Preparation and characterization of coacervate microcapsules for the delivery of antimicrobial oyster peptides

Oyster peptides-loaded alginate/chitosan/starch microcapsules were prepared using external gelation method and internal emulsion gelation method. The solution of oyster peptides complexes was encapsulated into the microcapsules, which endowed the microcapsules with intestine passive targeting properties. The swelling behavior, encapsulation efficiency, and release behavior of oyster peptides from the microcapsules at different pH values were investigated. The microcapsules exhibited sustained release of the peptides in intestinal medium, and the release rate could be regulated by the pH value: in simulated gastric fluid, the release rate was greatly decreased, and in simulated body fluid and intestinal fluid, the microcapsules exhibited a sustained release in 24 h with different release rates. The microspheres were characterized by Fourier transform infrared. The results suggested that the alginate/chitosan/starch microcapsules could be a suitable copolymeric carrier system for intestinal protein or peptides delivery in the intestine.     

Preparation and characterization of novel sinomenine microcapsules for oral controlled drug delivery

Background: Developing a sustained release drug to cure arthritis is needed. Sinomenine (SIN) is abstracted from sinomenium acutum and widely used in the treatment of various rheumatism and arrhythmia with few side effects. The primary aim of this study is to develop SIN microcapsules with polyelectrolyte multilayers for controlled drug release. Method: SIN microcrystals were encapsulated with chitosan, gelatin, and alginate by layer-by-layer technique, such as (gelatin/alginate)₄ and (chitosan/alginate)₆. The size distribution, zeta-potential, stability, and morphology of the microcapsules were characterized by a particle size analyzer, zetasizer, ultraviolet spectroscopy, and transmission electron microscope, respectively. The in vitro controlled release pattern of SIN was studied using a diffusion cell assembly at physiological pH of 6.8 or 1.4. Results: Light stability of these microcapsules was improved after microencapsulation. Compared with release rate of the SIN microcapsules coated by the poly(dimethyldiallyl ammonium chloride)/alginate and gelatin/alginate multilayers, release rate of the SIN microcapsules coated with chitosan/alginate multilayers was fast. Release rate progressively decreased with the increase of chitosan/alginate bilayer number and the decrease of pH value of release medium. Conclusion: These novel SIN microcapsules may be developed into oral controlled drug delivery for rheumatism and arthritis.     

Preparation of embolic NEMs loading capecitabine

The nanoparticles-embedded microcapsules (NEMs) with smooth surface, good sphericity, excellent dispersivity and uniform particle size distribution were prepared by emulsification combined with electrospraying to extend the sustained release performance of the embolic microcapsules loading capecitabine (CAP). The sodium alginate and chitosan with good biocompatibility were used as the materials and CAP as a small-molecule model drug. The drug loading, encapsulation efficiency and drug release of CAP in the NEMs were investigated. The results showed that the drug-loading and encapsulation efficiency both increased with the increment of chitosan and CAP concentration. The maximum values of drug loading and encapsulation efficiency were 1.97 and 18.01 % respectively when initial CAP concentration was 5.0 g/L and chitosan molecular weight 100 kDa. The cumulative release rate of CAP released from the NEMs was lower than 30 % in 0.5 h, which indicated that there was no obvious initial burst release behavior. In the subsequent 240 h, the release results confirmed that the NEMs had better sustained release properties compared to pure microcapsules, and it might be a new anticancer drug delivery system in the future studies.     

Development of modified in situ gelling oral liquid sustained release formulation of dextromethorphan

Context: Alternative strategies are being employed to develop liquid oral sustained release formulation. These included ion exchange resin, sustained release suspensions and in situ gelling systems. The later mainly utilizes alginate solutions that form gels upon contact with calcium which may be administered separately or included in the alginate solution as citrate complex. This complex liberates calcium in the stomach with subsequent gellation. The formed gel can break after gastric emptying leading to dose dumping.

Objective: Development of modified in situ gelling system which sustain dextromethorphan release in the stomach and intestine.

Methods: Solutions containing alginate with calcium chloride and sodium citrate were initially prepared to select the formulation sustaining the release in the stomach. The best formulation was combined with chitosan. All formulations were characterized with respect to flow, gelling capacity, gelling strength and drug release.

Results: Increasing the concentration of alginate increased the gelling capacity and strength and reduced the rate of drug release in gastric conditions with 2% w/v alginate being the best formulation. However, these formulations failed to sustain the release in the intestinal conditions. Incorporation of chitosan with alginate increased the gelling capacity and strength and reduced the rate of drug release compared to alginate only system. The effect was optimum in formulation containing 1.5% w/v chitosan. The sustained release pattern was maintained both in the gastric and intestinal conditions and was comparable to that obtained from the marketed product.

Conclusion: Alginate-chitosan based in situ gelling system is promising for developing liquid oral sustained release.     

Preparation,structural characterisation and release study of novel hybrid microspheres entrapping nanoselenium,produced by green synthesis

The main goal of this study was to synthesise and characterise different formulations based on alginate and alginate/chitosan microspheres containing nanoselenium (nano‐Se) for controlled delivery applications. Nanosize elemental selenium was produced by using probiotic yogurt bacteria (Lactobacillus casei) in a fermentation procedure. The structural and morphological characterisation of the microspheres was performed by Fourier transform infrared (FTIR), X‐ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. FTIR and XRD pattern indicated that was an effective cross‐linking of selenium nanoparticles within the polymeric matrix in both cases. The SEM images reveal that selenium nanoparticles are mainly exposed on the surface of alginate, in contrast to porous structure of alginate/chitosan/nano‐Se, interconnected in a regular network. This architecture type has a considerable importance in the delivery process, as demonstrated by differential pulse voltammetry. Selenium release from both matrices is pH sensitive. Moreover, chitosan blended with alginate minimise the release of encapsulated selenium, in simulated gastric fluid, and prolong the duration of release in intestinal fluid. The overall effect is the enhancement of total percentage release concomitant with the longer duration of action. The authors’ formulation based on alginate/chitosan is a convenient matrix to be used for selenium delivery in duodenum, caecum and colon.Inspec keywords: organic‐inorganic hybrid materials, nanocomposites, blending, filled polymers, nanoparticles, nanofabrication, nanomedicine, biomedical materials, drug delivery systems, microorganisms, biological organs, selenium, polymer blends, fermentation, scanning electron microscopy, X‐ray diffraction, Fourier transform infrared spectra, surface morphology, nanoporous materials, porosity, pH, voltammetry (chemical analysis), encapsulationOther keywords: structural characterisation, hybrid microspheres entrapping nanoselenium, green synthesis, alginate‐chitosan microspheres, controlled delivery applications, nanosize elemental selenium, probiotic yogurt bacteria, Lactobacillus casei, fermentation, scanning electron microscopy, morphological characterisation, SEM, Fourier transform infrared spectra, FTIR, XRD, X‐ray diffraction, selenium nanoparticles, polymeric matrix, porous structure, differential pulse voltammetry, pH, blending, encapsulated selenium, simulated gastric fluid, intestinal fluid, total percentage release concomitant, duodenum, caecum, colon, Se     

Preparation of alginate-gelatin capsules and its properties

Capsules based on alginate and gelatin prepared by extrusion method could increase the cell numbers of Lactobacillus casei ATCC 393 to be 10⁸ CFU·g^-1 in the wet state of the capsules. The capsules were spherical, smooth-surfaced and non-aggregated with a diameter of (4.0 ± 0.3) mm. The behavior of the samples were quite similar at low relative humidity (33%, 52%) and the ratio of weight change reached 93%. Four kinds of capsules in simulated gastric fluid (SGF) exhibited shrinkage while the beads eroded accompanied with slight swelling in simulated intestinal fluid (SIF). The pH values affected the stability of the capsules and with the increase in pH, the capsules changed from shrank then swelled and finally, broke into pieces. The capsules behaved differently under different ion intensities and the introduction of gelatin weakened the stability of capsules compared with the alginate ones. Cells of L. casei ATCC 393 could be continuously released from the capsules in the simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than those in SGF.     

Chitosan-alginate multilayer beads for gastric passage and controlled intestinal release of protein

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80-90% of the model protein within 12 h while multilayer beads released only 40-50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.     

Chitosan-Alginate Multilayer Beads for Gastric Passage and Controlled Intestinal Release of Protein

Abstract

Chitosan-alginate beads loaded with a model protein, bovine serum albumin (BSA) were investigated to explore the temporary protection of protein against acidic and enzymatic degradation during gastric passage. Optimum conditions were established for preparation of homogenous, spherical, and smooth chitosan-alginate beads loaded with BSA. Multilayer beads were prepared by additional treatment with either chitosan or alginate or both. The presence of chitosan in the coagulation bath during bead preparation resulted in increased entrapment of BSA. During incubation in simulated gastric fluid (SGF pH 1.2), the beads showed swelling and started to float but did not show any sign of erosion. Inclusion of pepsin in the gastric fluid did not show a further effect on the properties of the beads. Release studies were done in simulated gastric fluid (SGF pH 1.2) and subsequently in simulated intestinal fluid (SIF pH 7.5) to mimic the physiological gastrointestinal conditions. After transfer to intestinal fluid, the beads were found to erode, burst, and release the protein. Microscopic and macroscopic observations confirmed that the release of protein was brought about by the burst of beads. Chitosan-reinforced calcium-alginate beads showed delay in the release of BSA. The multilayer beads disintegrated very slowly. The enzymes pepsin and pancreatin did not change the characteristics of BSA-loaded chitosan-alginate beads. Single layer chitosan-alginate beads released 80–90% of the model protein within 12 h while multilayer beads released only 40–50% in the same period of time. The release from chitosan-alginate beads and multilayer beads in SIF was further delayed without prior incubation in SGF. It is concluded that alginate beads reinforced with chitosan offer an excellent perspective for controlled gastrointestinal passage of protein drugs.     

PSY-g-PAA/APT/SA载药复合凝胶小球的制备及释药性能

采用离子凝胶法制备了欧车前胶-g-聚丙烯酸/凹凸棒黏土/海藻酸钠(PSY-g-PAA/APT/SA)载药复合凝胶小球,以双氯芬酸钠为模型药物,考察了pH敏感性和凹凸棒黏土含量对凝胶小球的包封率、载药率、溶胀性能和药物释放行为的影响。结果表明,当释放介质为模拟胃液(pH=1.2)时,药物基本不释放;而为模拟肠液(pH=6.8)时,5h后累积释放率超过90%,复合凝胶小球具有明显的pH敏感性。随着凝胶小球中凹凸棒黏土含量的增加,溶胀率和药物累积释放率均减小,表明凹凸棒黏土的引入可以减缓药物的突释效应。     

Design and characterization of calcium-free in-situ gel formulation based on sodium alginate and chitosan

The aim of this study was to prepare and evaluate calcium-free sustained release drug delivery systems, based on the in-situ gelation of oral suspensions containing chitosan, sodium alginate and Ranitidine as drug model. The combined effects of polymer concentrations and their interactions on the rheological characteristics of both gels and suspensions and, on the kinetics of drug release were evaluated by using a central composite face-centered design. Rheological analysis showed that suspensions were potentially stable, with a viscosity increased by 1000 times compared to that of water. In addition, the obtained gels were consistent; their storage modulus could reach values close to 50?kPa when alginate concentration was greater than 7.5?g/100?mL and chitosan was fixed to 0.5?g/100?mL. In these conditions gels should have a higher gastric residence time, in comparison to the standard gastric emptying time (～2?h). Evaluation of the in-vitro release kinetics of Ranitidine showed that the association of the lowest concentration of chitosan (0.5?g/100?mL) with higher alginate concentrations generates sustained release kinetics profiles. The time corresponding to 63% of release was found close to 1.5?h, in which case the process is governed by Fickian diffusion. Finally, calcium-free alginate-chitosan based on the in-situ gelation of suspensions is advantageous as a drug delivery system for sustained-release.     

Formulation development and in-vitro/in-vivo correlation for a novel sterculia gum-based oral colon-targeted drug delivery system of azathioprine

The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6?h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T_max, prolonged absorption time, decreased C_max and absorption rate constant (K_a) indicating reduced systemic toxicity of the drug as compared to other dosage forms.     

疏水改性海藻酸钠衍生物包埋丁香油的释放性

目的通过化学方法将月桂醇与海藻酸钠接枝共聚形成两亲共聚物,对丁香油进行包埋形成微胶囊,使其具有一定的缓释性和良好的抗菌效果。方法利用两亲共聚物包埋丁香油形成包合物,采用单因素实验法,以包埋率为指标,评价月桂醇与海藻酸的接枝率对包埋率的影响,并在此基础上评价接枝率对缓释性以及不同环境下的稳定性和抗菌性能。结果在一定范围内包埋率随着接枝率的增大而升高;丁香油微胶囊的挥发率为14.11%,远低于丁香油的挥发率61.25%;释放试验中,丁香油微胶囊的缓释性明显优于未改性海藻酸纳,丁香油微胶囊能稳定缓慢地释放抗菌成分,控制大肠杆菌的生长。结论月桂醇改性海藻酸钠包埋丁香油形成的微胶囊具有一定的缓释和抗菌性能,突破了丁香油因挥发性强而存在的应用限制。     

Mucoadhesive alginate/poly (L-lysine)/thiolated alginate microcapsules for oral delivery of Lactobacillus salivarius 29

In this study, thiolated alginate was synthesized by introduction of cysteine to alginate to prepare mucoadhesive alginate/poly (L-lysine)/thiolated alginate (APTA) microcapsules for efficient oral delivery of Lactobacillus salivarius 29 (LS29), a novel therapeutic Lactobacillus strain, in vitro and in vivo. About 759 +/- 32.4 microM of cysteine per gram of alginate was introduced by estimation of Ellman's reagent reaction. LS29-loaded APTA microcapsules provided suitable morphology, size, and a high loading content and efficiency. LS29 in LS29-loaded APTA microcapsules were effectively protected from simulated gastric condition (pH 2.0) than that of unprotected LS29. LS29 were released from APTA microcapsules in simulated intestinal condition (pH 7.2) with a time-dependent manner. The in vitro and in vivo mucoadhesion study suggested that APTA microcapsules had remarkably stronger mucoadhesive property and provided a promising delivery system for oral administration of LS29.     

In Vitro/in Vivo Evaluation Of A Liquid Sustained Release Dosage Form Of Chlorpheniramine

Chlorpheniramine-resin complexes were coated with cellulose acetate butyrate to yield microcapsules with a geometric mean diameter of 346 μm. In vitro release rate of chlorpheniramine declined with increasing microcapsule size. Release of chlorpheniramine from the micropcapsules was faster in simulated gastric fluid (pH 1.2) than in simulated intestinal fluid (pH 7.5). A Chlorpheniramine solution administered by rapid intravenous injection to dogs exhibited a two phase decline in plasma drug concentration. A peroral solution resulted in a rapid rise to a peak followed by a sharp decline in plasma chlorpheniramine concentration. Peroral administration of a microcapsule suspension caused a rapid rise in plasma concentration, but prevented the fast decline.     

Preparation of alginate-gelatin capsules and its properties

Capsules based on alginate and gelatin prepared by extrusion method could increase the cell numbers of Lactobacillus casei ATCC 393 to be 10⁸ CFU·g⁻¹ in the wet state of the capsules. The capsules were spherical, smooth-surfaced and non-aggregated with a diameter of (4.0 ± 0.3) mm. The behavior of the samples were quite similar at low relative humidity (33%, 52%) and the ratio of weight change reached 93%. Four kinds of capsules in simulated gastric fluid (SGF) exhibited shrinkage while the beads eroded accompanied with slight swelling in simulated intestinal fluid (SIF). The pH values affected the stability of the capsules and with the increase in pH, the capsules changed from shrank then swelled and finally, broke into pieces. The capsules behaved differently under different ion intensities and the introduction of gelatin weakened the stability of capsules compared with the alginate ones. Cells of L. casei ATCC 393 could be continuously released from the capsules in the simulated gastrointestinal tract (GIT) and the release amounts and speeds in SIF were much higher and faster than those in SGF.     

Preparation of N-trimethyl chitosan-protein nanoparticles intended for vaccine delivery

In this paper, various N-trimethyl chitosan (TMC) of different molecular-weights (approximately 100 KD, approximately 200 KD, and approximately 400 KD, respectively) with the approximately degree of quartenization (DQ) of 40% were successfully synthesized. In vitro cytotoxicity of TMC solution showed the dependence of TMC concentration from 20 microg/ml to 500 microg/ml on the relative cell activity. Molecular weight of TMC did not greatly affect the cytotoxicity of TMC against HEK293 and L929 cells. TMC nanoparticles and alginate modified TMC nanoparticles were prepared by the ionic gelation method. Subsequently, we investigated the properties of TMC nanoparticles and alginate modified TMC nanoparticles intending for oral delivery of antigens. Molecular weight of TMC did not affect the loading capacity (LC) and in vitro release behavior of TMC nanoparticles. However, BSA concentration and alginate modification have strongly effect on properties of TMC nanoparticles (particle size; surface charge; loading efficiency and loading capacity). In vitro release behavior indicated that alginate modification could efficiently decrease initial burst release and extend release time in phosphate buffer (PBS, pH 7.4) and acidic solution (0.1 M HCl, pH = 1) at 37 degrees C. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) assay showed that alginate modification could effectively improve the stability of TMC nanoparticles and protect BSA from degradation or hydrolysis in acidic condition for at least 2 h.     

Preparation and Evaluation Of Drug-Containing Chitosan Beads

Abstract

Sulfadiazine beads were prepared by dropping drug-containing solutions of the positively charged polysaccharide, chitosan, into tripolyphosphate (TPP) solutions. The droplets instantaneously formed gelled spheres by ionotropic gelation, entrapping the drug within a three-dimensional network of the ionically linked polymer. To achieve maximum drug content, high payloads, short gelation times, low TPP concentrations, and a low internal to external phase ratio were required. The chitosan beads showed pH-dependent swelling and dissolution behavior. The beads swelled and dissolved in 0.1N HCl, while they stayed intact in simulated intestinal fluid. The release of sulfadiazine in 0.1N HCl decreased with increasing concentration of TPP, but was independent of the TPP concentration in intestinal fluids. The morphology of the beads was investigated by scanning electron microscopy. The porosity of the beads depended on the method of drying.     

Preparation and Evaluation Of Drug-Containing Chitosan Beads

Sulfadiazine beads were prepared by dropping drug-containing solutions of the positively charged polysaccharide, chitosan, into tripolyphosphate (TPP) solutions. The droplets instantaneously formed gelled spheres by ionotropic gelation, entrapping the drug within a three-dimensional network of the ionically linked polymer. To achieve maximum drug content, high payloads, short gelation times, low TPP concentrations, and a low internal to external phase ratio were required. The chitosan beads showed pH-dependent swelling and dissolution behavior. The beads swelled and dissolved in 0.1N HCl, while they stayed intact in simulated intestinal fluid. The release of sulfadiazine in 0.1N HCl decreased with increasing concentration of TPP, but was independent of the TPP concentration in intestinal fluids. The morphology of the beads was investigated by scanning electron microscopy. The porosity of the beads depended on the method of drying.     

In Vitro/in Vivo Evaluation Of A Liquid Sustained Release Dosage Form Of Chlorpheniramine

Abstract

Chlorpheniramine-resin complexes were coated with cellulose acetate butyrate to yield microcapsules with a geometric mean diameter of 346 μm. In vitro release rate of chlorpheniramine declined with increasing microcapsule size. Release of chlorpheniramine from the micropcapsules was faster in simulated gastric fluid (pH 1.2) than in simulated intestinal fluid (pH 7.5). A Chlorpheniramine solution administered by rapid intravenous injection to dogs exhibited a two phase decline in plasma drug concentration. A peroral solution resulted in a rapid rise to a peak followed by a sharp decline in plasma chlorpheniramine concentration. Peroral administration of a microcapsule suspension caused a rapid rise in plasma concentration, but prevented the fast decline.     

Microencapsulation by Emulsion Non-Solvent Additicin Method

Cellulose acetate butyrate microcapsules containing propranolol were prepared by emulsion non-solvent addition method. The effects on drug release of different polyethylene glycols (PEG), various concentrations of PEG 4000, and particle size of the drug to be encapsulated were investigated. In vitro dissolution of microcapsules in simulated intestinal fluid and buffers at different pH was also studied. PEGs were found to increase drug release for this system. The pH dissolution profiles of the microcapsules indicated that dissolution was slightly pH dependent during the first 8 hours of dissolution.