tissue Augmentation.

An increasing number of soft tissue filler substances have been introduced to the beauty market outside the U.S. which lackexperimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence. At 1, 3, 6, and 9 months the test sites were excised, histologically examined, and graded according to foreign body reactions classification. Collagen (Zyplast) was phagocytosed at 6 months and hyaluronic acid (Restylane) at 9 months. PMMA microspheres (Artecoll) had encapsulated with connective tissue, macrophages, and sporadic giant cells. Silicone oil (PMS 350) was clinically inconspicuous but dissipated into the tissue, causing a chronic foreign body reaction. Polylactic acid microspheres (New-Fill) induced a mild inflammatory response and had disappeared clinically at 4 months. Dextran microspheres (Reviderm intra) induced a pronounced foreign body reaction and had disappeared at 6 months. Polymethylacrylate particles (Dermalive) induced the lowest cellular reaction but had disappeared clinically at 6 months. Polyacrylamide (Aquamid) was well tolerated and remained palpable to a lessening degree over the entire testing period. Histologically, it dissipated more slowly and was kept in place through fine fibrous capsules. Polyvinylhydroxide microspheres suspended in acrylamide (Evolution) were well tolerated, slowly diminishing over 9 months. Calcium hydroxylapatite microspheres (Radiance FN) induced almost no foreign body reaction but were absorbed by the skin at 12 months.Host defense mechanisms react differently to the various filler materials, but all substances- resorbable or nonresorbable-appeared to be clinically and histologically safe, although all exhibit undesirable side effects. Since the mechanism of late inflammation or granuloma formation is still unknown, early histological findings are not useful in predicting possible late reactions to filler substances.

Hydrogel Microspheres for Spatiotemporally Controlled Delivery of Rna and Silencing Gene Expression within Scaffold-Free Tissue Engineered Constructs

Delivery systems for controlled release of RNA interference (RNAi) molecules, including small interfering (siRNA) and microRNA (miRNA), have the potential to direct stem cell differentiation for regenerative musculoskeletal applications. To date, localized RNA delivery platforms in this area have focused predominantly on bulk scaffold-based approaches, which can interfere with cell-cell interactions important for recapitulating some native musculoskeletal developmental and healing processes in tissue regeneration strategies. In contrast, scaffold-free, high density human mesenchymal stem cell (hMSC) condensations may provide an avenue for creating a more biomimetic microenvironment. Here, photocrosslinkable dextran microspheres (MS) encapsulating siRNA-micelles were prepared via an aqueous emulsion method and incorporated within hMSC aggregates for localized and sustained delivery of bioactive siRNA. siRNA-micelles released from MS in a sustained fashion over the course of 28 days, and the released siRNA retained its ability to transfect cells for gene silencing. Incorporation of fluorescently labeled siRNA (siGLO)-laden MS within hMSC aggregates exhibited tunable siGLO delivery and uptake by stem cells. Incorporation of MS loaded with siRNA targeting green fluorescent protein (siGFP) within GFP-hMSC aggregates provided sustained presentation of siGFP within the constructs and prolonged GFP silencing for up to 15 days. This platform system enables sustained gene silencing within stem cell condensations and thus shows great potential in tissue regeneration applications.

Neuroprotection: Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity (Adv. Mater. 14/2018)

New treatment strategies for spinal‐cord injury are being actively pursued. In article number 1706032, Helder A. Santos, Guoyong Yin, Jin Fan, and co‐workers show that intrathecally injected biodegradable polymeric microspheres, acetalated dextran, can protect traumatically injured spinal cord. The neuroprotective feature of acetalated dextran microspheres is achieved by sequestering the excessive glutamate and calcium ions in cerebrospinal fluid, and consequently attenuating the glutamateinduced excitotoxicity.

Hollow phosphorylcholine polymer vesicles prepared by a coaxial electrospray technique

Hollow vesicles composed of a phosphorylcholine polymer were prepared using a coaxial electrospray technique and an inorganic microstructured template. An aqueous solution containing calcium chloride and chitosan, and 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer ethanol solution were electrosprayed from coaxial double needles into a phosphate solution to obtain microparticles composed of calcium phosphate (CaP) and chitosan covered with MPC polymer, followed by the removal of CaP/chitosan template to produce novel hollow vesicles composed of MPC polymer. The resulting hollow vesicles had 300–400 μm in diameter. Investigation using fluorescently labeled MPC polymer revealed that the vesicle membrane was composed of MPC polymer. Model substances with relatively high molecular weights (dextran and polymeric microspheres) were readily encapsulated in the hollow vesicles. Microscopic observations of the mobility of encapsulated microspheres inside a hollow vesicle indicated the fluidity of its aqueous interior. Finally, we succeeded in the encapsulation and cultivation of living yeast cells within the vesicles, which demonstrates that this technique can encapsulate a physiologically active substance in the hollow vesicles and maintain its activity.

Immunoadjuvant potential of cross-linked dextran microspheres mixed with chitosan nanospheres encapsulated with tetanus toxoid

Context: Nasal mucosa is a desirable route for mucosal vaccine delivery. Mucosal co-administration of chitosan nanoparticles with absorption enhancers such as cross-linked dextran microspheres (CDM, Sephadex®) is a promising antigen delivery system. Objective: In the current study, the chitosan nanospheres loaded with tetanus toxoid (CHT:TT NPs) was prepared and characterized. The immune responses against tetanus toxoid after nasal administration of CHT:TT NPs alone or mixed with CDM were also determined. Materials and methods: Chitosan nanospheres were prepared by ionic gelation method. Particle size, releasing profile and antigen stability were evaluated by dynamic light scattering, diffusion chamber and SDS-PAGE methods, respectively. Rabbits were nasally immunized with different formulations loaded with 40 Lf TT. After three times immunizations with 2 weeks intervals, sera IgG titres and nasal lavage sIgA titres were determined. Results: Mean size of CHT NPs and CHT:TT NPs were 205 ± 42 nm and 432 ± 85 nm, respectively. The release profile showed that 42.4 ± 10.5% of TT was released after 30 min and reached to a steady state after 1.5 h. Stability of encapsulated TT in nanospheres was confirmed by SDS-PAGE. The antibody titres showed that CHT:TT NPs-induced antibody titres were higher than TT solution. CHT NPs mixed with CDM induced the systemic IgG and nasal lavage sIgA titres higher than intranasal administration of TT solution (p < 0.001). Discussion and conclusion: As the results indicated, these CHT:TT NPs when co-administered with CDM were able to induce more immune responses and have the potential to be used in mucosal immunization.

Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study

Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12min), high dosing frequency (1.4mg/m2 per week for 4weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-β-glycerophosphate gel (VCS-Dextran-MSs-Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8±2.4μm and −18.3±0.11mV along with the encapsulation efficiency of about 60.4±4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72h and 720h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology.

Preparation and drug controlled release of porous octyl-dextran microspheres

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

Free and copolymerized γ-cyclodextrins regulate the performance of dexamethasone-loaded dextran microspheres for bone regeneration.

Polymeric particles acting as sources of biological cues to promote tissue regeneration are currently an interesting topic in bone tissue engineering research. In this study, microspheres of dextran-methacrylate (dextran-MA) and γ-cyclodextrins (γ-CD) for the delivery of osteogenic agents were prepared by means of photopolymerization on biomimetic superhydrophobic surfaces. The effects of the incorporation of the γ-CD units as free entities or as structural monomers (acrylamidomethyl-γ-cyclodextrin, γ-CD-NMA) on dexamethasone loading and release performance were evaluated in detail in order to achieve osteogenic differentiation of human stem cells. The copolymerization of dextran-MA with γ-CD-NMA improved the loading capacity of the particles and also provided a sustained release of dexamethasone for several days. The biological studies revealed that such microspheres were cytocompatible and capable of inducing the differentiation of human adipose-derived stem cells (hASCs) to osteoblasts, as determined from an increase of alkaline phosphatase (ALP) activity between days 3 and 7. Such results were also confirmed using ALP staining. Therefore, immobilization of γ-CDs onto the dextran-MA network may be particularly useful for the development of cytocompatible implantable spherical biomaterials for bone tissue engineering purposes.

Biphasic release of protein from polyethylene glycol and polyethylene glycol/modified dextran microspheres

Dextrans show great promise for delivery of therapeutic agents. Dextran acetates (DAs) were synthesized with increasing degrees of substitution (DA1 < DA2 < DA3) by the reaction of the polysaccharide dextran (70 kDa) with acetic anhydride. A series of polyethylene glycol (PEG)/DA microspheres were prepared and tested with bovine serum albumin (BSA) functioning as a model protein. Particle size (0.74-0.85 μm) and encapsulation efficiency (56-70%) increased with the degree of substitution along with a slower release rate of protein from PEG/DA microspheres. Time to release 90% of protein rose from 31 to 118 min. Percentage of BSA released from PEG and PEG/DA3 microspheres with time (min) was modeled mathematically [Y(PEG) = 100(1 - e(-0.12t)); Y(PEG/DA3) = 100(1 - e(-0.024t))] to predict cumulative delivery from mixtures in vitro over a period of hours when constrained to a target level at 30 min. The system is examined for potential application in thrombolytic therapy.

Effective parameters in determining cross-linked dextran microsphere characteristics: screening by Plackett–Burman design-of-experiments

This study aims to screen the effective parameters in preparing cross-linked dextran microspheres (CDMs) to make them controllable for obtaining microspheres with tunable properties. Microspheres were prepared by chemical crosslinking of dextran dissolved in internal phase of an inverse emulsion system (W/O) using epichlorohydrin (ECH). A Plackett–Burman design-of-experiments was employed as the screening methodology to investigate the effects of the kinetics and process parameters, i.e. the mixing speed and emulsification time on the resulting microsphere characteristics. Crosslinking reaction temperature and concentrations of the emulsion constituents including dextran, ECH and sodium hydroxide were the studied kinetic parameters. Equilibrium swelling ratio, mean particle size and size distribution of the resulting CDMs were measured and statistically analysed. It was found that dextran concentration is the most influential parameter on the particle size and swelling ratio of the obtained CDMs. Increasing dextran concentration in the aqueous phase leads to a significant increase in the mean particle size and decrement in water uptake capacity of the resulting microspheres, respectively.

Full factorial design‐of‐experiments for preparation of crosslinked dextran microspheres

AbstractThis work describes full factorial design‐of‐experiment methodology for exploration of effective parameters on physical properties of dextran microspheres prepared via an inverse emulsion (W/O) technique. Microspheres were prepared by chemical crosslinking of dextran dissolved in internal phase of the emulsion using epichlorohydrin. The input parameters were dextran concentration in the aqueous phase, crosslinking ratio, and concentrations of sodium hydroxide and span 80 as the reaction catalyst and surfactant, respectively. Chemical structure of the resulting microspheres was analyzed spectroscopically using Fourier‐transform infrared technique. Final decomposition temperature, mean particle size and its distribution and equilibrium swelling ratio were selected as output responses. Microspheres with smooth surface were obtained according to scanning electron micrographs. It was found that an increase in dextran concentration in the aqueous internal phase increases mean particle diameter of the resulting microspheres, significantly. Moreover, water uptake capacity for the microspheres was dependent on both the dextran concentration and crosslinking ratio. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013