Differential role of microenvironment in microencapsulation for improved cell tolerance to stress

The effect of the microenvironment in alginate–chitosan–alginate (ACA) microcapsules with liquid core (LCM) and solid core (SCM) on the physiology and stress tolerance of Sacchromyces cerevisiae was studied. The suspended cells were used as control. Cells cultured in liquid core microcapsules showed a nearly twofold increase in the intracellular glycerol content, trehalose content, and the superoxide dismutase (SOD) activity, which are stress tolerance substances, while SCM did not cause the significant physiological variation. In accordance with the physiological modification after being challenged with osmotic stress (NaCl), oxidative stress (H₂O₂), ethanol stress, and heat shock stress, the cell survival in LCM was increased. However, SCM can only protect the cells from damaging under ethanol stress. Cells released from LCM were more resistant to hyperosmotic stress, oxidative stress, and heat shock stress than cells liberated from SCM. Based on reasonable analysis, a method was established to estimate the effect of microenvironment of LCM and SCM on the protection of cells against stress factors. It was found that the resistance of LCM to hyperosmotic stress, oxidative stress, and heat shock stress mainly depend on the domestication effect of LCM’s microenvironment. The physical barrier of LCM constituted by alginate–chitosan membrane and liquid alginate matrix separated the cells from the damage of oxidative stress and ethanol stress. The significant tolerance against ethanol stress of SCM attributed to the physical barrier consists of solid alginate–calcium matrix and alginate–chitosan membrane.     

渗透压敏感和耐高渗酵母菌在海藻酸钠-壳聚糖-海藻酸钠微囊中的生长和代谢

为了研究微囊微环境中渗透压对微囊内不同渗透压敏感性细胞生长、代谢的影响, 分别以渗透压敏感型酿酒酵母Y02724与耐高渗酵母Hansel为细胞模型, 考察了有氧条件下这两种细胞在海藻酸钠-壳聚糖-海藻酸(Alginate-chitosan-alginate, ACA)微胶囊中的生长、代谢状态。主要检测了细胞比生长速率、最大产物生成量以及代谢物乙醇、甘油分泌量等的变化。实验结果分析表明, 渗透压胁迫可能是导致不同渗透压敏感性细胞在微囊微环境中生长代谢特征变化的因素之一, 即微囊微环境内可能存在渗透压胁迫。     

Metabolic response of different osmo-sensitive Sacchromyces cerevisiae to ACA microcapsule

Microencapsulation technology is a convenient method to alter and regulate cell product formation. In order to probe the metabolic response of different osmo-sensitive Sacchromyces cerevisiae to ACA microcapsule, the hyper-osmo-sensitive type S. cerevisiae (Y02724) and wild type S. cerevisiae (BY4741) were encapsulated into liquid core ACA microcapsules. The behavior of cell growth, glucose consumption, ethanol production and the yields of glycerol and organic acids were determined. Free cell culture was used as control. The enzyme activities of NADP⁺-glutamate dehydrogenase (GDH), glutamine synthetase (GS) and glutamate synthase (GOGAT) on microencapsulation cells and free cultured cells were measured too. The results demonstrated that the growth of Y02724 in both aerobic and anaerobic conditions was seriously inhibited by ACA microcapsule, while the ethanol and acetatic acid yield of microencapsulation Y02724 in anaerobic condition were significantly higher than that of suspended cultivation. For Y02724, the microencapsulation cultivation significantly increased the GS and GOGAT activities and decreased the GDH activity in comparison with control group. ACA microcapsules did not significantly change the growth behavior and metabolic performance of BY4741, but decreased the GS activity. In conclusion, microcapsules microenvironment significantly changes the metabolism behavior of hyper-osmo-sensitive type S. cerevisiae (Y02724), but nearly had no effect on BY4741.     

Preparation and characterization of novel polymeric microcapsules for live cell encapsulation and therapy

This article describes the preparation and in vitro characterization of novel genipin cross-linked alginate-chitosan (GCAC) microcapsules that have potential for live cell therapy applications. This microcapsule system, consisting of an alginate core with a covalently cross-linked chitosan membrane, was formed via ionotropic gelation between calcium ions and alginate, followed by chitosan coating by polyelectrolyte complexation and covalent cross-linking of chitosan by naturally derived genipin. Results showed that, using this design concept and the three-step procedure, spherical GCAC microcapsules with improved membrane strength, suppressed capsular swelling, and suitable permeability can be prepared. The suitability of this novel membrane formulation for live cell encapsulation was evaluated, using bacterial Lactobacillus plantarum 80 (pCBH1) (LP80) and mammalian HepG2 as model cells. Results showed that capsular integrity and bacterial cell viability were sustained 6 mo postencapsulation, suggesting the feasibility of using this microcapsule formulation for live bacterial cell encapsulation. The metabolic activity of the encapsulated HepG2 was also investigated. Results suggested the potential capacity of this GCAC microcapsule in cell therapy and the control of cell signaling; however, further research is required.     

Growth of recombinant fibroblasts in alginate microcapsules

To develop a novel strategy of nonautologous somatic gene therapy, we now demonstrate the feasibility of culturing genetically modified fibroblasts within an immunoprotective environment and the optimal conditions required for their continued survival in vitro. When mouse Ltk(-) fibroblasts transfected with the human growth hormone gene were enclosed within permselective microcapsules fabricated from alginate-polylysine-alginate, they continued to secrete human growth hormone at the same rates as the nonencapsulated cells. They also continued to proliferate in vitro for at least 1 month even though their viability gradually declined to about 50%. The viability can be improved by controlling for (a) temperature during encapsulation, (b) duration of treatment with polylysine, (c) duration of liquefying the core alginate with sodium citrate, and (d) cell density at the time of encapsulation. The best conditions leading to improved survival and maximum proliferation of cells within the microcapsules were obtained by encapsulating the cells at 4 to 10 degrees C instead of room temperature, coating the microspheres with polylysine for 6 to 10 min instead of 20 min, liquefying the core alginate by treating with citrate for 20 min instead of 6 to 10 min, and using a concentration of 2 x 10(6) cells/mL of alginate for encapsulation. Under such conditions, normally adherent and genetically engineered mouse fibroblasts survived and proliferated optimally within the microcapsule environment. The encapsulated fibroblasts maintained their level of transgene expression while recombinant gene products such as human growth hormone could diffuse through the microcapsule membrane without impediment. The demonstration that genetically modified fibroblasts can survive and continue to deliver recombinant gene products from within these microcapsules and the optimization for their maximal viability and growth within microcapsules should increase the potential for success in using such microencapsulated recombinant cells for somatic gene therapy. (c) 1994 John Wiley & Sons, Inc.     

表达耐辐射异常球菌IrrE蛋白对产丁二酸大肠杆菌耐渗透压的影响

高渗透压胁迫是降低生物法制备丁二酸生产效率的关键因素之一。为提高丁二酸生产菌株对高渗透压胁迫的耐受性能,本研究考察了外源引入全局调控蛋白IrrE提高大肠杆菌耐高渗透压胁迫性能的可行性。试验结果表明,在不同浓度Na+胁迫下,重组菌生长和发酵性能明显提升。在5 L罐发酵中,重组菌最大细胞干重、糖耗和丁二酸产量比对照菌分别提高了15.6%、22%和23%,表明引入IrrE蛋白可提高菌株对高渗透压胁迫的耐受能力。进一步比较重组菌和对照菌胞内相容性物质海藻糖和甘油的浓度后发现,重组菌胞内海藻糖和甘油浓度明显提高,其最大积累量分别是对照菌的1.3和3.8倍,推测IrrE可通过增加胞内相容性物质的积累提高菌株对高渗透压胁迫的耐受性。     

CHO immobilization in alginate/poly-l-lysine microcapsules: an understanding of potential and limitations

Microencapsulation offers a unique potential for high cell density, high productivity mammalian cell cultures. However, for successful exploitation there is the need for microcapsules of defined size, properties and mechanical stability. Four types of alginate/poly-l-Lysine microcapsules, containing recombinant CHO cells, have been investigated: (a) 800 μm liquid core microcapsules, (b) 500 μm liquid core microcapsules, (c) 880 μm liquid core microcapsules with a double PLL membrane and (d) 740 μm semi-liquid core microcapsules. With encapsulated cells a reduced growth rate was observed, however this was accompanied by a 2–3 fold higher specific production rate of the recombinant protein. Interestingly, the maximal intracapsular cell concentration was only 8.7 × 10⁷ cell mL^-1, corresponding to a colonization of 20% of the microcapsule volume. The low level of colonization is unlikely to be due to diffusional limitations since reduction of microcapsule size had no effect. Measurement of cell leaching and mechanical properties showed that liquid core microcapsules are not suitable for continuous long-term cultures (>1 month). By contrast semi-liquid core microcapsules were stable over long periods with a constant level of cell colonization (ϕ = 3%). This indicates that the alginate in the core plays a predominant role in determining the level of microcapsule colonization. This was confirmed by experiments showing reduced growth rates of batch suspension cultures of CHO cells in medium containing dissolved alginate. Removal of this alginate would therefore be expected to increase microcapsule colonization.     

海藻酸钠微胶囊制备及其在微生物包埋中的应用

海藻酸钠微胶囊作为一种包埋系统,因其价廉、无毒、生物相容性好、可生物降解等优点而备受关注.海藻酸钠微胶囊制备的研究一直是微胶囊制备的重要组成部分.本文概述了近年来海藻酸钠微胶囊的研究进展,包括主要制备方法及其影响因素,包埋微生物以改善微生物的应用性能等方面,并展望了海藻酸钠微胶囊在工业微生物等领域的发展.     

Preparation and application of poly(vinylamine)/alginate microcapsules to culturing of a mouse erythroleukemia cell line

Poly(vinylamine) was synthesized and used to replace poly-L-lysine in forming microcapsule with alginate. Test results indicated that capsules with good mechanical strength and permeability could be obtained under the controlled treatment conditions of poly(vinylamine) and alginate. Application of the current microcapsular system to cell culture was demonstrated by the usage of erythropoietin- (EPO-) producing IW32 mouse erythroleukemia cells. The encapsulated IW32 cells grew to a density of 8 x 10(7) cells/mL, two times that found in the corresponding poly-L-lysine/alginate capsules. The EPO accumulation inside the microcapsule with the current encapsulation system was also higher. A concentration of 7.3 U/mL was attained as compared to 4.3 U/mL in the poly-L-lysine/alginate microcapsule. (c) 1992 John Wiley & Sons, Inc.     

A novel cytomedical vehicle capable of protecting cells against complement

We have developed "Cytomedicine," which consists of functional cells entrapped in semipermeable polymer, and previously reported that APA microcapsules could protect the entrapped cells from injury by cellular immune system. However, microencapsulated cells were not protected from humoral immune system. Here, we developed a novel APA microcapsule, in which APA microbeads (APA(Ba) microbeads) were modified to contain a barium alginate hydrogel within their centers in an attempt to make it more difficult for antibody and complement to permeate the microcapsules. The permeability of APA(Ba) microbeads was clearly less than that of APA microcapsules, presumably due to the presence of barium alginate hydrogel. Cells encapsulated within APA(Ba) microbeads were protected against treatment with xenogeneic anti-serum. Furthermore, murine pancreatic beta-cells encapsulated in APA(Ba) microbeads remained viable and continued to secrete insulin in response to glucose. Therefore, APA(Ba) microbeads may be a useful carrier for developing anti-complement device for cytomedical therapy.     

海藻酸钠/壳聚糖微胶囊固定化大肠杆菌的研究

本文以大肠杆菌ＤＨ5α为模型体系 ,探索了大肠杆菌ＤＨ5α用海藻酸钠 壳聚糖 (ＡＣＡ)微胶囊培养的可行性 ,并观察了微囊化大肠杆菌ＤＨ5α细胞生长与物料渗透性能 ,通过将ＡＣＡ微胶囊移植到实验组小鼠体内 ,考察了ＡＣＡ微胶囊作为口服药物载体的可能性。1　材料和方法1.1　材料壳聚糖 ,本实验室改性所得 ;海藻酸钠 ,ＫｅｌｃｏＤｉｖｏｆＭｅｒ ｃｋＣｏ .Ｉｎｃ .ＵＳＡ ;其它试剂均为国产分析纯。大肠杆菌ＤＨ5α ,长春生物制品所 ;ＬＢ培养基 ,华美生物制品公司提供。昆明系小白鼠 18～ 2 0ｇ ,解放军大连高等医学专科学校实验动物中…     

APA微囊微环境影响胚胎干细胞增殖分化的体外研究

以小鼠胚胎T细胞（embryonic stem cell,ESC）为模型,在牛理条件F对ESC进行微囊化包封、培养,并利用免疫组织化学技术及RT-PCR方法检测其生长及未分化状态,以期建立微囊化ESC这一体外培养模型,同时明确海藻酸钠-聚赖氨酸-海藻酸钠（alginate-poly-lysine-alginate,APA）微囊微环境对ESC增殖及分化潜能的影响。结果表明：ESC能够在微囊（包括液化型及非液化型）或微球（海藻酸钙胶珠）内生长良好,但因生长环境存在差异,其表现的生长行为各具特征。比较其它类型,ESC在液化型APA微囊内的存活期限最长。经体外维持培养3周以上,仍能持续表达胚胎源未分化T细胞的标志性蛋白AP,SSEA-1及转录因子Oct-4。为进一步明确微囊内增殖的ESC是台仍具有多向分化的干细胞潜能,应用机械破囊法释放微囊内ESC团,并在体外进行定向诱导。经过近3周的条件诱导,其结果为：细胞团DTZ染色阳性：anti-insulin免疫荧光检测阳性;且特异性表达Pdx-1,Ins-1基因。上述结果证明：APA微囊为ESC维持未分化状态的增殖提供了特殊的微环境,APA微囊内所形成的ESC团仍具有多向分化的干细胞潜能。     

Production of cell-enclosing hollow-core agarose microcapsules via jetting in water-immiscible liquid paraffin and formation of embryoid body-like spherical tissues from mouse ES cells enclosed within these microcapsules

We developed agarose microcapsules with a single hollow core templated by alginate microparticles using a jet-technique. We extruded an agarose aqueous solution containing suspended alginate microparticles into a coflowing stream of liquid paraffin and controlled the diameter of the agarose microparticles by changing the flow rate of the liquid paraffin. Subsequent degradation of the inner alginate microparticles using alginate lyase resulted in the hollow-core structure. We successfully obtained agarose microcapsules with 20-50 microm of agarose gel layer thickness and hollow cores ranging in diameter from ca. 50 to 450 microm. Using alginate microparticles of ca. 150 microm in diameter and enclosing feline kidney cells, we were able to create cell-enclosing agarose microcapsules with a hollow core of ca. 150 microm in diameter. The cells in these microcapsules grew much faster than those in alginate microparticles. In addition, we enclosed mouse embryonic stem cells in agarose microcapsules. The embryonic stem cells began to self-aggregate in the core just after encapsulation, and subsequently grew and formed embryoid body-like spherical tissues in the hollow core of the microcapsules. These results show that our novel microcapsule production technique and the resultant microcapsules have potential for tissue engineering, cell therapy and biopharmaceutical applications.     

An improved method of microencapsulation and its evaluation to protect Lactobacillus spp. in simulated gastric conditions

An improved method of microencapsulation was developed to increase the efficacy of capsules in protecting the encapsulated bacteria under simulated gastric conditions. Lactobacillus acidophilus CSCC 2400 was encapsulated in calcium alginate and tested for its survival in simulated gastric conditions. The effects of different capsule sizes (200, 450, 1000 microm), different sodium alginate concentrations (0.75%, 1%, 1.5%, 1.8% and 2% w/v) and different concentrations of calcium chloride (0.1, 0.2, 1.0 M) on the viability of encapsulated bacteria were investigated. The viability of the cells in the microcapsules increased with an increase in alginate capsule size and gel concentration. There was no significant difference (p>0.05) in the viability of encapsulated cells when the concentration of calcium chloride was increased. Increase in cell load during encapsulation increased the number of bacterial survivors at the end of 3-h incubation in simulated gastric conditions. Hardening the capsule in calcium chloride solution for a longer time (8 h) had no impact on increasing the viability of encapsulated bacteria in a simulated gastric environment. The release of encapsulated cells at different phosphate buffer concentrations was also studied. When encapsulated L. acidophilus CSCC 2400 and L. acidophilus CSCC 2409 were subjected to low pH (pH 2) and high bile concentration (1.0% bile) under optimal encapsulation conditions (1.8% (w/v) alginate, 10(9) CFU/ml, 30 min hardening in 0.1 M CaCl(2) and capsule size 450 microm), there was a significant increase (p<0.05) in viable cell counts, compared to the free cells under similar conditions. Thus the encapsulation method described in this study may be effectively used to protect the lactobacillus from adverse gastric conditions.     

Sustained and therapeutic levels of human factor IX in hemophilia B mice implanted with microcapsules: key role of encapsulated cells

BACKGROUND: A gene therapy delivery system based on microcapsules enclosing recombinant cells engineered to secrete a therapeutic protein was explored in this study. In order to prevent immune rejection of the delivered cells, they were enclosed in non-antigenic biocompatible alginate microcapsules prior to being implanted intraperitoneally into mice. We have shown that encapsulated C2C12 myoblasts can temporarily deliver therapeutic levels of factor IX (FIX) in mice, but the C2C12 myoblasts elicited an immune response to FIX. In this study we report the use of mouse fetal G8 myoblasts secreting hFIX in hemophilia mice. METHODS: Mouse G8 myoblasts were transduced with MFG-FIX vector. A pool of recombinant G8 myoblasts secreting approximately 1500 ng hFIX/10(6) cells/24 h in vitro were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into immunocompetent C57BL/6 and hemophilic mice. RESULTS: Circulating levels of hFIX in treated mice reached approximately 400 ng/ml for at least 120 days (end of experiment). Interestingly, mice treated with encapsulated G8 myoblasts did not develop anti-hFIX antibodies. Activated partial thromboplastin time (APTT) of plasmas obtained from treated hemophilic mice was reduced from 107 to 82 sec on day 60 post-treatment, and whole blood clotting time (WBCT) was also corrected from 7-9 min before treatment to 3-5 min following microcapsule implantation. Further, mice were protected against bleeding following major trauma. Thus, the FIX delivery in vivo was biologically active. CONCLUSIONS: Our findings suggest that the type of cells encapsulated play a key role in the generation of immune responses against the transgene. Further, a judicious selection of encapsulated cells is critical for achieving sustained gene expression. Our findings support the feasibility of encapsulated G8 myoblasts as a gene therapy approach for hemophilia B.     

Alginate Microcapsule as a 3D Platform for Propagation and Differentiation of Human Embryonic Stem Cells (hESC) to Different Lineages

Human embryonic stem cells (hESC) are emerging as an attractive alternative source for cell replacement therapy since they can be expanded in culture indefinitely and differentiated to any cell types in the body. Various types of biomaterials have also been used in stem cell cultures to provide a microenvironment mimicking the stem cell niche^1-3. The latter is important for promoting cell-to-cell interaction, cell proliferation, and differentiation into specific lineages as well as tissue organization by providing a three-dimensional (3D) environment⁴ such as encapsulation. The principle of cell encapsulation involves entrapment of living cells within the confines of semi-permeable membranes in 3D cultures². These membranes allow for the exchange of nutrients, oxygen and stimuli across the membranes, whereas antibodies and immune cells from the host that are larger than the capsule pore size are excluded⁵. Here, we present an approach to culture and differentiate hESC DA neurons in a 3D microenvironment using alginate microcapsules. We have modified the culture conditions² to enhance the viability of encapsulated hESC. We have previously shown that the addition of p160-Rho-associated coiled-coil kinase (ROCK) inhibitor, Y-27632 and human fetal fibroblast-conditioned serum replacement medium (hFF-CM) to the 3D platform significantly enhanced the viability of encapsulated hESC in which the cells expressed definitive endoderm marker genes¹. We have now used this 3D platform for the propagation of hESC and efficient differentiation to DA neurons. Protein and gene expression analyses after the final stage of DA neuronal differentiation showed an increased expression of tyrosine hydroxylase (TH), a marker for DA neurons, >100 folds after 2 weeks. We hypothesized that our 3D platform using alginate microcapsules may be useful to study the proliferation and directed differentiation of hESC to various lineages. This 3D system also allows the separation of feeder cells from hESC during the process of differentiation and also has potential for immune-isolation during transplantation in the future.     

In vitro evaluation of the activity of microencapsulated carvacrol against Escherichia coli with K88 pili

Aims: The aim of the current study is to develop encapsulation of essential oils for oral delivery to the small intestine of pigs in order to retain their antimicrobial activity. Methods and Results: Carvacrol was used as a model essential oil and successfully encapsulated in microcapsules made from Ca‐alginate hydrogel using an emulsion–extrusion technology with high encapsulation efficiency. This encapsulation method did not compromise the antimicrobial activity when tested against Escherichia coli K88 in a culture medium, as well as in a simulated gastrointestinal model. In the simulated gastrointestinal model, <20% of encapsulated carvacrol was released in the simulated gastric fluid; the rest was nearly completely released in the intestinal fluid after 6 h of incubation. Conclusions: Encapsulation in Ca‐alginate microcapsules could effectively reduce the early absorption of carvacrol in the upper gastrointestinal tract after oral administration, therefore, retains its potential antibacterial activity for the small intestine. Significance and Impact of the Study: The developed encapsulation method is expected to be suitable for encapsulation of other essential oils. The results from this study would increase the likelihood of success in the application of essential oils as antimicrobial agents for controlling enteric diseases in pigs.     

Influence of microenvironmental conditions on hybridoma cell growth inside the alginate-poly-l-lysine microcapsule

A mathematical model was formulated to describe hybridoma cell growth within the alginate-poly-l-lysine (alginate-PLL) microcapsules during air-lift bioreactor cultivation. Model development was based on experimentally obtained data concerning the hybridoma cell counts, monoclonal antibody (mAb) production and the distribution of hybridoma cell growth within the microcapsules. The cell growth was modeled using a mean field approach expressed as Langevin class of equations for two different regions of alginate-PLL microcapsules, the alginate microcapsule core and the annular region between microcapsule core and membrane. In this paper we propose an influence of microenvironmental conditions on cell growth. The osmotic pressure changes in the Na-alginate liquefied annular region, as well as, the resistance effects of Ca-alginate hydrogel in the core region during the cell growth were incorporated into the model. Good agreement between the experimental data and model prediction values was obtained. The proposed model successfully predicted the impact of various microenvironmental restriction effects on the dynamics of cell growth and appears useful for further optimization of microcapsule design in order to achieve higher intra-capsule cell concentrations resulting in higher amounts of mAb produced.     

Process optimization for microencapsulation of probiotic yeasts

Background

Microencapsulation is a technique which improves the survival and viability of probiotics. We demonstrate encapsulation of five potential probiotic yeasts with alginate and gum as encapsulation matrices to improve their gastrointestinal transit.

Methods

Gum extracted from various cereals viz. rice, oats, barley, finger millet and pearl millet along with alginate have been used to encapsulate five potential probiotic yeasts. Screening was carried out by measuring swelling index, encapsulation efficiency and nutritional value of microcapsules encapsulated with alginate and gum. The concentration of OBG, sodium alginate and inoculum dosage of probiotic yeasts was optimized using response surface methodology (RSM). Efficiency of alginate OBG microcapsules with or without coating materials viz. whey protein and chitosan also tested. The mucoadhesion ability and storage stability of alginate OBG microcapsules with coating materials were tested.

Results

Highest encapsulation efficiency of probiotic yeasts was noted using oats bran gum (OBG) microcapsules along with alginate in all the five probiotic yeasts. Notably whey protein coated microcapsules showed maximum GIT tolerance (95%) and mucoadhesion (90%) for L. starkeyi VIT-MN03. The minimum loss of viability was observed in L. starkeyi VITMN03 microcapsules on 60th day of storage.

Conclusions

This is the first report on optimization and survival of microencapsulated probiotic yeasts under simulated GIT conditions using natural gum and alginate as encapsulation matrices and whey protein as coating material.

     

Synthesis,characterization and preliminary analysis of in vivo biological activity of chitosan/celecoxib microcapsules

The use of chitosan as the wall of microcapsule designed for delivery of encapsulated celecoxib is reported. Microcapsules were characterised with respect to size and encapsulation efficiency of celecoxib. In vivo animals demonstrated that both free celecoxib administration and chitosan/celecoxib microcapsules administration lead to a significant inhibition of cyclooxygenase-2 protein expression in the hepatocytes when compared with vehicle control mice. Interestingly, microcapsule containing celecoxib showed a better inhibition of cyclooxygenase-2 protein expression when compared with a simple oral administration of free celecoxib. Gas-chromatography–mass-spectrometry analysis showed that in mice treated with free celecoxib or chitosan/celecoxib microcapsules, their plasma concentration of celecoxib was similar. Microcapsules-based biomaterials as oral drug delivery vehicles may help to improve the absorption efficiency of therapeutic drugs.