Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract

Abstract

Microcapsules containing insulin were prepared using a combination of a W/O/W double emulsion and complex coacervation between WPI (used as a hydrophilic emulsifier) and CMC or SA with further spray drying of the microcapsules in order to provide protection in the gastrointestinal tract. The microcapsules prepared exhibited high encapsulation efficiency and showed the typical structure of a double emulsion. After spray drying of these microcapsules, the integrity of the W/O/W double emulsion was maintained and the biological residual activity remained high when using the combination of 180?°C inlet air temperature and 70?°C outlet air temperature. The microcapsules exhibited low solubility at pH 2 and high solubility at pH 7 so they might protect insulin at acid pH values in the stomach and release it at intestinal pH values. The microcapsules developed in this study seem to be a promising oral delivery vehicle for insulin or other therapeutic proteins.     

Microencapsulation of Theobroma cacao L. waste extract: optimization using response surface methodology

The cocoa extract (Theobroma cacao L.) has a significant amount of polyphenols (TP) with potent antioxidant activity (AA). This study aims to optimise microencapsulation of the extract of cocoa waste using chitosan and maltodextrin. Microencapsulation tests were performed according to a Box–Behnken factorial design, and the results were evaluated by response surface methodology with temperature, maltodextrin concentration (MD) and extract flowrate (EF) as independent variables, and the fraction of encapsulated TP, TP encapsulation yield, AA, yield of drying and solubility index as responses. The optimum conditions were: inlet temperature of 170?°C, MD of 5% and EF of 2.5?mL/min. HPLC analysis identified epicatechin as the major component of both the extract and microparticles. TP release was faster at pH 3.5 than in water. These results as a whole suggest that microencapsulation was successful and the final product can be used as a nutrient source for aquatic animal feed.

• Highlights

• Microencapsulation is optimised according to a factorial design of the Box–Behnken type.

• Epicatechin is the major component of both the extract and microcapsules.

• The release of polyphenols from microcapsules is faster at pH 3.5 than in water.

     

Production of BSA-loaded alginate microcapsules: Influence of spray dryer parameters on the microcapsule characteristics and BSA release

The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1?N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3?bar compared to 4?bar and with a feed rate of 0.45 vs. 0.2?ml?s^?1. A high feed rate (0.45 vs. 0.2?ml?s^?1) allows one to obtain microcapsules with a low BSA release (p?=?0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p?=?0.0230). A higher air pressure of 4?bar compared to 3?bar resulted in a lower microcapsule size (2.55 vs. 2.80?µm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.     

Production of BSA-loaded alginate microcapsules: Influence of spray dryer parameters on the microcapsule characteristics and BSA release

The aim of this study was to optimize the production of BSA-loaded alginate microcapsules by spray drying and to study the release of bovine serum albumin fraction V (BSA) under gastric simulated conditions. Microcapsule yield, BSA release, microcapsule size and size distribution were characterized following the application of different production parameters including inlet air temperature, inlet air pressure and liquid feed rate. The microcapsules were incubated in 0.1?N HCl and BSA release was quantified over time. The yields were higher with the pressure of 3?bar compared to 4?bar and with a feed rate of 0.45 vs. 0.2?ml s^?1. A high feed rate (0.45 vs. 0.2?ml s^?1) allows one to obtain microcapsules with a low BSA release (p?=?0.0327). The increase of the atomizer inlet temperature leads to microcapsules with a higher BSA release (p?=?0.0230). A higher air pressure of 4?bar compared to 3?bar resulted in a lower microcapsule size (2.55 vs. 2.80?µm) and led to a narrower size distribution (0.92 vs. 1.07). In conclusion, the spray dryer parameters influenced the alginate microcapsule characteristics as well as subsequent protein release into a simulated gastric medium.     

Preparation optimisation and storage stability of nanoemulsion-based lutein delivery systems

Abstract

The present work formed lutein-enriched nanoemulsions stabilised by sodium caseinate (SC) using a high-pressure homogenisation process, and the influence of environmental conditions on the physicochemical stability of the nanoemulsion was investigated. The results showed that the droplet diameter of the nanoemulsion was largely dependent on homogenisation conditions. Optimum results were obtained for 1.0% (w/w) SC, 100?MPa pressure, and 7 homogenisation cycles, which produced a nanoemulsion with a mean droplet diameter of 234.01?±?3.40?nm, polydispersity index of 0.123?±?0.028, and zeta potential of ?36.56?±?1.51?mV. The nanoemulsion remained physically stable after a 30 d storage at 4?°C, and the chemical degradation rate of lutein was considerably decreased. Thermal treatment at 60–100?°C had little effect on its physicochemical stability; conversely, pH, ionic strength (NaCl or CaCl₂), concentration treatment, and freeze–thaw cycling had major impacts on the physicochemical stability of nanoemulsion.     

Effects of lipid formulations on clove extract spray dried powders: comparison of physicochemical properties,storage stability and in vitro intestinal permeation

Abstract

Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove’s bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25?°C and 40?°C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.     

不同提取方法GC-MS分析结合保留指数定性木香挥发性成分

目的 分析比较不同采集方法制备的木香挥发性成分。 方法 分别采用水蒸气蒸馏法和顶空加热提取挥发性成分的方法,对其进行气相色谱-质谱(GC-MS)结合保留指数双重定性。 结果 可鉴定出顶空进样的木香中42个挥发性化学成分;可鉴定出水蒸气蒸馏法提取的32个挥发性化学成分;两种采样方法进行的GC-MS分析,有14种相同化合物,但相对含量有一定差异。 结论 两种采样方法,分别提供了木香中不同沸点的挥发性成分的化学信息;运用这两种方法可以建立更全面的木香挥发性成分GC-MS表征体系。     

Evaluation of the anticancer activity of sprout extract-loaded nanoemulsion of N. sativa against hepatocellular carcinoma

Abstract

Nigella sativa L. belonging to Ranunculaceae family is an important medicinal spice which has been utilised to treat various chronic diseases. Lipid nanoemulsions containing oil from medicinal plants have shown to enhance drug dissolvability, diminish symptoms of different powerful medications and enhance the bioavailability of medications, in contrast with conventional formulations. In the present study, aqueous titration method was used to prepare nanoemulsion. The optimised formulation (NE₁₁) with the mean particle size of 37.47?nm showed a minimum viscosity of 0.547 cps and maximum drug release (98.2%) in 24?h. The stability study showed considerably stable formulations at refrigerator temperature as compared to room temperature. The cancer cell line studies confirmed that 5d sprout extract of N. sativa nanoemulsion reduced the cell viability (p?<?.05) and increased colony formation, ROS intensity and chromatin condensation. All data such as colony formation, ROS intensity and chromatin condensation are represented as mean?±?SD (p?<?.001) treated cells for 48?hours. Our results concluded that the development of nanoemulsion could be an efficient carrier for drug delivery.     

The effect of molecular weights of microencapsulating polymers on viability of mouse-cloned pancreatic β-cells: biomaterials,osmotic forces and potential applications in diabetes treatment

Introduction: Ideal cell-containing microcapsules should be capable of maintaining cell viability and exhibit significant structural stability to support cellular functionality. To date, such microcapsules remain unavailable; thus, this study used our well-established microencapsulating methods to examine a total of 32 different microencapsulating formulations and correlate polymers’ molecular weights (M_wt) and UDCA addition, with cell viability and microcapsules’ stability, postmicroencapsulation.

Methods: MIN6 mouse-cloned pancreatic β-cells were microencapsulated using control (n?=?16; without UDCA) and test (n?=?16; with UDCA) different polymers. Confocal microscopic imaging, cell viability, and microcapsules’ stability were assessed.

Results: Best cell viability (>50%) was obtained at average M_wt of 50,000?g/mol (poly-l-ornithine), followed by 110,000?g/mol (poly-l-lysine). There was no linear correlation between M_wt and viability. Confocal imagining showed similar microcapsules’ shape and cell distribution among all different polymers’ molecular weights, which suggests that the microencapsulating method was efficient and maintained microcapsules’ uniformity. UDCA addition resulted in enhanced osmotic stability of the microcapsules and improved cell viability, when the formulation contained 1% polylornithine, 1% polyethylene glycol, 20% Eudragit^® NM30D, 1% polytetrafluoroethylene, or 5% pentamethylcyclopentasiloxane.

Conclusions: UDCA addition improved microenvironmental conditions within the microcapsules but this effect was largely dependent on the polymer systems used.     

Microencapsulation by spray drying of lemon essential oil: Evaluation of mixtures of mesquite gum–nopal mucilage as new wall materials

Mesquite gum (MG) and nopal mucilage (NM) mixtures were used for microencapsulation of lemon essential oil (LEO) by spray drying. Emulsions of MG, NM and MG–NM mixtures (25–75, 50–50, 75–25) were evaluated according to the droplet size (1.49–9.16?μm), viscosity and zeta potential (?16.07 to ?20.13?mV), and microcapsules were characterised in particle size (11.9–44.4?μm), morphology, volatile oil retention (VOR) (45.9–74.4%), encapsulation efficiency (EE) (70.9–90.6%), oxidative stability and thermal analysis. The higher concentration of MG led to smaller droplet sizes and lower viscosity in the emulsions, and smaller particle sizes with the highest VOR in microcapsules. The higher concentration of NM induced to higher viscosity in the emulsions, and larger particle sizes with the highest values of EE and oxidative stability in microcapsules. This work shows evidence that MG–NM mixtures can have synergic effect in desirable characteristics such as retention and shelf life extension of LEO in microcapsules.     

Soy extract and maltodextrin as microencapsulating agents for Lactobacillus acidophilus: a model approach

Abstract

The present study aimed to optimise the microencapsulation of Lactobacillus acidophilus La-05 by spray drying, using soy extract and maltodextrin as encapsulants. Air inlet temperature, maltodextrin/soy extract ratio and feed flow rate were investigated through Central Composite Rotational Design (CCRD). Probiotic viability increased with increasing the proportion of soy extract. Temperature and feed flow rate had a negative effect. Particle diameter ranged from 4.97 to 8.82?μm, water activity from 0.25 to 0.52 and moisture from 2.30 to 7.01?g.100g^?1 Particles produced following the optimised conditions (air temperature of 87?°C, maltodextrin/soy extract ratio of 2:3 w.w^?1, feed flow rate of 0.54?L.h^?1) reached Encapsulation yield (EY) of 83%. Thermogravimetry and FTIR analysis suggested that microcapsules could protect L. acidophilus cells against dehydration and heating. During storage, microencapsulated probiotic had high cell viability (reductions ranged between 0.12 and 1.72 log cycles). Soy extract/maltodextrin presented well-encapsulating properties of Lactobacillus acidophilus La-05.     

Development and in vivo evaluation of baicalin-loaded W/O nanoemulsion for lymphatic absorption

Background: Lymphatic formations that effectively eradicate the virus in the lymphatic system will be therapeutically advantagous in hepatitis B virus (HBV) infection. Lipid-based formulation is often used to deliver drug via the lymphatic system. Baicalin nanoemulsion may be a promising drug delivery system for improved treatment of HBV infection.

Objective: This study aimed to prepare, characterize, and evaluate a lipid-based nanoemulsion containing baicalin for lymphatic system absorption.

Method: The presence of a nanoemulsion region was studied by pseudoternary phase diagrams. The physicochemical properties of a baicalin-loaded nanoemulsion were investigated. The oral bioavailability of the baicalin-loaded nanoemulsion was compared to that of a baicalin suspension. A chylomicron flow blocking model was used to examine the extent of lymphatic uptake. The lymph node distribution of baicalin was measured to investigate the lymphatic transport ability of the nanoemulsion compared to the suspension.

Results: Compared to the baicalin suspension, the AUC_0-t and C_max values of the baicalin nanoemulsion were increased by 10.5-fold and 3.12-fold, respectively. Compared with the saline-treated rats that were orally administered the baicalin nanoemulsion, the AUC_0-t and C_max values of the nanoemulsion for the rats pretreated with cycloheximide were reduced from 23.076?±?1.244?mg/L h to 9.236?±?0.940?mg/L h and from 3.010?±?0.119?mg/L to 1.567?±?0.220?mg/L, respectively. In comparing baicalin in W/O nanoemulsion with suspension, the C_max value was found to be 11.5-fold higher in the lymph nodes of the rats treated with the nanoemulsion.

Conclusion: The results indicated that a baicalin-loaded W/O nanoemulsion may be a promising drug delivery system for the treatment of chronic hepatitis B.     

Chokeberry polyphenols preservation using spray drying: effect of encapsulation using maltodextrin and skimmed milk on their recovery following in vitro digestion

Abstract

Aim: Microencapsulation of chokeberry extracts was performed in order to improve functionality, stability, and bioavailability of extracted polyphenols.

Methods: Chokeberry fruits and juice by-product (waste) extracts were spray-dried by using two carriers, maltodextrin and skimmed milk. Morphological and physicochemical characteristics of the obtained powders were analysed. In vitro simulated digestion model was used as an indicator of polyphenolics bioavailability.

Results: The moisture content varied between 3.39 and 4.61%, zeta potential had negative values (35–39?mV), maltodetrin powders were smaller (4.27–5.12?µm) compared to skimmed ones (8.50–11.01?µm). All microparticles exhibited high encapsulation efficiency of total polyphenols and anthocyanins (73–97% and 63–96%, respectively). For both extract types, maltodextrin powders released higher phenolics content compared to skimmed milk. During in vitro digestion, maltodextrin exhibited a higher protective effect on both active compounds.

Conclusion: Taking into account the obtained results, chokeberry polyphenols stability might be improved using spray drying technique, and maltodextrin showed better properties.     

Microencapsulation of blackberry pulp with arrowroot starch and gum arabic mixture by spray drying

Abstract

This research work aimed to obtain blackberry pulp powder by spray drying and, by an experimental design, evaluated the effect of inlet air temperature (100–150?°C) and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2 on the physicochemical properties of the powders. Arrowroot starch and gum arabic present glass transition temperature (Tg) values above 100?°C; hence it was possible to employ them as carriers in blackberry pulp spray drying in order to increase Tg of the system. Powder yield and solubility increased with increasing blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:0.5–1:2, whereas hygroscopicity decreased. Yield, solubility and hygroscopicity of the powders increased and water activity decreased, with increasing inlet air temperature. The powders presented low moisture content and water activity. Temperature of 143?°C and blackberry pulp solids:arrowroot starch/gum arabic solids ratio of 1:1.78 were the optimal conditions to obtain high yield and blackberry powders that are soluble in water and less hygroscopic.     

Design and evaluation of oral nanoemulsion drug delivery system of mebudipine

Abstract

A nanoemulsion drug delivery system was developed to increase the oral bioavailability of mebudipine as a calcium channel blocker with very low bioavailability profile. The impact of nano-formulation on the pharmacokinetic parameters of mebudipine in rats was investigated. Nanoemulsion formulations containing ethyl oleate, Tween 80, Span 80, polyethylene glycol 400, ethanol and deionized water were prepared using probe sonicator. The optimum formulation was evaluated for physicochemical properties, such as particle size, morphology and stability. The particle size of optimum formulation was 22.8?±?4.0?nm. Based on the results of this study, the relative bioavailability of mebudipine nanoemulsion was enhanced by about 2.6-, 2.0- and 1.9-fold, respectively, compared with suspension, ethyl oleate solution and micellar solution. In conclusion, nanoemulsion is an interesting option for the delivery of poorly water soluble molecules, such as mebudipine.     

桂枝、当归挥发油微囊处方优化及体内药动学研究

目的 优化桂枝、当归挥发油微囊的处方,对处方优化后制备的微囊进行相关表征和大鼠体内药动学研究。方法 采用喷雾干燥法制备桂枝、当归挥发油微囊。以载药量和包封率为指标,通过Box-Behnken设计-效应面法优化处方。采用傅里叶变换红外光谱和扫描电镜方法对处方优化后制备的微囊进行表征。按照100 mg·kg^-1的剂量灌胃给药后采血,HPLC测定血药浓度,比较体内药动学行为。结果 最佳处方为芯材-囊材比1∶1.7,囊材浓度为10.25%,复合囊材辛烯基琥珀酸淀粉钠/麦芽糊精比为3.8∶1,高压均质压力为20 MPa,喷雾干燥进口温度为185 ℃。在该条件下,测得微囊的载药量为(18.94±1.09)%,包封率(96.03±2.91)%。傅里叶变换红外光谱和扫描电镜结果表明,挥发油已成功被包覆在囊壁材料中,微囊基本形状为球形,表面凹陷但无明显裂缝。体内药动学结果显示,微囊组的达峰时间(t_max)、半衰期(t_1/2)、清除率(CL)、时间-曲线下面积(AUC_0-t)、药物从中央室消除的一级速率常数(k₁₀)、药物从中央室向周边室转运的一级速率常数(k₁₂)、药物从周边室向中央室转运的一级速率常数(k₂₁)等药动学参数与挥发油组的差异均具有统计学意义(P<0.05或P<0.01)。药动学结果表明微囊有效延长了桂枝、当归挥发油在体内滞留时间,促进药物在体内的吸收,口服相对生物利用度提高至2.62倍。结论 Box-Behnken设计-效应面法所建立的模型能较好地优化桂枝、当归挥发油微囊的处方工艺,具有良好预测性。处方优化后制备的微囊具有良好载药性能,提高了挥发油的生物利用度。     

不同干燥方式对颗粒粉体性质的影响

目的 探究不同干燥方式对颗粒粉体性质的影响。方法 采用相同的处方进行制粒,采用真空干燥,烘箱干燥及流化床干燥,测定不同干燥方式所得颗粒的流动性指数,综合评价不同干燥方式所得颗粒的粉体性质。结果 三者中烘箱干燥产物的流动性最好,可压性无明显区别。结论 不同干燥工艺造成了干燥产物粉体性质的差异。     

气相色谱-质谱法结合保留指数分析鸭儿芹不同部位挥发油成分

目的 研究鸭儿芹不同部位挥发油成分的差异。方法 采用水蒸气蒸馏法提取鸭儿芹根、茎、叶、果实中的挥发油,对其进行气相色谱-质谱法(GC-MS)分析,并结合Kovats保留指数对其主要成分进行定性分析。结果 鸭儿芹根挥发油检出28个峰,鉴定出28个化合物,占总离子峰的86.66%;鸭儿芹茎挥发油检出27个峰,鉴定出27个化合物,占总离子峰的88.01%;鸭儿芹叶挥发油检出27个峰,鉴定出27个化合物,占总离子峰的94.03%;鸭儿芹果实挥发油检出26个峰,鉴定出26个化合物,占总离子峰的88.32%。鸭儿芹全株共鉴定出35种挥发性化合物,各部位挥发油的主要成分为倍半萜化合物,含有少量的单萜。其中22种化合物为各部位共有,化合物19、23只存在鸭儿芹根挥发油,香树烯、化合物25、红没药醇只存在鸭儿芹果实挥发油,因此它们的种类及相同化合物的含量有一定差异。结论 鸭儿芹挥发油含有多种生理活性物质,全草入药有其合理性,为进一步研究开发鸭儿芹提供一定的科学依据。     

Effect of wall material on the antioxidant activity and physicochemical properties of Rubus fruticosus juice microcapsules

Abstract

Blackberry (Rubus fruticosus) juice possesses compounds with antioxidant activity, which can be protected by different biopolymers used in the microencapsulation. Therefore, the effects of cell wall material including maltodextrin (MD), Arabic gum (GA) and whey protein concentrate (WPC) were evaluated on the physicochemical and antioxidant properties of encapsulated blackberries using a spray-drying technique. Anthocyanin concentration, polymeric colour, total polyphenols, radical scavenging activity of the 1,1-diphenyl-2-picrilhydrazil radical, reducing power and the stability at different storage conditions were evaluated. GA and MD conferred a similar protection to the antioxidant compounds when the microcapsules were stored at low water activities (a_w?<?0.515) in contrast to at a high moisture content (a_w?>?0.902), whereas WPC presented a high protection. Therefore, the selection of the best wall material for blackberry juice encapsulation depends of the conditions of storage of the powder.     

Application of encapsulated natural bioactive compounds from red pepper waste in yogurt

Abstract

Aim: The aim of this study was to encapsulate red pepper waste (RPW) bioactives and monitor their stability in yogurt.

Methods: RPW extract was encapsulated in whey protein using spray and freeze-drying techniques. Physicochemical characteristics of encapsulates were evaluated, and better encapsulates were used to develop functional yogurt. Retention of bioactives was followed over 21?days of storage, and sensory analyses were assessed.

Results: Freeze-dried encapsulates (FDE) showed better characteristics like water activity, moisture content, solubility, flowing and colour properties, and, therefore, incorporated in yogurt. Yogurt with FDE successfully retained carotenoids (71.43%) and caused increasing of polyphenol retention (up to 123.73%). This yogurt exhibited higher sensory and general acceptability scores compared to control sample. The fortification of yogurts had a positive influence on maintaining the initial number of lactic acid bacteria during storage.

Conclusion: Freeze drying and utilisation of pepper waste are efficient for functional food development, with improved nutritional, colour and bioactive properties.