Gel Microspheres Research Articles

DEVELOPMENT AND CHARACTERIZATION OF MUCOADHESIVE MICROSPHERE-LOADED INTRANASAL GEL OF VENLAFAXINE HYDROCHLORIDE

ABSTRACTObjective: The main objective of the present work is to develop and characterize a novel mucoadhesive intranasal microsphere gel formulation ofdrug venlafaxine to control the drug release through nasal mucosa and reach the target site with minimal side effect. The objectives of the studyare (1) formulation of mucoadhesive microspheres, (2) evaluation of mucoadhesive microspheres, (3) formulation of mucoadhesive microsphereloadednasal gel, (4) and evaluation of nasal gel.Methods: Preparation of chitosan microsphere: The chitosan microspheres were prepared by emulsion cross-linking method. Preparation ofmicrosphere-loaded gel: The nasal gels with varying concentrations of Carbopol 934P were prepared by dispersing required quantity of Carbopol inrequired quantity of distilled water with continuous stirring and kept overnight for complete hydration. The gel was then modified by the addition ofvarying proportion of hydroxypropyl methylcellulose (HPMC) K4M.Results: The prepared microspheres were evaluated for size distribution, surface morphology by scanning electron microscopy, entrapment efficiency,compatibility by Fourier transform infrared spectroscopy, and differential scanning calorimetry. Entrapment efficiency of all formulations was foundmore than 70%. Microsphere formulation containing drug and polymer in the ratio of 1:2.5 was found to be optimized. Optimized microsphereformulation was then incorporated in gel prepared using Carbopol 934P and HPMC. Prepared gel formulations were studied for viscosity, spreadability,and in-vitro drug release in simulated nasal conditions. Viscosity of the optimized batch of gel was recorded at 1056 centipoise. Drug release wasprolonged for the microsphere-in-gel formulations compared to the microspheres alone. For the optimized batch of gel, cumulative drug release of85.67% was found after 8 hrs.Conclusion: The results suggest that venlafaxine hydrochloride mucoadhesive microsphere-loaded nasal gel would give sustained drug release andsuperior bioavailability in the brain sites.Keywords: Venlafaxine, Chitosan, Mucoadhesive, Microsphere, Nasal gel.

Growth adaptation of probiotics in biopolymer-based coacervate structures to enhance cell viability

The effect of inoculum size and growth of probiotic cells inside biopolymer-based coacervate structures, made from whey protein isolate and gum arabic, and a dual encapsulation method of complex coacervation coupled with ionotropic gelation on the survival of probiotics was evaluated under adverse environmental conditions; i.e. low pH, heating, and simulated gastric juice (SGJ). The encapsulated bacteria metabolized nutrients and multiplied within the coacervate structural assemblies, pointing to a rather open carrier-delivery system for microbial cells, allowing the exchange of metabolites and nutrients with the bulk liquid medium. Encapsulation of probiotic cells at low counts and subsequent growth improved cell viability upon heating or exposure to SGJ. When cells entrapped in complex coacervates were subsequently embedded in Ca2+-alginate gel microspheres, the remaining viable counts at pH 2.0 for 3 h were even higher by almost 1 logCFU/g. Overall, an initial low inoculum size of bacteria in complex coacervates, followed by culture growth (adaptation stage) and subsequent entrapment in alginate microspheres greatly enhanced the cell viability of probiotic cultures.

Preparation of crosslinked poly (acryloyloxyethyltrimethyl ammonium chloride) microsphere and its adsorption and mechanism towards shikimic acid

Shikimic acid (SA) is a key raw material for the synthesis of the antiviral drug, but its extraction and separation from plants is still limited. Crosslinked poly (acryloyloxyethyltrimethyl ammonium chloride, DAC) microspheres were synthesized via inverse-phase suspension polymerization. In the synthesizing, N,N′-methylene bisacrylamide (MBA) was used as crosslinker, cyclohexane as dispersed medium and span-60 as dispersants, obtaining CPDAC gel microspheres. The effect of polymerization condition on balling performance and the characteristics of CPDAC were examined. The adsorption properties of CPDAC towards SA were mainly explored and the data of adsorption isotherm were analyzed by using Langmuir, Freundlich, Temkin, Sips and Toth models. Furthermore, the adsorption mechanism was analyzed in depth, and the adsorption thermodynamics was also investigated. The results show that in order to prepare CPDAC, water phase must be added dropwise to oil phase, and the volume ratio of oil-water is more than 2:1. The mean diameter of CPDAC decreases with increasing span-60 and accelerating agitating rate. The strong electrostatic interaction is formed between quaternary ammonium nitrogen of CPDAC and COO– of SA. The adsorption kinetic data is fitted well with pseudo-first-order model. The adsorption ability is higher in aqueous water than ethanol, reaching 108mg/g, and Toth model is more suitable for describing the actual adsorption process. The adsorption of CPDAC towards SA is dependent on the pH value of the medium. The adsorption process is exothermic, the adsorption amount decreases with the increase of temperature, and the process is driven by enthalpy. The adsorption amount decreases with the increase of salinity. The reusability of CPDAC towards SA can keep 86.1% at the sixth cycle.

Production of monodisperse silica gel microspheres for bioencapsulation by extrusion into an oil cross-flow

Silica gel microspheres are ideal materials for bioencapsulation due to their mechanical properties, biocompatibility, and stability. Encapsulated cells are isolated from the environment and protected from predators, changes in pH, and osmotic stress. However methods for the production of silica gel microspheres suitable for bioencapsulation are not well established. This paper describes a method for the production of monodisperse silicon alkoxide cross-linked silica nanoparticle (SNP) gel microspheres for bioencapsulation in which silica gel precursor is extruded from a needle into a cross-flowing stream of mineral oil. Microspheres produced ranged from 1.3 to 2.9 mm in diameter with coefficients of variation ranging from 2 to 6%. Microsphere size was mainly controlled by the flowrate of the cross-flowing oil and smaller microspheres generally had larger coefficients of variation. The method described in this paper can be optimised to produce silica gel microspheres with a diverse range of compositions and properties.

Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin

Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms.

The Fabrication of ZrO2–ZrC Microspheres by Internal Gelation and Carbothermal Reduction Process

ZrO2–ZrC (ZrCO) ceramic microspheres were fabricated by combination of internal gelation and carbothermal reduction process. The internal gelation broth containing carbon powders was prepared and stored at room temperature of 25°C to form a precursor of microspheres. By dropping droplets of the broth into hot silicone, the gel microspheres would solidify within a few seconds by decomposition of hexamethylenetetramine (HMTA). The dispersability of the carbon powders in the broth is the key factor to producing ZrCO microspheres with uniform density distribution, as zirconium carbides are generated by the direct reduction of ZrO2 with carbon. The ZrCO ceramic microspheres fabricated with various mass ratio of ZrO2 and ZrC have good sphericity and no cracks through optimizing washing and heat treatment process.

Immobilization of Cyclooxygenase-2 on Silica Gel Microspheres: Optimization and Characterization.

In this study, immobilized COX-2 was successfully constructed through glutaraldehyde-mediated covalent coupling on functional silica gel microspheres. The optimum conditions, properties, and morphological characteristics of the immobilized COX-2 were investigated. The optimal immobilization process was as follows: about 0.02 g of aminated silica gel microspheres was activated by 0.25% GA solution for 6 h and mixed with 5 U of free recombinant COX-2 solution. Then, the mixture was shaken for 8 h at 20 °C. Results showed that the immobilized COX-2 produced by this method exhibited excellent biocatalytic activity, equivalent to that of free COX-2 under the test conditions employed. The best biocatalytic activity of immobilized COX-2 appeared at pH 8.0 and still maintained at about 84% (RSD < 7.39%, n = 3) at pH 10.0. For temperature tolerance, immobilized COX-2 exhibited its maximum biocatalytic activity at 40 °C and about 68% (RSD < 6.99%, n = 3) of the activity was maintained at 60 °C. The immobilized COX-2 retained over 85% (RSD < 7.26%, n = 3) of its initial biocatalytic activity after five cycles, and after 10 days storage, the catalytic activity of immobilized COX-2 still maintained at about 95% (RSD < 3.08%, n = 3). These characteristics ensured the convenient use of the immobilized COX-2 and reduced its production cost.

Mechanism for formation of Hollow and Granular Silica Aerogel Microspheres from rice husk ash for drug delivery

The present work describes a method for preparation of Hollow Silica Aerogel Microspheres (HSAMs) and Granular Silica Aerogel Microparticles (GSAMs) for drug delivery, from rice husk ash (RHA), an inexpensive source of biocompatible silica. This method involves a two-step sol–gel process for preparation of wet gel microspheres using an improved sol–gel/mineral-oil emulsion (containing dual surfactants), followed by solvent exchange and aging in aqueous ethanol, to replace water in the microspheres with ethanol. It is shown that the amount and concentration of the ammonium hydroxide (NH4OH) solution added during gelation process determine if hollow or granular wet gel particles form. A mechanism for the formation of HSAMs or GSAMs is proposed and validated by experiments. The wet gel particles are subsequently dried with supercritical carbon dioxide at 150bar and 50°C to obtain HSAMs or GSAMs. HSAMs afford high loading of drugs as illustrated by loading of 0.47g ibuprofen per g of HSAM. Further, a fast release of ibuprofen from loaded HSAMs compared to pure crystalline ibuprofen and other loaded forms, indicates that HSAMs produced by the present method are good drug delivery vehicles.

Synthesis of polyglycolic acid grafting from sodium alginate through direct polycondensation and its application as drug carrier

The hydrophobic modification of sodium alginate was realized by direct grafting with glycolic acid. The products, polyglycolic acid grafting from sodium alginate (Alg-g-PGA), self-assembled into nanoparticles of 200–250 nm in diameter through the interaction of hydrophobic PGA segments in the aqueous solution. Alg-g-PGA nanoparticles were cross-linked into hydrogel microspheres by calcium chloride, which was used as drug delivery vehicles for controlled release. The results of drug (ibuprofen) release model exhibited high drug loading rate and prolonged drug release speed of the Alg-g-PGA gel microspheres. The one-step method of synthesizing hydrophobically modified sodium alginate processes simple operation, mild condition, and low-cost raw material, resulting in its wide application of biological medicine in the future.

Model of the formation of dibenzoylmethanatoboron difluoride exciplexes with aromatic hydrocarbons on silica surface

Dibenzoylmethanatoboron difluoride (DBMBF2) is a fluorophore capable of forming exciplexes with benzene and its derivatives in solutions [1] or in the adsorbed state on the silica gel surface by reacting with vapor of these substances [2, 3], a property that may be used for the fabrication of highly selective and responsive sensor devices. In this study, the dependence of the fluorescence spectra of silica-supported DBMBF2 samples on the vapor concentration of the aromatic compounds benzene, toluene, and p-xylene has been examined. A model describing the observed spectral changes has been proposed. The data on the concentration dependence of the fluorescence spectra of silica gel microspheres bearing adsorbed DBMBF2 are in good agreement with the proposed model.

Invited Commentary

Invited Commentary

Injectable Microsphere Gel Progressively Improves Global Ventricular Function, Regional Contractile Strain, and Mitral Regurgitation After Myocardial Infarction

There is continued need for therapies which reverse or abate the remodeling process after myocardial infarction (MI). In this study, we evaluate the longitudinal effects of calcium hydroxyapatite microsphere gel on regional strain, global ventricular function, and mitral regurgitation (MR) in a porcine MI model. Twenty-five Yorkshire swine were enrolled. Five were dedicated weight-matched controls. Twenty underwent posterolateral infarction by direct ligation of the circumflex artery and its branches. Infarcted animals were randomly divided into the following 4 groups: 1-week treatment; 1-week control; 4-week treatment; and 4-week control. After infarction, animals received either twenty 150 μL calcium hydroxyapatite gel or saline injections within the infarct. At their respective time points, echocardiograms, cardiac magnetic resonance imaging, and tissue were collected for evaluation of MR, regional and global left ventricular function, wall thickness, and collagen content. Global and regional left ventricular functions were depressed in all infarcted subjects at 1 week compared with healthy controls. By 4-weeks post-infarction, global function had significantly improved in the calcium hydroxyapatite group compared with infarcted controls (ejection fraction 0.485 ± 0.019 vs 0.38 ± 0.017, p < 0.01). Similarly, regional borderzone radial contractile strain (16.3% ± 1.5% vs 11.2% ± 1.5%, p = 0.04), MR grade (0.4 ± 0.2 vs 1.2 ± 0.2, p = 0.04), and infarct thickness (7.8 ± 0.5 mm vs 4.5 ± 0.2 mm, p < 0.01) were improved at this time point in the treatment group compared with infarct controls. Calcium hydroxyapatite injection after MI progressively improves global left ventricular function, borderzone function, and mitral regurgitation. Using novel biomaterials to augment infarct material properties is a viable alternative in the current management of heart failure.

Thermogravimetric investigation of sol–gel microspheres doped with aqueous glycerol

Abstract Background Silica-based microspheres encapsulating aqueous glycerol are promising curing agents affording the formation of better one-component polyurethane foams, namely thermoset polymers cured by atmospheric moisture that are widely and increasingly utilized in the construction industry. The use of renewable, non toxic glycerol from biodiesel and oleochemicals industry to cure PU foams in place of traditionally employed oil-derived mono and diethylene glycols is both technically and environmentally beneficial. The higher amount of hydroxyl groups in glycerol compared to both mono- and diethylene glycol results in considerably lower percentage of free monomeric methylene diphenyl diisocyanate (MDI) and higher crosslinking density of the cured foam. Results We investigate by thermogravimetric analysis the nature and amount of the microencapsulated species in sol–gel silica and organosilica microspheres encapsulating aqueous glycerol. Along with a percentage of glycerol in weight up to 35%, the microspheres contain about 5 wt% water and 4 wt% entrapped surfactant. Conclusions The investigation shows the efficacy of the surfactant-assisted sol–gel microencapsulation aqueous glycerol in silica as well as in methyl-silica particles at least until 10% degree of methylation. The results are relevant to the practical development of functional materials that can be used to cure better and greener polyurethane foams largely employed as coatings, adhesives and sealants in many industrial sectors.

Encapsulation of Congo Red in carboxymethyl guar gum–alginate gel microspheres

Congo Red (CR) is a hydrophobic dye commonly used for diagnosis and potentially useful as therapeutic agent of beta amyloid plaques in neurodegenerative diseases. CR, as drug model, was encapsulated on Alginate–Carboxy Methyl Guar Gum (Alg–CMGG) blend microspheres. Guar gum 18% carboxymethylated (CMGG) derivative was synthesized in order to improve aqueous solubility, polymer blending and help reduce surface tension. The derivative was confirmed by FTIR spectroscopy, and elemental analysis. Surface tension of the new CMGG is reduced in about 50% compared with the native polymer. Lowering of Guar Gum (GG) aqueous solutions viscosity from 30,000cps to 350–400cps in case of CMGG is indicating pseudoplastic fluid behavior modifications. Vibrational spectroscopy analysis confirmed interactions among CR molecules in alginate–CMGG matrices ascribed largely to the aromatic motif of the dye and the biopolymer a polar regions. CR was encapsulated on 68/32% alginate/CMGG blend microspheres as the best formulation tested. The release of CR from the microspheres was not detected at pH=1.2 in 25min, but 62% of CR was found in the supernatant when the pH was raised to 7.4 at 37°C after 8h incubation.

Investigation of volatile aliphatic and aromatic amine detection using a fluorescent pH indicator ethyl eosin in polymer matrices

Changes in the fluorescence spectra (F) of ethyl eosin (EE) embedded into polymer matrices of different compositions, gas permeability, and polarity under the action of gaseous aliphatic and aromatic amines (dimethylamine (DMA), trimethylamine (TMA), and pyridine (Pyr)), depending on the pH and the structure of polymer matrix, were investigated. Organic methanesulfonic acid was used to adjust pH in a polymer matrix. Cellulose acetate-propionate (CAP), polyvinyl trimethylsilane (PVTMS), polyethylene oxide (PEO), and polyvinylpyrrolidone (PVP), as well as mesoporous silica gel microspheres, were used as polymer matrices. Absorption and fluorescence maxima of EE in solution and in most polymers are in the region of 505 nm and 550 nm, respectively. The maximum of EE fluorescence intensity increases in all polymer matrices except for PVP in the presence of amines, while the F decreases in the PVP matrix and silica gel microspheres. The fluorescence response to DMA is higher than to TMA and Pyr for all the polymers; the F response is two-phase in the case of Pyr: an increase in F followed by a decrease. Characteristic response times for different matrices change in a sequence: CAP < PVP < PEO < MS < PVTMS. These differences are probably due to the different contributions to the process of the analyte diffusion, its affinity to the polymer, and the internal polarity of the polymer matrix for different polymers.

Effect of pH Value of the Broth on the Gelled Microspheres Containing Zirconium Prepared by Internal Gelation Process

The internal gelation process was used to produce gel microspheres containing Zr. The effect of the broth composition particularly pH value on the stability of the broth and morphology of the dried spheres was investigated. The results indicated that the stability of the broth at room temperature increased with the decrease of the pH of the broth. When the pH of the broth was in the range of 1 to 2 the spheres obtained had good sphericity and uniform size and at pH of 1.35 the spheres were transparent.

Preparation and adsorption of bovine serum albumin-imprinted polyacrylamide hydrogel membrane grafted on non-woven polypropylene

Bovine serum albumin (BSA) imprinted polypropylene (PP) fiber-grafted polyacrylamide (PAM) hydrogel membrane (PP-g-PAM MIP) was prepared using non-woven PP fiber as matrix, BSA as template molecule, and acrylamide (AM) as functional monomer via UV radiation-reduced polymerization in an aqueous phase. SEM, FT-IR, DSC and TG were used to characterize the PP grafted PAM hydrogel. Influence factors on the adsorption capacity of PP-g-PAM MIP were investigated, such as monomer concentration, cross-linker concentration, template molecule amount and pH values in BSA solution. The adsorption and recognition properties of PP-g-PAM MIP were evaluated and the results showed that the PP-g-PAM MIP exhibited an obvious improvement in terms of adsorption capacity for BSA as compared with non-imprinted ones. PP-g-PAM MIPs could recognize the template protein using Lys, Ova, BHb, and Glo as control proteins, and the selectivity factor (β) was above 2.0. The imprinting efficiency of PP-g-PAM MIP tended to be stable after three cycles and maintained 76% of the initial value of the imprinting efficiency even after five repetitions, which was more excellent than that of PAM microsphere. The PP-g-PAM MIP is low cost and easy to be prepared, which would show its potential applications in the fields of extracting and testing required proteins from cells or particulate samples.

A Facile Synthesis of Nanocrystalline Spherical TiO2 Particles and its Photoluminescent Properties

Spherical Titanium dioxide (TiO2) particles were successfully synthesized by sol-gel process in oil-in-water emulsion. Hydrothermal treatment was adopted to induce crystallization of the amorphous gel microspheres. The resulting particles show spherical structure and are suspended without coagulation. Doping and hydrothermal treatment had no obvious effect on the morphology of the TiO2 microspheres. The grain size obtained by XRD analysis is about 6nm. However, doping changed the PL properties of microspheres that the green emission was suppressed by Zn2+ doping.

Enhanced One-Component Spray Polyurethane Foams via Sol–Gel Microspheres Doped with Aqueous Glycerol

The sol–gel microencapsulation of aqueous glycerol in silica-based microspheres affords functional materials that can be used to cure one-component polyurethane foams (OCF) formulations affording better and greener foam formation. These findings are important and may open the route to more sustainable materials, such as foams, coatings, adhesives, and sealants that are widely utilized in many industrial sectors.

Facile Preparation of Core-Shell Nanocomposite Microgels

Microgels with alginate (Alg) gel cores and shells of SiO2 nanoparticles (so-called colloidosomes) were prepared by self-assembly of SiO2 nanoparticles at ALG aqueous solution–hexane interfaces and subsequent in situ gelation caused by Ca2+ ions that were released from calcium-ethylenediamine tetraacetic acid chelate by decreasing the pH value through the slow hydrolysis of D-Gluconic-δ-lactone. The packing density of SiO2 nanoparticles in the shell was about 0.906, indicating that the SiO2 nanoparticles were present monolayer on the surfaces of the colloidosomes. The half release times of insulin microcrystals were 4 h for Alg gel microspheres and 10 h for Alg/SiO2 colloidosomes at pH 7.4, compared to 1.5 h for bare insulin. The half release times of insulin microcrystals were 12 min for Alg gel microspheres and 30 min for Alg/SiO2 colloidosomes at pH 1.2, compared to 30 s for bare insulin. The release rates of insulin from the colloidosomes with core–shell structure were slower than that from bare insulin crystals due to the dual barriers of the hydrogel cores and the close-packed inorganic shells. The release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion.