Polyelectrolyte Complex Beads Research Articles

Development of Polyelectrolyte Complex Beads Containing Vancomycin Hydrochloride for Colon-targeted Drug Delivery

Development of Polyelectrolyte Complex Beads Containing Vancomycin Hydrochloride for Colon-targeted Drug Delivery

Methacrylated Gellan Gum/Poly-l-lysine Polyelectrolyte Complex Beads for Cell-Based Therapies.

Cell encapsulation strategies using hydrogel beads have been considered as an alternative to immunosuppression in cell-based therapies. They rely on layer-by-layer (LbL) deposition of polymers to tune beads' permeability, creating a physical barrier to the host immune system. However, the LbL approach can also create diffusion barriers, hampering the flow of essential nutrients and therapeutic cell products. In this work, the polyelectrolyte complex (PEC) methodology was used to circumvent the drawbacks of the LbL strategy by inducing hydrogel bead formation through the interaction of anionic methacrylated gellan gum (GG-MA) with cationic poly-l-lysine (PLL). The interfacial complexation between both polymers resulted in beads with a cell-friendly GG-MA hydrogel core surrounded by a PEC semipermeable membrane. The beads showed great in vitro stability over time, a semi-permeable behavior, and supported human adipose-derived stem cell encapsulation. Additionally, and regarding immune recognition, the in vitro and in vivo studies pointed out that the hydrogel beads behave as an immunocompatible system. Overall, the engineered beads showed great potential for hydrogel-mediated cell therapies, when immunoprotection is required, as when treating different metabolic disorders.

Polyelectrolyte complex beads of carboxymethylcellulose and chitosan: The controlled formation and improved properties

Spherical beads made of naturally derived polymers can be widely used as a promising matrix in many bio-related and safety required fields. Herein, the optimal parameters for fabrication of a core-shell bead composed of carboxymethylcellulose (CMC) and chitosan (CHI) are established based on systematic investigations on working distance, solution pH and polymer concentrations. Spherical beads will be obtained when the working distance is set as 15 cm. The beads prepared at pH 4.5 are the strongest and can resist to a force of up to 0.071 N. It will be shown that the critical concentration of polymer solutions plays important roles in determining the shape and size of beads. The observation of two new peaks at 1723 cm−1 and 1592 cm−1 in the FTIR of the prepared beads demonstrate the electrostatic interactions between CMC and CHI. With a post gentle heating (35°C), the stability of beads is significantly improved and the swelling degree in water increases to 220%.

Cellulose sulfate/EMIMAc solution: rheological properties and shaping into polyelectrolyte complexes for protein adsorption

Cellulose sulfates (CS) with low degree of substitution (DS) and high degree of polymerization (DP) were prepared via a controlled sulfation modification. The obtained CS with DS 0.42 and DP 293 showed an enhanced solubility of 14.7 g/100 g in the ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIMAc) compared to unmodified cellulose. The rheological study revealed that the CS/EMIMAc solution behaved as polymers in a θ solvent with the unique three-region flow curves under shear stress. It also showed a property of typical polyelectrolyte solution with the overlap concentration (c*) of 0.2 wt% and the entanglement concentration (ce) of 3.0 wt%, respectively. The CS/EMIMAc solution with a concentration of 5 wt% was selected to develop polyelectrolyte complex (PEC) with chitosan using extrusion-spherization and emulsification-solvent evaporation. The produced PEC beads and magnetic microspheres had an average size of 1.0 mm and 22.1 µm, respectively. The PEC microspheres showed greater absorption capability for bovine serum albumin than the beads with the maximum adsorption value of 780 mg/g.

Immobilized Cell Physiology Imaging and Stabilization of Enzyme Cascade Reaction Using Recombinant Cells Escherichia coli Entrapped in Polyelectrolyte Complex Beads by Jet Break-Up Encapsulator

A novel, high performance, and scalable immobilization protocol using a laminar jet break-up technique was developed for the production of polyelectrolyte complex beads with entrapped viable Escherichia coli cells expressing an enzyme cascade of alcohol dehydrogenase, enoate reductase, and cyclohexanone monooxygenase. A significant improvement of operational stability was achieved by cell immobilization, which was manifested as an almost two-fold higher summative product yield of 63% after five cascade reaction cycles as compared to the yield using free cells of 36% after the maximum achievable number of three cycles. Correspondingly, increased metabolic activity was observed by multimodal optical imaging in entrapped cells, which was in contrast to a complete suppression of cell metabolism in free cells after five reaction cycles. Additionally, a high density of cells entrapped in beads had a negligible effect on bead permeability for low molecular weight substrates and products of cascade reaction.

Superhydrophobic Substrates for Ultrahigh Encapsulation of Hydrophilic Drug into Controlled-Release Polyelectrolyte Complex Beads: Statistical Optimization and In Vivo Evaluation.

In this work, ultrahigh drug-loaded chitosan (Ch)/K-carrageenan (Kc) polyelectrolyte complex (PEC) beads were formed in situ by cross-linking in a glutaraldehyde-saturated atmosphere and were prepared on superhydrophobic substrates fabricated by spraying glass surfaces with ready-made spray for domestic use (NeverWet®). Verapamil hydrochloride (VP), a highly hydrophilic drug with a short biological half-life, was incorporated into a series of Ch-based and/or Ch/Kc-PEC-based beads to control its release profile in vivo. The formulation of VP-loaded beads was optimized using stepwise statistical designs based on a prespecified criterion. Several characteristics of the prepared beads, such as entrapment efficiency (EE%), in vitro drug release, swelling ratio, size and surface microstructure as well as molecular interactions between the drug and formulation ingredients, were investigated. In vivo pharmacokinetic (PK) studies were carried out using the rabbit model to study the ability of the optimized VP-loaded beads to control the absorption rate of VP. Results revealed that the prepared superhydrophobic substrates were able to fabricate VP-loaded beads with extremely high EE exceeding 90% w/w compared to only 27.80% when using conventional ionotropic gelation technique. PK results showed that the rate of VP absorption was well controlled following oral administration of the optimized beads to six rabbits compared to a marketed VP immediate release (IR) tablet, as evidenced by a 2.2-fold increase in mean residence time (MRT) and 5.24-fold extension in half value duration (HVD) over the marketed product without any observed reduction in the relative oral bioavailability.

Fabrication of chitosan-alginate polyelectrolyte complexed hydrogel for controlled release of cilnidipine: a statistical design approach

In the present investigation, fabrication and statistical optimization of chitosan-alginate polyelectrolyte complex (PEC) beads were performed for controlled delivery of Cilnidipine (CIL). PEC beads containing CIL were prepared by ionic cross-linking with calcium chloride. A statistical optimization was performed by employing a 32 full factorial design. Graphical optimization using overlay plot provides optimum combination of both the factors with the desired ranges of response. The optimum formulation of CIL (CB-O) was developed employing sodium alginate (2·2%w/v) and chitosan (1·2% w/v). CB-O formulation showed particle size (mm) =1·62 ± 0·42; DEE (%) = 90·21 ± 1·66; and drug release (%) = 89·58 ± 1·93; furthermore, solid state characterization by DSC, SEM, and XRD analysis reveals uniform dispersion of drug in polymer matrix. Controlled release CIL beads may find future perspectives in enhancing patient compliance by the abrupt reduction in side effects and dose frequency owing to effective therapeutic efficacy as indicated by the in-vitro study.

A Review on Stability of Aloe Vera Gel

Aloe is the dried juice of the leaves of Aloe barbadensis Miller, known as Curacao aloes; or of Aloe perryi Baker, known as Socotrine aloes; or of Aloe ferox Miller and hybrids of this species with Aloe Africana Miller and Aloe spicata Baker, known as Cape aloes, belonging to family Liliaceae.1. The aim of the present review article is to study different methods to overcome the stability problem of aloe gel. This review article deals with methods like selection and optimization of gelling agent, use of high hydrostatic pressure for processing and formulation of polyelectrolyte complex beads to enhance stability of aloe gel. Carboxy methylcellulose sodium, Carbomer 934, HPMC and different concentration of viscosity enhancer can be used to increase the stability of aloe gel. High hydrostatic pressure (HHP) is an innovative emerging technology to increase the stability of aloe vera gel. High Hydrostatic Pressure involves the application of pressure on the product within a range of 50 to 1000 MPa. It has been reported that pressure up to 350 MPa can be applied to plant systems without any major effect on texture and structure. Another method to overcome the stability problem of aloe gel is formulation of polyelectrolyte-complex beads using chitosan-sodium alginate and suspending them into calamine lotion. The gels obtained by using either of above methods were evaluated for pH, colour, viscosity and stability.

Polyelectrolyte Complex Beads by Novel Two-Step Process for Improved Performance of Viable Whole-Cell Baeyer-Villiger Monoxygenase by Immobilization

A novel immobilization matrix for the entrapment of viable whole-cell Baeyer–Villiger monooxygenase was developed. Viable recombinant Escherichia coli cells overexpressing cyclohexanone monooxygenase were entrapped in polyelectrolyte complex beads prepared by a two-step reaction of oppositely-charged polymers including highly defined cellulose sulphate. Immobilized cells exhibited higher operational stability than free cells during 10 repeated cycles of Baeyer–Villiger biooxidations of rac-bicyclo[3.2.0]hept-2-en-6-one to the corresponding lactones (1R,5S)-3-oxabicyclo-[3.3.0]oct-6-en-3-one and (1S,5R)-2-oxabicyclo-[3.3.0]oct-6-en-3-one. The morphology of polyelectrolyte complex beads was characterised by environmental scanning electron microscopy; the spatial distribution of polymers in the beads and cell viability were examined using confocal laser scanning microscopy, and the texture was characterised by the mechanical resistance measurements.

The Size and Morphological Study of Spherical Polyelectrolyte Complex Beads Using Environmental Scanning Electron Microscopy

The Size and Morphological Study of Spherical Polyelectrolyte Complex Beads Using Environmental Scanning Electron Microscopy

Preparation and cytotoxicity of N,N,N-trimethyl chitosan/alginate beads containing gold nanoparticles

Polyelectrolyte complex beads based on N,N,N-trimethyl chitosan (TMC) and sodium alginate (ALG) were obtained. This biomaterial was characterised by FTIR, TGA/DTG, DSC and SEM analysis. The good properties of polyelectrolyte complex hydrogel beads were associated, for the first time, with gold nanoparticles (AuNPs). Through a straightforward methodology, AuNPs were encapsulated into the beads. The in vitro cytotoxicity assays on the Caco-2 colon cancer cells and healthy VERO cells showed that the beads presented good biocompatibility on both cell lines, whereas the beads loaded with gold nanoparticles (beads/AuNPs) was slightly cytotoxic on the Caco-2 and VERO cells.

Simple preparation of polyelectrolyte complex beads for the long-term release of small molecules.

We report a simple method for preparing solid polyelectrolyte complex (PEC) beads, which provide effective barriers to diffusion and can be used for the multiple-day release of small molecules. Single-phase poly(allylamine) (PAH) and poly(styrenesulfonate) (PSS) mixtures were prepared at pH 11.6 (significantly above the effective pKa of PAH), where the PAH amine groups were deprotonated and therefore neutral. These mixtures were added dropwise into acid baths, whereupon the rapid acid diffusion into the polyelectrolyte droplets led to instant ionization of PAH amine groups and, thus, the formation of PEC beads (i.e., via phase inversion). In stark contrast to the PEC particles prepared through phase inversion in previous studies, which had (solvent-filled) capsule-like morphologies, these beads had solid internal structures. The solute permeabilities of these PEC matrices could be extensively tuned by air drying the beads, which led to the apparently-irreversible closure of pores. Thus, by tuning the drying conditions and polymer compositions used during bead preparation, a model small molecule (Fast Green FCF dye) was released over times ranging between 2 and 18 days.

Effect of Formulation Variables on Dissolution of Water-Soluble Drug from Polyelectrolyte Complex Beads

This study was planned to develop chitosan-based polyelectrolyte complex (PEC) beads for the prolonged release of the water-soluble drug, verapamil HCl (VPL). The PEC beads were prepared by an ionic gelation method using positively charged chitosan (CH) and negatively charged sodium alginate (ALG), carboxymethylcellulose sodium (CMC), and k-carrageenan (CAR). The surface morphology was investigated by scanning electron microscopy (SEM), and PEC formation was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. Gel beads were evaluated for particle size, drug entrapment efficiency, swelling behavior, and in vitro release. The SEM study confirmed that spherical or disc-shaped beads were formed by changing the counterion and pH of the coagulation medium. DSC and FTIR spectroscopy confirmed the PEC formation. The mean particle size was 556–896 μm, and drug entrapment efficiency was more than 80%. The beads showed pH-sensitive swelling with less swelling in hydrochloric acid buffer (pH 1.2) and more swelling in phosphate buffer (pH 7.4). The in vitro release of VPL was very slow in HCl buffer as compared with phosphate buffer. The concentration of chitosan, anionic polymers, and the pH of the coagulation medium significantly affected the size, entrapment efficacy, swelling, and release pattern of PEC beads. INTRODUCTION Polycationic chitosan (CH) is prepared through deacetylation of chitin. Chitosan is an important biopolymer having wide pharmaceutical application (1). Chitosan polyelectrolyte complexes (PEC) are ideal substitutes for covalently cross-linked hydrogels. The formation of a PEC requires only polycationic and polyanionic polymers without catalysts or initiators, and the reaction is generally performed in aqueous solution, which is the main advantage over covalently cross-linked polymeric networks. Therefore PEC offers biocompatibility and avoids the purification step to minimize the toxicity associated with the unreacted covalent cross-linking agents before administration (2–6). The electrostatic attraction between the amino groups of CH and the carboxylic–sulfate groups of anionic polymers is the main interaction leading to the formation of the PEC (7). PECs can be cross-linked by the addition of ions to form ionically cross-linked systems, for instance, calcium ions can be added to alginate (8), and pectin (9) and aluminum ions can be added to carboxymethylcellulose (4). Chitosanbased PECs are well-tolerated systems and can be used in various applications such as drug delivery systems (10). Verapamil hydrochloride (VPL) is a freely water-soluble calcium channel blocker used in the treatment of angina pectoris, hypertension, and supraventricular tachyarrhythmias (11, 12). Upon oral administration, 90% of drug is absorbed from the gastrointestinal tract, but it has low bioavailability of 22% with a biological half-life of 4 ± 1.5 h (13). In the present study, polyelectrolyte complex beads were prepared using CH (cationic polymer) along with three anionic polymers (sodium alginate, carboxymethylcellulose sodium, and k-carrageenan) for prolonged release of the water-soluble drug, VPL. The effect of the concentrations of CH and counter ions and the pH of the coagulation medium on the formation and performance of PEC beads was studied. MATERIALS AND METHODS Materials Verapamil HCl was a kind gift sample from Unicure Pvt. Ltd. (India) and Torrent Pharmaceuticals Ltd. (India). Chitosan (minimum 80% deacetylated) was a gift sample from Mahtani Chitosan Pvt. Ltd. (India). Sodium alginate (ALG) was obtained from Snap Natural and Alginate Pvt. Ltd. (India). -Carrageenan (CAR) was obtained from Sigma-Aldrich (USA). Carboxymethylcellulose sodium (CMC), calcium chloride, aluminum chloride, potassium chloride, and glacial acetic acid were obtained from SD Fine Chem Ltd. (India). Methods Preparation of PEC Beads The preparation details of PEC beads are given in Table 1. PEC beads were prepared by an ionic gelation method using varied concentrations (0.5%, 1%, and 1.5% w/w) of CH along with fixed concentrations of ALG, CMC, and CAR in the presence of calcium, aluminum, and potassium as counter ions. The amount of VPL was kept constant (1% w/v). Homogeneous aqueous solutions of CH and calcium chloride/aluminum chloride/potassium chloride were *Corresponding author. e-mail: rvkulkarni75@yahoo.com ssaleempharm@rediffmail.com dx.doi.org/10.14227/DT190412P21

Polyelectrolyte complex beads composed of water‐soluble chitosan/alginate: Characterization and their protein release behavior

AbstractPolyelectrolyte complex (PEC) beads were prepared from water‐soluble chitosan (WSC) and alginate complex solution with different ratios by dropping method, and all procedures used were performed in aqueous medium at neutral environment. The structure and morphology of the beads were characterized by IR spectroscopy and scanning electron microscopy (SEM). IR spectroscopy confirmed the electrostatic interactions between amino groups of WSC and carboxyl groups of alginate. SEM showed internal section of the PEC bead, which had porous structure compared with compact structure of alginate beads. The swelling behavior, encapsulation efficiency, and release behavior of bovine serum albumin (BSA) from the beads at different pHs were investigated. PEC beads demonstrated different responses to pH from alginate beads. The ratio of WSC to alginate influenced the encapsulation and release of BSA. At pH 1.2, small amount (< 15%) of BSA was released from the PEC beads except AC12. However, at pH 7.4, a large amount (> 80%) of BSA was released from AL in the first 3 h due to the rapid disintegration of the beads, whereas BSA release was retarded from complex beads due to the forming of PEC. The results suggested that the WSC/alginate beads could be a suitable polymeric carrier for site‐specific protein drug delivery in the intestine. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4614–4622, 2006

Development of a new technology for the production of microcapsules based in atomization processes

A new microencapsulation technology of polyelectrolyte complex beads which produce very small particles (1–50 μm) with particle size control has been developed. The polymers used were sodium alginate as polyanion and barium chloride as polycation. To do that, an air-blast atomizer that uses compressed air was used. This works by spraying a solution of sodium alginate in a solution of barium chloride, which induces the gelation. The air flow rate, alginate flow rate and viscosity of the alginate solution effects were studied. The behaviour curves of the system were built with the microparticles size data obtained at different operation conditions. These curves will allow knowing the operation conditions for a suitable microparticle size.