Calcium Pectinate Gel Beads Research Articles

Encapsulated drug system based on the gels obtained from callus cultures modified pectins

The aims of this research were to obtain modified pectins of callus cultures using various culture conditions, to evaluate the relationship between the chemical characteristics of pectins, the swelling behavior and the release of prednisolone from calcium pectinate gel (CaPG) beads. An increase of the calcium concentration in the culture media correlated significantly with the rhamnogalacturonan I (RG-I) branching of the pectin. The beads from the pectin with a higher RG-I branching had the lower prednisolone release in a gastric fluid. The beads produced from the pectins obtained from callus cultured with a higher calcium concentration showed the lower prednisolone release. The swelling of the CaPG beads from pectin with a lower molecular weight (Mw) or linearity occurred to a lower degree. All beads prepared from modified pectins showed a high stability and a slow liberation of prednisolone in the simulated gastric and intestinal fluids, whereas rapid drug release in a colonic fluid. An applied strategy involving modification of the pectic structure using the abiotic factors allows obtaining the pectic gels with modified functional properties, in particular, with enhanced gastric and small intestinal resistance and a low drug release. These CaPG beads can be applied as the carriers for colon delivery of the drugs.

Adhesive properties of calcium pectinate gels prepared from callus cultures pectins

The aim of this research is to investigate the influence of the surface morphology of the calcium pectinate gel (CaPG) beads as well as the physicochemical characteristics of pectins and the CaPG beads on the adhesive properties of gels against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Bacillus subtilis. The adhesion of the bacteria depends on the type of pectin and the surface morphology of the beads. The faster adhesion on CaPG beads appeared to be related to a lower degree of methyl esterification (DE), a higher molecular weight (Mw) and specific viscosity of the pectin and a higher gel strength. Surface roughness measurements were performed using an atomic force microscope. The beads from pectins with a higher Mw, a higher specific viscosity and a lower DE had a higher surface roughness. The surface roughness was one of the factors promoting adhesion of the bacteria onto the calcium pectinate gels. The surface morphology was observed under a scanning electron microscope (SEM). SEM images illustrated that E. coli and B. subtilis adhered on the beads with a rough surface. CaPG beads obtained from callus culture pectins can be proposed for the preparation of gels with adhesive and antiadhesive properties.

Treated calcium pectinate beads for the covalent immobilization of β-d-galactosidase

The calcium pectinate (CP) gel beads were treated with polyethyleneimine (PEI) and glutaraldehyde (GA). This treatment greatly enhanced the beads’ mechanical strength. Moreover, it enabled the CP beads to covalently immobilize enzymes, such as β-d-galactosidase (β-gal). The central composite design (CCD) was applied to optimize the PEI/GA treatment while employing the observed activity of the immobilized β-gal as a response. The CCD predicted that treating the CP beads with a 3.49% PEI solution of pH 10.55, followed by a 5.66% GA solution in 0.1M phosphate buffer pH 7.02 would allow for the immobilization of 6.25U/g gel of the β-gal. The verification experiment run at these optimum conditions offered 6.285±0.22U/g gel immobilized β-gal which was in close agreement with the predicted value. The reusability study revealed that the β-gal immobilized onto the treated CP beads retained 79.34% of its initial activity after being used for fourteen times.

Calcium pectinate gel beads obtained from callus cultures pectins as promising systems for colon-targeted drug delivery

Low methyl-esterified pectins obtained from the cell walls of the campion (SV, SV>300), tansy (TV, TV>300) and duckweed (LM, LM>300) callus cultures and apple pectin (AP, Classic AU 701) were used as the carriers for colon delivery of prednisolone. The pectins with molecular weight more than 300kDa (SV>300, TV>300, LM>300) formed gels which exhibited the higher gel strength. The higher gel strength of these gels appeared to be related to the higher Mw and the lower degree of methylesterification (DE) of these pectins. Release aspects of prednisolone in the simulated gastric (pH 1.25), intestinal (pH 7.0) and colonic (pH 7.0+pectinase) media were investigated. The LM-5%, AP-3% and AP-5% beads destroyed in simulated intestinal medium probably due to the higher DE of the LM and AP pectins. The SV>300-3% and TV>300-3% prednisolone loaded bead systems showed a high stability at pH 1.25 and pH 7.0. Prednisolone release occurred in a larger extent in colonic medium due to the enzymatic erosion of the beads. The SV>300-3% and TV>300-3% particles showed a more controlled release that appeared to be related to the lower DE, rhamnogalacturonan content, rhamnogalacturonan I branching and the higher linearity and Mw of the TV>300 and SV>300 pectins, as well as to the higher gel strength. This in vitro study suggests that calcium pectinate gel beads obtained from callus cultures pectins can be proposed as potential systems for colon-targeted drug delivery.

Gastroretentive Drug Delivery System of Famotidine: Formulation and In Vitro Evaluation of Oil Entrapped Calcium Pectinate Gel Beads

In the present research envisaged was to prepare gastroretentive beads to increase the retention time in stomach and to modulate the release pattern from the gel beads. The aim of the research work to study the compatibility between drug and other polymers by differential scanning calorimetric analysis, preparation of cod liver oil entrapped calcium pectinate gel beads of famotidine by emulsion gelation method and its evaluation. The gel beads were prepared by employing low methoxy pectin with degree of esterification less than 50% alone and with hydrophilic co polymers carbopol 934P, hydroxypropyl methylcellulose K15M and polycarbophil to study the effect of these co polymers on drug release. The prepared gel beads were subjected for various evaluations like topographical study of whole and dissected bead, percent drug entrapment efficiency, buoyancy and in vitro drug release study in conventional and modified flow through dissolution methods. The prepared beads showed ideal buoyancy, low methoxy pectin gel matrix could not sustain the drug release and presence of co polymers demonstrated sustained release. These observations suggested that cod liver oil entrapped calcium pectinate beads were promising as a carrier for intragastric floating drug delivery of famotidine.

Swelling and morphology of calcium pectinate gel beads obtained from Silene vulgaris callus modified pectins

The aim of this research is to investigate the swelling properties and morphology of the calcium pectinate gel (CaPG) beads made from pectins of campion callus cultured using various medium nutrients (carbon sources, concentration of sucrose, calcium and 2,4-dichlorophenoxyacetic acid (2,4-D)). Gelled spheres were prepared by ionotropic gelation. The mean diameter, total surface area and volume of the dried beads varied depending on the plant cell culture conditions. The swelling of dried CaPG beads in solutions with pH 2 and pH 4 was demonstrated to occur more slowly (within 4 or 24h) with increasing sucrose and calcium concentrations or in the absence of auxin. All beads swelled less when placed in acidic media (pH 2 and pH 4) and swelled most extensively in NaCl (pH 6). The surface morphology of the CaPG beads was demonstrated to depend on the presence of sugars, calcium and auxin in the plant cell culture medium used. The slow swelling of dried CaPG beads was apparently related to their grooved surfaces. An applied strategy involving changing the composition and concentration of media components altered the swelling behavior of the CaPG beads and enhanced the acid and water resistance of the resultant pectinate hydrogels in physiological environments. In particular, the swelling of Ca 4.5, 2,4-D0, Suc30 and Suc100 CaPG beads occurred more slowly.

Study of saponins and phenolic compounds and their antioxidant activities in some Silene species

The aim of this research is to investigate the swelling properties and morphology of the calcium pectinate gel (CaPG) beads made from pectins of campion callus cultured using various medium nutrients (carbon sources, concentration of sucrose, calcium and 2,4-dichlorophenoxyacetic acid (2,4-D)). Gelled spheres were prepared by ionotropic gelation. The mean diameter, total surface area and volume of the dried beads varied depending on the plant cell culture conditions. The swelling of dried CaPG beads in solutions with pH 2 and pH 4 was demonstrated to occur more slowly (within 4 or 24 h) with increasing sucrose and calcium concentrations or in the absence of auxin. All beads swelled less when placed in acidic media (pH 2 and pH 4) and swelled most extensively in NaCl (pH 6). The surface morphology of the CaPG beads was demonstrated to depend on the presence of sugars, calcium and auxin in the plant cell culture medium used. The slow swelling of dried CaPG beads was apparently related to their grooved surfaces. An applied strategy involving changing the composition and concentration of media components altered the swelling behavior of the CaPG beads and enhanced the acid and water resistance of the resultant pectinate hydrogels in physiological environments. In particular, the swelling of Ca 4.5, 2,4-D0, Suc30 and Suc100 CaPG beads occurred more slowly.

Effect of Drug Loading Method on Drug Content and Drug Release from Calcium Pectinate Gel Beads

Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studies in 0.1 N hydrochloric acid (HCl) and pH 6.8 buffer indicated that the drug loading method affected drug release and release parameter, time for 50% of drug release (T(50)). The mixing method provided a faster drug release and lower T(50) than the absorption method and swelling method, respectively. This is probably due to higher drug content in CaPG beads. The increased concentration of drug in soaking solution and soaking time resulted in higher drug content and thus faster drug release (lower in T(50) values). When using 0.1 N HCl as solvent for soaking instead of water, the drug release was slower owing to the increase in molecular tortuosity of CaPG beads. The drug release was also affected by pH of the release medium in which drug release in 0.1 N HCl was faster than in pH 6.8 buffer.

Characteristics and antioxidant activity of catechin-loaded calcium pectinate gel beads prepared by internal gelation

Catechin-loaded calcium pectinate gel beads prepared by internal gelation were characterized for their catechin entrapment efficiency and release behavior. The entrapment efficiency was higher when the beads were prepared with a lower catechin-to-pectin ratio, shorter gelling time, higher pectin concentration, and lower acetic acid concentration. The entrapment efficiency was much higher under all tested conditions, when the beads were prepared by internal gelation instead of external gelation. The catechin release was slower for the beads prepared with lower catechin-to-pectin ratio, longer gelling time, and higher concentrations of pectin and acetic acid in both simulated gastric and intestinal fluids. Antioxidant power of catechin was effectively maintained in alkaline simulated intestinal fluid when catechin was entrapped within the beads, compared to cases where it was not entrapped, indicating that the beads can protect catechin molecules from the alkaline environment and release them in a sustained fashion.

Optimization of calcium pectinate gel beads for sustained-release of catechin using response surface methodology

Response surface methodology was used to optimize bead preparation conditions, including CaCl 2 concentration ( X 1), hydroxypropylmethylcellulose concentration ( X 2), and bead-hardening time ( X 3), for the sustained-release of catechin from the calcium pectinate gel beads reinforced with liposomes and hydroxypropylmethylcellulose into simulated gastric fluid (SGF) and intestinal fluid (SIF). The optimized values of X 1, X 2, and X 3 were found to be 5.82%, 0.08%, and 10.29 min, respectively. The beads prepared according to the optimized conditions released only about half of the entrapped catechin into SGF while most of the entrapped catechin was released into SIF after 24 h incubation.

Effect of Acidic Medium on Swelling and Release Behaviors of Chitosan-Reinforced Calcium Pectinate Gel Beads

Chitosan-reinforced calcium pectinate (ChCP) gel beads were prepared by ionotropic gelation method. Theswelling of ChCP gel beads and release behavior of indomethacin from the beads were investigated and comparedwith conventional calcium pectinate (CP) gel beads. The factors, such as molecular weight of chitosan,concentration of chitosan, and release medium, which can have a significant effect on the swelling and releasebehaviors from the beads, were discussed in this study. The mechanical test showed that the ChCP beads haveslightly higher strength than that of CP beads. The swelling index of the ChCP beads in acidic medium was muchlower than that in neutral medium. The release of indomethacin from ChCP beads under conditions mimickingintestinal transit were evaluated in pH 7.4 Tris buffer. The acid pretreatment caused a faster drug release fromChCP beads. The less swelling in acidic medium and faster drug release of acid-pretreated ChCP beads may bedue to the dissolution of chitosan from the beads in acidic medium, as no fluorescence signal was seen at the shellof the beads. The results suggested that the acid, which essentially found in stomach, influenced the swelling andrelease behaviors of ChCP beads. Key Words: Chitosan; Pectin; Calcium pectinate; Beads; Drug release; Acid pretreatment

Preparation and characterization of calcium pectinate gel beads entrapping catechin-loaded liposomes

Calcium pectinate gel (CPG) beads entrapping catechin-loaded liposomes were prepared with or without hydroxypropylmethylcellulose (HPMC) (denoted as CPG-LH and CPG-L beads, respectively) and characterized in comparison with the CPG beads prepared without liposome and HPMC (denoted as CPG-C beads). For all types of beads, the catechin entrapment efficiency decreased by about 40–50% as the concentration of CaCl 2 in gelling media increased from 2 to 6%. At a constant CaCl 2 level, the entrapment efficiency was higher in the order of CPG-LH, CPG-L, and CPG-C beads. The in vitro release test showed that in simulated intestinal fluid the rate of catechin release was higher in the order of CPG-C, CPG-L, and CPG-LH beads, indicating that the catechin release was slowed by liposome and further retarded when HPMC was used simultaneously, whereas not in simulated gastric fluid. The addition of cholesterol in liposome could not retard but accelerated the catechin release. The results suggest that the CPG beads reinforced with liposome and HPMC could be employed for a sustained oral delivery of catechins, although further improvements are necessary.

Potential of calcium pectinate beads for target specific drug release to colon

A pectin-based colon specific delivery system bearing 5-fluorouracil (5-FU) was developed for effective delivery of drug to the colon. Calcium pectinate gel (CPG) beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S-100. The CPG beads formed were spherical with smooth surfaces. CPG beads size was found to be in the range of 1.32 ± 0.12–1.88 ± 0.08 mm. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Release in PBS (pH 7.4) and simulated gastric fluid showed almost similar pattern and rate, whereas a significant increase in percent cumulative drug release (58.3 ± 1.36%) was observed in medium containing rat caecal content, i.e. the amount of the drug released from the formulation was found to be 49.2 ± 2.29 and 58.3 ± 1.36% of drug with 2 and 4% w/v caecal matter after 24 h whereas in control study 33.2 ± 1.19% of drug was released. Moreover, to induce the enzymes that specifically act on pectin, the rats were treated with 1 ml of 1% w/v dispersion of pectin for 2 and 4 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of caecal matter. A marked improvement in the drug release was observed in presence of caecal matter obtained after induction when compared to those without induction. The percentage of drug released after 24 h release was observed to be 69.3 ± 2.81 and 86.7 ± 3.15%, respectively, with 2 and 4% w/v rat caecal matter obtained after 2 days of enzyme induction, and 82.4 ± 3.15 and 98.7 ± 4.26%, respectively, after 4 days of enzyme induction. In vivo data showed that Eudragit S-100 coated calcium pectinate beads delivered most of its drug load (93.2 ± 3.67%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally-ssadministered 5-FU loaded Eudragit S-100 coated calcium pectinate beads can be used effectively for the specific delivery of drug to the colon.

Use of pectin as a carrier for intragastric floating drug delivery: Carbonate salt contained beads

Pectin has been investigated as a carrier for an intragastric floating drug delivery by a means of calcium pectinate gel (CaPG) beads. The CaPG beads containing carbonate salt, as a gas-forming agent, were prepared by dispersing carbonate salt in pectin solution and then extruding into either neutral or acidified solution of calcium chloride. The effect of selected factors, such as type of carbonates, percentage of carbonates, degree of methylesterification (DE) of pectin, type of gelation medium, drug loading and drying method, on morphology, floating and release properties was investigated. Incorporation of sodium bicarbonate into pectin solution resulted in porous structured beads. Acidity of gelation medium increased the pores in the structure of beads containing calcium carbonate. This is due to carbon dioxide generated from reaction of carbonate salts with acid. Drug release from CaPG beads is clearly dependent upon the formulation and processing variables studied. It is obvious that the highly porous of the freeze-dried beads showed a good floating ability with fast drug release. The drug release could be prolonged by using pectin with lower DE, 10% calcium carbonate, acidified gelation medium, and high drug loading. However, their floating ability seemed to be decreased. It is suggested that the optimization of formulation and processing variables is further needed to obtain a good floating ability and a prolonged drug release.

Microencapsulation of Nanoparticulate Complexes of DNA with Cationic Lipids and Polymers in Pectin Beads for Targeted Gene Delivery

Nanoparticulate complexes of plasmid DNA (pDNA) with cationic liposomes/polymer, of approx 200 nm diameter, were encapsulated with a high degree of efficiency within calcium pectinate gel beads. Electron microscopy showed the DNA nanocomplexes to be evenly distributed throughout the gel matrix. Controlled release of pDNA-lipid nanocomplexes was achieved by the action of pectinase enzymes, whereas release of naked and polymer-complexed DNA was found to be more greatly influenced by the swelling behavior of the polysaccharide matrices in buffer alone. Physical degradation of pDNA within pectin beads was found to be accelerated during bead drying, most probably as a result of shear forces generated within the gel matrices by the evaporation of water. Plasmid complexation with cationic liposomes provided a greater degree of protection for the DNA during bead drying than complexation with cationic polymer, and was shown to successfully transfect cultured cells after release from the beads, via the action of pectinase. Observations concerning the physical stability of nanocomplexed pDNA, and its encapsulation within and release from pectin gel beads, are discussed with reference to the electrostatic interactions existing between the various components.

Morphology and buoyancy of oil-entrapped calcium pectinate gel beads

A new emulsion-gelation method to prepare oil-entrapped calcium pectinate gel (CaPG) beads capable of floating in the gastric condition was designed and tested. The gel beads containing edible oil were prepared by either being gently mixed or homogenized an oil phase and a water phase containing pectin, and then extruded into calcium chloride solution with gentle agitation at room temperature. The gel beads formed were then separated, washed with distilled water, and dried at 37 degrees C for 12 hours. A model of the emulsion-gelation process to illustrate the formation of oil-entrapped CaPG beads was proposed. The effect of selected factors, such as type of oil, percentage of oil, and type of pectin on morphology and floating properties was investigated. The oil-entrapped calcium pectinate gel beads floated if a sufficient amount of oil was used. Scanning electron photomicrographs demonstrated very small pores, ranging between 5 and 40 microm, dispersed all over the beads. The type and percentage of oil play an important role in controlling the floating of oil-entrapped CaPG beads. The results suggested that oil-entrapped CaPG beads were promising as a carrier for intragastric floating drug delivery.

Effect of calcium concentration, hardening agent and drying condition on release characteristics of oral proteins from calcium pectinate gel beads

Pectin has been investigated for its ability to produce solid calcium pectinate gel (CPG) beads containing bovine serum albumin (BSA). Several factors can influence the properties and release characteristics of the CPG beads. In this study, the effect of calcium concentration, hardening agent and drying condition on the encapsulation and release characteristics of BSA from the matrix gel beads made of calcium pectinate were studied. BSA release studies under conditions mimicking mouth to colon transit have shown that calcium pectinate protects the drug from being released completely in the physiological environment of the upper gastrointestinal tract, and is susceptible to the enzymatic action with consequent drug release. In addition, the release of BSA from CPG beads was strongly affected by calcium concentration and drying condition. However, the release was not particularly affected by the presence of hardening agent at the concentration of 1% or lower. Since the release of BSA as a model protein drug could be controlled by the regulation of the preparation conditions of CPG beads, the CPG beads may be used for a potential oral controlled release system for protein drugs.

Calcium pectinate gel beads for controlled release drug delivery: II. Effect of form ulation and processing variables on drug release

The effect of four formulation and processing variables, calcium concentration, drying condition, concentration of hardening agent and hardening time on the bead properties and the release characteristics of a model drug from calcium pectinate gel (CPG) beads were studied. A poorly soluble compound, indomethacin, was used as the model drug. The investigated variables affected the bead size, the entrapment efficiency and the release of indomethacin from CPG beads. Drug release was found to be a function of the formulation and processing variables. The slower drug release was achieved from the formulations with higher calcium concentration, higher concentration of hardening agent and longer hardening time. The drying condition, however, did not influence the drug release. The mechanism of indomethacin release from CPG beads followed the diffusion controlled model for an inert porous matrix. All drug release data fitted well to the Higuchi square root time expression.

Investigation of pectin as a carrier for oral delivery of proteins using calcium pectinate gel beads

A novel oral delivery of protein to the colon based on the polysaccharide pectin has been investigated using bovine serum albumin (BSA) as a model protein. Calcium pectinate gel (CPG) beads were prepared by extruding BSA-loaded pectin solution into agitated calcium chloride solution. Subsequent drying produced matrix beads in which BSA were embedded. In vitro experiments were conducted on the release of BSA from the CPG beads under conditions pertaining to those in vivo. Monitoring of release gives a sensitive indication of the behavior of pectin under the different conditions. The type of pectin and the presence of enzymes in the medium influence release characteristics. By changing the type of pectin it is possible to protect BSA during conditions of mouth to colon transit and susceptibility to enzymatic attack. Additionally, the release of BSA from CPG beads was strongly affected by cross-linking time but not particularly affected by the amount of protein added. The investigated factors also influenced bead sizes and entrapment efficiency. The results suggest that calcium pectinate gel beads are promising as a carrier for oral delivery of protein by means of colonic delivery.

Calcium pectinate gel beads for controlled release drug delivery:: I. Preparation and in vitro release studies

Calcium pectinate gel (CPG) beads of indomethacin, a poorly soluble drug, were prepared by dispersing indomethacin in a solution of pectin and then dropping the dispersion into calcium chloride solution. The droplets instantaneously formed gelled spheres by ionotropic gelation. The effect of several factors such as pectin type, the presence of a hardening agent and the drug loading were investigated on the percentage of drug entrapped, size distribution and drug release from the CPG beads. The release characteristics were studied using the rotating basket dissolution method. Strong spherical beads with narrow size distributions, high yields and good entrapment efficiencies could be prepared. All factors investigated have significantly affected the release of indomethacin from CPG beads. The mechanism of drug release from CPG beads followed the diffusion controlled model for an inert porous matrix. Therefore, calcium pectinate gel could be a useful carrier for controlled release drug delivery of poorly soluble drugs.