Preparation and characterization of Ganoderma lucidum spores-loaded alginate microspheres by electrospraying (2025)

Production of Ganoderma Lucidum Extract Loaded Gelatin-Sodium Alginate Microspheres, Investigation of Release Kinetics at Different pH Values and Evalution of Kinetic Models

Mugla Journal of Science and Technology

In this study, pH sensitive microsphere polymeric drug carriers were produced by using biodegradable natural gelatin and sodium alginate polymers. Microspheres were loaded with prepared Ganoderma lucidum extract that is a medicinal mushroom and has the potential to be used in several diseases' treatment. Extract release kinetics of the microspheres were examined by spectrophotometric method by using an UV spectrometer. Buffer solutions with different pH values were used as release medium for examination of drug release kinetics of the produced microspheres. The Ganoderma lucidum release of microspheres was presented in terms of percent cumulative release (CR%) defined as the percentage ratio of the instantaneous amount of Ganoderma lucidum released at a certain time of incubation to the initial amount of Ganoderma lucidum loadings. As a result, it was seen that the release of the extract accelerated as pH of the release medium increased and the fastest extract release was observed in the pH 7. The release kinetic models of the microspheres were examined. The release kinetics of microspheres fitted Higuchi model for pH 1.3, pH 5.0 and pH 6.0 and first-order model for pH 3.0 and pH 7.0.

Influence of Sodium Alginate Concentration on Microcapsules Properties Foreseeing the Protection and Controlled Release of Bioactive Substances

Journal of Chemistry, 2021

To understand the abilities of Ca-alginate microcapsules and their specific applications in different fields, it is necessary to determine the physicochemical and structural properties of those formulated microcapsules. In this work, we aimed to study the effect of alginate concentration in the improvement of the encapsulation efficiency (EE) and on the release of phenolic and flavonoid substances. The relationship between the structure of the encapsulated bioactive substance and Ca-alginate network and their effect on the EE and release kinetics have been investigated. The incorporation, structure, morphology, and phase properties of all elaborated materials were characterized by UV-spectroscopy, Fourier transform infrared (ATR-FTIR), scanning electron microscope (SEM), and X-ray diffraction (DRX). The results indicate that increasing the polymer concentration increases the EE and decreases the loading capacity (LC), whereas the effect of alginate polymer concentration on the relea...

Influence of surface morphology and structure of alginate microparticles on the bioactive agents release behavior

Carbohydrate Polymers, 2019

The structure-property relationship in alginate microparticles (microspheres and microcapsules prepared with or without Trichoderma viride spores (Tv) was investigated. Surface morphology, structure and release behavior from alginate microparticles strongly depend on calcium concentration and presence of Tv and chitosan layer. All microparticles exhibited a granular surface structure with substructures consisting of abundant smaller particles. In vitro active agents release study revealed that the increase in calcium cation concentration reduced the release rate of Tv (˜84% for microspheres;˜57% for microcapsules) and calcium cations (˜20% for microspheres;˜23% for microcapsules). The average decrease in k values due to chitosan layer addition is 41% for Tv and 93% for calcium ions, respectively. The underlying Tv release mechanism from microspheres is anomalous transport kinetics, whereas from microcapsules is controlled by Type II transport. The differences in microparticle surface properties did not affect the mechanism controlling calcium ions release detected as diffusion through microparticles.

Preparation and Characteristics of Alginate Microparticles for Food, Pharmaceutical and Cosmetic Applications

Polymers

Alginates are the most widely used natural polymers in the pharmaceutical, food and cosmetic industries. Usually, they are applied as a thickening, gel-forming and stabilizing agent. Moreover, the alginate-based formulations such as matrices, membranes, nanospheres or microcapsules are often used as delivery systems. Alginate microparticles (AMP) are biocompatible, biodegradable and nontoxic carriers, applied to encapsulate hydrophilic active substances, including probiotics. Here, we report the methods most frequently used for AMP production and encapsulation of different actives. The technological parameters important in the process of AMP preparation, such as alginate concentration, the type and concentration of other reagents (cross-linking agents, oils, emulsifiers and pH regulators), agitation speed or cross-linking time, are reviewed. Furthermore, the advantages and disadvantages of alginate microparticles as delivery systems are discussed, and an overview of the active ingre...

Chitosan-Coated Alginate Microcapsules Loaded with Herbal galactagogue Extract: Formulation Optimization and Characterization

2019

Many herbs and spices have been recommended traditionally as galactagogues and several commercial formulations prepared using herbs. Due to the presence of various compounds such as polyphenols, flavonoids, isoflavones, and terpenes, bitter and stringent taste is elicited that make the consumption of these herbal preparations unpleasant. Moreover, these compounds are unstable when exposed to environmental conditions. In this regard, different approaches are used for taste masking such as microencapsulation. In the present study, microcapsules containing herbal galactagogue extract were developed through emulsification/external gelation and Box-Behnken design was used to investigate the effects of independent variables (sodium alginate: 1-1.5%, calcium chloride: 0.2-1% and extract concentrations: 1-5%) on encapsulation efficiency (EE%). Following evaluation of the model, the optimum condition of encapsulation process was selected as 1.49% sodium alginate, 0.84 CaCl2, and 1.58% extrac...

Design, optimization and characterization of glutathione loaded- alginate microspheres for topical antiaging [Diseño, optimización y caracterización de microesferas de glutatión cargado de alginato para el antienvejecimiento tópico]

2019

Context: Glutathione in the reduced form (GSH) is the predominant intracellular form, which acts as a strong antioxidant. However, it has low skin permeability due to the high hydrophilicity. Hence, the objective of this study was to prepare GSH by using microspheres delivery system and adding surfactant to overcome the barrier function of the skin. Aims: To investigate the effect of polymer and surfactant on the characteristics and release profile of GSH-alginate microspheres. Methods: GSH-alginate microspheres were prepared using ionotropic gelation method by aerosolisation. A randomized full factorial design was applied to prepare four different formulations of glutathione loaded alginate microspheres. Design was applied for all formulations to study about effect of independent variables of polymer and crosslinker on the entrapment efficiency (EE), drug loading (DL), particle size, yield, and in vitro drug release profile. For release study, microspheres formulas were also compared to microspheres, which applied into gel base. Results: The GSH-alginate microspheres had a high EE ranging from 34.74 ± 0.07% to 56.63 ± 0.36%, with small particle sizes ranging from 1.89 ± 0.03 µm to 2.42 ± 0.08 µm, and drug loading ranging from 5.72 ± 0.05% to 6.23 ± 0.02%. The kinetic analysis of all release profiles was found to follow Higuchi's diffusion model. EE, DL, particle size, and yield variables had a significant effect on the dependent variables (p<0.05), and flux had no significant effect on the dependent variables (p>0.05). Conclusions: All formulas produced high yield and encapsulation efficiency and small size particles. From the 2 2 randomized full factorial design, there was showed that the combination of the use of surfactant and polymer concentration significantly affected DL and EE.

Alginates and similar exopolysaccharides in biomedical application and pharmacy: Controled delivery of drugs

Advanced technologies, 2016

Due to its biocompatibility, biodegradability, hydrophility, technological properties and vast availability, polysaccharides are widely used as natural non-toxic polymers in different branches of industry (food, cosmetic, textile, construction industries). Exopolysaccharides (as dextran, pullulan) have recently taken up a significant position in pharmaceutical industry. Alginate has an irreplaceable role in biomedicine, since its hydrogel form is successfully applied for immobilization of a wide range of enzymes, therapeutics, biochemical agents and different kinds of microorganisms and cells (herbal, animal or human). Alginate microspheres and microcapsules are used for controlled release of biologically active molecules, as well as cell carriers in tissue engineering. Special benefits are brought by the simplicity of configuration of alginate hydrogel, including the possibility of the controlled production of micro-and nanoparticles. Taking into account a very important role of alginates in the form of hydrogel in biomedicine, in this paper a specific attention is paid on the preparation and application of alginate matrices, microspheres and microcapsules that may have essential and unexchangeable usage/application. This paper therefore displays various possibilities of use of polysaccharide matrices for biomolecules, polysaccharide as excipients of pharmaceutical products for oral or local application, and provides a review of the examples of innovative applications.

Sodium Alginate—Natural Microencapsulation Material of Polymeric Microparticles

International Journal of Molecular Sciences

From the multitude of materials currently available on the market that can be used in the development of microparticles, sodium alginate has become one of the most studied natural anionic polymers that can be included in controlled-release pharmaceutical systems alongside other polymers due to its low cost, low toxicity, biocompatibility, biodegradability and gelatinous die-forming capacity in the presence of Ca2+ ions. In this review, we have shown that through coacervation, the particulate systems for the dispensing of drugs consisting of natural polymers are nontoxic, allowing the repeated administration of medicinal substances and the protection of better the medicinal substances from degradation, which can increase the capture capacity of the drug and extend its release from the pharmaceutical form.

Alginate microspheres prepared by internal gelation: Development and effect on insulin stability

International Journal of Pharmaceutics, 2006

Recombinant human insulin was encapsulated within alginate microspheres by the emulsification/internal gelation technique with the objective of preserving protein stability during encapsulation procedure. The influence of process and formulation parameters was evaluated on the morphology and encapsulation efficiency of insulin. The in vitro release of insulin from microspheres was studied under simulated gastrointestinal conditions and the in vivo activity of protein after processing was assessed by subcutaneous administration of extracted insulin from microspheres to streptozotocin-induced diabetic rats. Microspheres mean diameter, ranging from 21 to 287 m, decreased with the internal phase ratio, emulsifier concentration, mixer rotational speed and increased with alginate concentration. Insulin encapsulation efficiency, near 75%, was not affected by emulsifier concentration, mixer rotational speed and zinc/insulin hexamer molar ratio but decreased either by increasing internal phase ratio and calcium/alginate mass ratio or by decreasing acid/calcium molar ratio and alginate concentration. A high insulin release, above 75%, was obtained at pH 1.2 and under simulated intestinal pH a complete dissolution of microspheres occurred. Extracted insulin from microspheres decreased hyperglycemia of diabetic rats proving to be bioactive and showing that encapsulation in alginate microspheres using the emulsification/internal gelation is an appropriate method for protein encapsulation.

Synthesis of quercetin-encapsulated alginate beads with their antioxidant and release kinetic studies

Journal of Macromolecular Science, Part A, 2020

In this present study, different forms of quercetin encapsulated beads were synthesized, namely ionic cross-linked gel beads and cryogel beads. Fourier Transform Infrared (FT-IR) spectra of the beads were used to characterize and prove quercetin encapsulation in alginate beads. Swelling and drying profiles were studied. Besides, release kinetics of quercetin molecules from gel beads and cryogels were carefully investigated in two different solvent/media; dimethyl sulfoxide (DMSO) and Roswell Park Memorial Institute Medium (RPMI-1640). Based upon the release kinetic studies, it is found that quercetin release from alginate cryogel beads fits the first-order release model in DMSO and it depends on the concentration of quercetin in the beads. The release of quercetin from alginate gel beads was described by the Higuchi release model, which highlights the release of quercetin molecules through the pores of the matrix. In RPMI-1640, the release of quercetin from both forms of alginate beads fits zero-order release model and it indicates a constant release of quercetin per unit time. Finally, the radical scavenging activity of the quercetin quantities was tested by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test, and successful results were obtained compared to reference material.

Surprising performance of alginate beads for the release of low-molecular-weight drugs

Journal of Applied Polymer Science, 2010

The model of low-molecular-weight drugs has been encapsulated within alginate beads hardened with calcium chloride. The drug's release kinetic using 3% (w/v) alginate has shown a surprising behavior after 2 h, where the release kinetic was shifted from Fickian to case II transport mechanism contradicting other authors like Akihiko et al. (J Control Release 1999, 58, 21). To support this finding, we studied the swelling of dried gel beads of 2 and 3% (w/v) alginate, which showed a sudden decrease in the swelling of 3% (w/v) alginate after 2 h due to a partial bursting of the beads. This sudden bursting was clearly observed using the optical microscope to emphasize the new findings. Calcium alginate beads revealed pH sensitivity, where 2% (w/v) alginate beads showed a maximum swelling of 5000% in alkaline medium at pH 7.4, compared with a negligible swelling percent of 60% in acidic medium (pH 1.2). Accordingly, it could be a good candidate for targeting smart and low-molecular-weight drugs to the intestine.

Insulin-loaded alginate microspheres for oral delivery-Effect of polysaccharide reinforcement on physicochemical properties and release profile

Carbohydrate polymers, 2007

Oral administration of insulin requires protein protection from degradation in the gastric environment and its absorption improvement in the intestinal tract. To achieve this objective several types of microspheres composed of alginate, chitosan and dextran sulphate have been prepared by ionotropic gelation. Parameters such as the mean particle size, swelling behaviour, insulin encapsulation efficiency, loading capacity and release profiles in simulated gastric and intestinal fluids have been compared for the systems developed. In this study, attempts have been made to increase insulin protection and to improve its release from microspheres by reinforcing the alginate matrix with chitosan and/or dextran sulphate. Dextran sulphate was able to avoid insulin release at pH 1.2, protecting the protein from the acidic environment and reducing the total insulin released at pH 6.8. This effect was explained by an interaction between the permanent negatively charged groups of dextran sulphate and insulin molecules.

Preparation and characterization of alginate microspheres containing a model antigen

In development of controlled release formulations, microspheres play a vital role. Alginate microspheres are easy to prepare in lab scale. Present study is focused on the study of effect of different types and concentration of cross linking agents in the alginate microspheres prepared using ionic gelation technique. Paracetamol was used as a model drug for the study. Prepared microspheres were subjected to various evaluation parameters including drug content, bulk density and tap density, angle of repose, Carr's index, Hausner's ratio and in vitro dissolution study. Results concluded that the microspheres prepared with BaCl 2 showed good per cent drug content, good flow properties as well as good per cent drug release as compared to the formulations prepared with CaCl 2 . All formulations had Hausner's Ratio <1.00 which shows a good flow property and compressibility index about ≤10%. Angle of repose for all the formulation had <20 ɸ which states the low cohesion forces and frictional coefficient between particles. An average range for drug release from all formulations at the end of 21st hour was found to be in range of 60 to 80%. In particular lower per cent (5%) of crosslinking agent (in formulation B1) was favourable for ensuring good drug content, good flow properties and good per cent drug release.

Calcium phosphate-alginate microspheres as enzyme delivery matrices

Biomaterials, 2004

The present study concerns the preparation and initial characterisation of nov el calcium titanium phosphate-alginate (CTPalginate) and hydroxyapatite-alginate (HAp-alginate) microspheres, which are intended to be used as enzyme delivery matrices and bone regeneration templates. Microspheres were prepared using different concentrations of polymer solution (1% and 3% w/v) and different ceramic-to-polymer solution ratios (0.1, 0.2 and 0.4 w/w). Ceramic powders were characterised using X-ray diffraction, laser granulometry, Brunauer, Emmel and Teller (BET) method for the determination of surface area, zeta potential and Fourier transform infrared spectroscopy (FT-IR). Alginate was characterised using high performance size exclusion chromatography. The methodology followed in this investigation enabled the preparation of homogeneous microspheres with a uniform size. Studies on the immobilisation and release of the therapeutic enzyme glucocerebrosidase, employed in the treatment of Gaucher disease, were also performed. The enzyme was incorporated into the ceramic-alginate matrix before gel formation in two different ways: preadsorbed onto the ceramic particles or dispersed in the polymeric matrix. The two strategies resulted in distinct release profiles. Slow release was obtained after adsorption of the enzyme to the ceramic powders, prior to preparation of the microspheres. An initial fast release was achiev ed when the enzyme and the ceramic particles were dispersed in the alginate solution before producing the microspheres. The latter profile is very similar to that of alginate microspheres. The different patterns of enzyme release increase the range of possible applications of the system inv estigated in this work.

Formation and characterization of pDNA-loaded alginate microspheres for oral administration in mice

Journal of Bioscience and Bioengineering, 2012

Alginate, a natural polysaccharide, was explored in this study as an oral delivery vehicle of a mammalian expression vector into the murine intestinal mucosa. Alginate microspheres were produced through water-in-oil (W/O) emulsification method. Average diameter sizes of microspheres were 46.88 μm ± 3.07 μm with significant size reduction upon utilization of 1.0% Span80. Plasmid DNA (pDNA) carrying green fluorescent protein reporter gene (GFP), pVAX-GFP, was encapsulated within microspheres at efficiencies of 72.9 to 74.4%, carrying maximum load of 6 μg pDNA. Alginate microspheres demonstrated shrinkage in pH 1.2 and swelling in pH 9.0 with pDNA release about twice the amount released in acidic environment. Oral delivery of pVAX-GFP loaded-microspheres, at 50 μg, 100 μg and 150 μg dose, was performed on BALB/c mice. Tissue biodistribution, investigated through flow cytometric analysis, demonstrated GFP positive intestinal cells (b 1.0%) with 1.3-fold higher levels for the 100 μg dose; therefore suggesting feasibility of the approach for oral gene delivery and vaccination.

Formulation and in vitro characterization of alginate microspheres loaded with diloxanide furoate for colon- specific drug delivery

Asian Journal of Pharmaceutics, 2010

T he aim of the research work was to develop cyst-targeted alginates microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Calcium alginates microspheres of DF were prepared using emulsification method using calcium chloride as a cross-linking agent. Alginate is a natural polysaccharide found in brown algae. Alginates are widely used in the food and pharmaceutical industries and have been employed as a matrix for the entrapment of drugs, macromolecules and biological cells. Alginate microspheres produced by the emulsification method using calcium chloride. Formulations were characterized for particle size and shape, surface morphology, entrapment efficiency, and in vitro drug release in simulated gastrointestinal fluids. XRD and differential scanning calorimetery were used to confirm successful entrapment of DF into the alginates microspheres. All the microsphere formulations showed good % drug entrapment (73.82±1.99). Calcium alginate retarded the release of DF at low pH (1.2 and 4.5) and released microspheres slowly at pH 7.4 in the colon without colonic enzymes.

Design, optimization and characterization of glutathione loaded-alginate microspheres for topical antiaging

Journal of Pharmacy & Pharmacognosy Research, 2019

Context: Glutathione in the reduced form (GSH) is the predominant intracellular form, which acts as a strong antioxidant. However, it has low skin permeability due to the high hydrophilicity. Hence, the objective of this study was to prepare GSH by using microspheres delivery system and adding surfactant to overcome the barrier function of the skin. Aims: To investigate the effect of polymer and surfactant on the characteristics and release profile of GSH–alginate microspheres. Methods: GSH-alginate microspheres were prepared using ionotropic gelation method by aerosolisation. A randomized full factorial design was applied to prepare four different formulations of glutathione loaded alginate microspheres. Design was applied for all formulations to study about effect of independent variables of polymer and crosslinker on the entrapment efficiency (EE), drug loading (DL), particle size, yield, and in vitro drug release profile. For release study, microspheres formulas were also compared to microspheres, which applied into gel base. Results: The GSH-alginate microspheres had a high EE ranging from 34.74 ± 0.07% to 56.63 ± 0.36%, with small particle sizes ranging from 1.89 ± 0.03 µm to 2.42 ± 0.08 µm, and drug loading ranging from 5.72 ± 0.05% to 6.23 ± 0.02%. The kinetic analysis of all release profiles was found to follow Higuchi’s diffusion model. EE, DL, particle size, and yield variables had a significant effect on the dependent variables (p<0.05), and flux had no significant effect on the dependent variables (p>0.05). Conclusions: All formulas produced high yield and encapsulation efficiency and small size particles. From the 22 randomized full factorial design, there was showed that the combination of the use of surfactant and polymer concentration significantly affected DL and EE.

Biologically triggered liberation of sub-micron particles from alginate microcapsules

Journal of Materials Chemistry B, 2013

A new method for triggering the burst liberation of encapsulated sub-micron particles from carrier particles using embedded microorganisms has been developed. Triggering mechanisms such as those based on chemical, light, thermal, or magnetic stimuli are known, but man-made particles are not yet able to replicate the concept of "dormancy" found in biological systems in the form of spores or seeds that survive in an inactive state and start to grow only once favourable environmental conditions are encountered. An engineered particle system that mimics this property by embedding viable yeast cells into synthetically made alginate microcapsules is reported in the present work. Cell growth and division is used as a triggering mechanism for stimuli-responsive release of the encapsulated content. The hybrid living/artificial capsules were formed by an inkjet printing process and the mechanism of biologically triggered release was shown using fluorescently labelled liposomes.

Microcapsules made by enzymatically tailored alginate

Journal of Biomedical Materials Research, 2003

Alginate is widely used for encapsulation of cells. Alginate is a linear block copolymer consisting of mannuronic acid (M) and guluronic acid (G). It has been shown that enzymes known as C-5 epimerases convert M to G in the polymer chain, giving rise to novel alginates with tailored properties. One of these enzymes, AlgE4, converts M blocks into blocks of strictly alternating M and G. In this study we investigated how alginate epimerized by AlgE4 affected capsule properties such as stability and permeability. Inhomogeneous calcium-alginate gel beads were made with original and AlgE4-epimerized alginates of different origin. The epimerized alginates formed initially smaller alginate gels that showed increased resistance to osmotic swelling compared with the original nonmodified alginate samples. The permeability, measured as diffusion of immunoglobulin (Ig) G into Ca/Ba-alginate gel beads, was reduced by epimerization and further reduced by addition of poly-L-lysine (PLL). The osmotic stability of alginate-poly-D-lysine(PDL)-alginate capsules was enhanced by the use of epimerized alginate; indeed, stable capsules with low permeability to tumor necrosis factor (TNF) could be made with low PDL exposures. Finally, alginate with an alternating structure interacted more strongly with the alginate-PLL capsule than did alginate with a high content of M blocks or G blocks or than an alginate consisting mainly of M.

Novel thermosensitive calcium alginate microspheres: Physico-chemical characterization and delivery properties

Acta Biomaterialia, 2010

The system described in this paper was obtained by soaking calcium alginate (CaAlg) microspheres in a water solution of poly-[(3-acrylamidopropyl)-trimethylammonium chloride-b-N-isopropylacrylamide] [poly(AMPTMA-b-NIPAAM)], a new block co-polymer recently synthesized by atom transfer radical polymerization (ATRP). The block co-polymer is characterized by a lower critical solution temperature (LCST) of 41°C in aqueous 0.1 M NaCl solution, and can be anchored on the CaAlg microspheres by means of polyion interactions. Polycations (permanently positively charged blocks) and polyanions (free alginate carboxylic groups) interact, leading to microspheres with thermosensitive properties. As an effect of interaction with the microspheres the LCST of the co-polymer is lowered to 36-38°C. In this temperature range a colloidal water suspension of the microspheres collapses, forming macroscopic aggregates. The new system shows, at human body temperature, an improved ability to carry and deliver both hydrophobic and hydrophilic molecules in comparison with unmodified CaAlg microspheres. The release properties of the microspheres loaded with different model drugs can be appropriately modulated by the amount of the poly(AMPTMA-b-NIPAAM). Furthermore, the microspheres show the interesting capability of retaining the activity of a loaded enzyme (horseradish peroxidase), used as a model protein. The results obtained indicate that the proposed drug delivery system may be suitable for drug depot applications.